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Sample records for enzyme ace gene

  1. The angiotensin-converting enzyme (ACE) gene family of Bombyx mori.

    PubMed

    Yan, Hai-Yan; Mita, Kazuei; Zhao, Xia; Tanaka, Yoshikazu; Moriyama, Minoru; Wang, Huabin; Iwanaga, Masashi; Kawasaki, Hideki

    2017-04-15

    We previously reported regarding an ecdysone-inducible angiotensin-converting enzyme (ACE) gene. We found another four ACE genes in the Bombyx genome. The present study was undertaken to clarify the evolutionally changed function of the ACE of Bombyx mori. Core regions of deduced amino acid sequences of ACE genes were compared with those of other insect ACE genes. Five Bombyx genes have the conserved Zn(2+)-binding-site motif (HEXXH); however, BmAcer4 has only one and BmAcer3 has no catalytic ligand. BmAcer1 and BmAcer2 were expressed in several organs. BmAcer3 was expressed in testes, and BmAcer4 and BmAcer5 were expressed in compound eyes; however, the transcription levels of these three genes were very low. Quantitative RT-PCR and Western analysis were conducted to determine the tissue distribution and developmental expression of BmAcer1and BmAcer2. Transcripts of BmAcer1 and BmAcer2 were found in the reproductive organs during the larval and pupal stages. BmAcer1 was dominant in fat bodies during the feeding stage and showed high expression in the epidermis, wing discs, and pupal wing tissues after the wandering stage. Its expression patterns in epidermis, wing discs, and wing tissues resembled the hemolymph ecdysteroid titer in the larval and pupal stages. Acer1 was observed in the hemolymph at all stages, appearing to be the source of it are fat bodies, wings, and epidermis, and functioning after being secreted into the hemolymph. BmAcer2 was abundant in the midgut during the feeding stage and after the wandering stage and in silk glands after the pupal stage. We conclude that the evolution of BmAcer occurred through duplication, and, thereafter, functional diversification developed.

  2. Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels.

    PubMed Central

    Tiret, L; Rigat, B; Visvikis, S; Breda, C; Corvol, P; Cambien, F; Soubrier, F

    1992-01-01

    The hypothesis of a genetic control of plasma angiotensin I-converting enzyme (ACE) level has been suggested both by segregation analysis and by the identification of an insertion/deletion (I/D) polymorphism of the ACE gene, a polymorphism contributing much to the variability of ACE level. To elucidate whether the I/D polymorphism was directly involved in the genetic regulation, plasma ACE activity and genotype for the I/D polymorphism were both measured in a sample of 98 healthy nuclear families. The pattern of familial correlations of ACE level was compatible with a zero correlation between spouses and equal parent-offspring and sib-sib correlations (.24 +/- .04). A segregation analysis indicated that this familial resemblance could be entirely explained by the transmission of a codominant major gene. The I/D polymorphism was associated with marked differences of ACE levels, although these differences were less pronounced than those observed in the segregation analysis. After adjustment for the polymorphism effects, the residual heritability (.280 +/- .096) was significant. Finally, a combined segregation and linkage analysis provided evidence that the major-gene effect was due to a variant of the ACE gene, in strong linkage disequilibrium with the I/D polymorphism. The marker allele I appeared always associated with the major-gene allele s characterized by lower ACE levels. The frequency of allele I was .431 +/- .025, and that of major allele s was .557 +/- .041. The major gene had codominant effects equal to 1.3 residual SDs and accounted for 44% of the total variability of ACE level, as compared with 28% for the I/D polymorphism.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:1319114

  3. High association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with recurrent aphthous stomatitis.

    PubMed

    Karakus, Nevin; Yigit, Serbulent; Kalkan, Goknur; Sezer, Saime

    2013-08-01

    Recurrent aphthous stomatitis (RAS) is a common ulcerative disease of the oral mucosa. Oral ulcers are also the most common feature of Behçet's disease (BD). Association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with BD has been reported in Turkish population. The aim of the present study was to investigate the possible association between ACE gene I/D polymorphism and RAS, and evaluate if there was an association with clinical features in a relatively large cohort of Turkish patients. The study included 198 patients affected by RAS and 214 healthy controls. ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction with I and D allele-specific primers. The genotype and allele frequencies of I/D polymorphism showed statistically significant differences between RAS patients and controls (p < 0.0001 and p < 0.0001, respectively). After stratifying RAS patients according to clinical and demographical characteristics, no significant association was observed. In conclusion, the results of this study suggest that I/D polymorphism of the ACE gene was positively associated with predisposition to develop RAS in Turkish population. Further studies with larger populations are recommended.

  4. Angiotensin-converting enzyme (ACE) gene polymorphisms are associated with idiopathic pulmonary fibrosis.

    PubMed

    Uh, Soo-Taek; Kim, Tae-Hoon; Shim, Eun-Young; Jang, An-Soo; Park, Sung-Woo; Park, Jong-Sook; Park, Byung-Lae; Choi, Byoung Whui; Shin, Hyoung Doo; Kim, Dong Soon; Park, Choon-Sik

    2013-08-01

    Idiopathic pulmonary fibrosis (IPF) is characterized by progressive dyspnea and worsening lung function. ACE is increased in the bronchoalveolar lavage fluid from patients with IPF, suggesting the role of ACE in the pathogenesis of IPF. We evaluated the role of single-nucleotide polymorphisms (SNPs) in the development risk of IPF. Two-hundred twenty patients with IPF and 456 healthy subjects were included in this study. Eleven polymorphisms were selected among those reported previously. Genotype was performed by single base extension. Although absolute LD (|D'|= 1 and r(2 )= 1) was not present, 11 SNPs showed tight LDs. The logistic analysis of the all of 11 SNPs on the ACE genes between patients with IPF and healthy subjects were found to be related with the risk of IPF in recessive type. However, in patients with IPF diagnosed by surgical lung biopsy, only two SNP of -5538T>C and +21288_insdel SNPs were related with the risk of IPF in co-dominant type, and there were no SNPs related with the risk of IPF in dominant type. In patients with IPF diagnosed by clinical criteria or surgical lung biopsy, four SNPs on promoter (-5538T>C, -5508A>C, -3927T>C, -115T>C), one on intron (+15276A>G), one on exon (+21181G>A), and one in three prime region (+21288_insdel) were related with the risk of IPF. This study showed a newly discovered SNP of ACE associated with the risk of development of IPF. ACE -5538T>C and -5508A>C significantly associated with risk of IPF in Korea.

  5. Angiotensin-converting enzyme (ACE) gene insertion/deletion polymorphism is not a risk factor for hypertension in SLE nephritis.

    PubMed

    Negi, Vir S; Devaraju, Panneer; Gulati, Reena

    2015-09-01

    SLE is a systemic autoimmune disease with high prevalence of hypertension. Around 40-75 % of SLE patients develop nephritis, a major cause of hypertension and mortality. Angiotensin-converting enzyme (ACE) maintains the blood pressure and blood volume homeostasis. An insertion/deletion (I/D) polymorphism in intron 16 of ACE gene was reported to influence the development of hypertension, nephritis, and cardiovascular diseases in different ethnic populations. Despite compelling evidence for the high prevalence of hypertension in individuals with SLE, underlying factors for its development are not well studied. With this background, we analyzed the influence of ACE insertion/deletion polymorphism on susceptibility to SLE, development of nephritis and hypertension, other clinical features and autoantibody phenotype in South Indian SLE patients. Three hundred patients with SLE and 460 age and sex similar ethnicity matched individuals were included as patients and healthy controls, respectively. The ACE gene insertion/deletion polymorphism was analyzed by PCR. Insertion (I) and deletion (D) alleles were observed to be equally distributed among patients (57 and 43 %) and controls (59 and 41 %), respectively. The mutant (D) allele did not confer significant risk for SLE (II vs. ID: p = 0.4, OR 1.15, 95 % CI 0.8-1.6; II vs. DD: p = 0.34, OR 1.22, 95 % CI 0.8-1.85). There was no association of the ACE genotype or the allele with development of lupus nephritis (II vs. ID: p = 0.19, OR 1.41, 95 % CI 0.84-2.36; II vs. DD: p = 0.41, OR 0.74, 95 % CI 0.38-1.41) or hypertension (II vs. ID: p = 0.85, OR 0.9, 95 % CI 0.43-1.8; II vs. DD: p = 0.66, OR 1.217, 95 % CI 0.5-2.8). The presence of mutant allele (D) was not found to influence any clinical features or autoantibody phenotype. The insertion/deletion polymorphism of the ACE gene is not a genetic risk factor for SLE and does not influence development of hypertension or lupus nephritis in South Indian

  6. Identification of new polymorphisms of the angiotensin I-converting enzyme (ACE) gene, and study of their relationship to plasma ACE levels by two-QTL segregation-linkage analysis.

    PubMed Central

    Villard, E.; Tiret, L.; Visvikis, S.; Rakotovao, R.; Cambien, F.; Soubrier, F.

    1996-01-01

    Plasma angiotensin I-converting enzyme (ACE) levels are highly genetically determined. A previous segregation-linkage analysis suggested the existence of a functional mutation located within or close to the ACE locus, in almost complete linkage desequilibrium (LD) with the ACE insertion/deletion (I/D) polymorphism and accounting for half the ACE variance. In order to identify the functional variant at the molecular level, we compared ACE gene sequences between four subjects selected for having contrasted ACE levels and I/D genotypes. We identified 10 new polymorphisms, among which 8 were genotyped in 95 healthy nuclear families, in addition to the I/D polymorphism. These polymorphisms could be divided into two groups: five polymorphisms in the 5' region and three in the coding sequence and the 3' UTR. Within each group, polymorphisms were in nearly complete association, whereas polymorphisms from the two groups were in strong negative LD. After adjustment for the I/D polymorphism, all polymorphisms of the 5' group remained significantly associated with ACE levels, which suggests the existence of two quantitative trait loci (QTL) acting additively on ACE levels. Segregation-linkage analyses including one or two ACE-linked QTLs in LD with two ACE markers were performed to test this hypothesis. The two QTLs and the two markers were assumed to be in complete LD. Results supported the existence of two ACE-linked QTLs, which would explain 38% and 49% of the ACE variance in parents and offspring, respectively. One of these QTLs might be the I/D polymorphism itself or the newly characterized 4656(CT)2/3 polymorphism. The second QTL would have a frequency of approximately .20, which is incompatible with any of the yet-identified polymorphisms. More extensive sequencing and extended analyses in larger samples and in other populations will be necessary to characterize definitely the functional variants. PMID:8651305

  7. Angiotensin-converting enzyme (ACE) dimerization is the initial step in the ACE inhibitor-induced ACE signaling cascade in endothelial cells.

    PubMed

    Kohlstedt, Karin; Gershome, Cynthia; Friedrich, Matthias; Müller-Esterl, Werner; Alhenc-Gelas, François; Busse, Rudi; Fleming, Ingrid

    2006-05-01

    The binding of angiotensin-converting enzyme (ACE) inhibitors to ACE initiates a signaling cascade that involves the phosphorylation of the enzyme on Ser1270 as well as activation of the c-Jun NH2-terminal kinase (JNK) and leads to alterations in gene expression. To clarify how ACE inhibitors activate this pathway, we determined their effect on the ability of the enzyme to dimerize and the role of ACE dimerization in the initiation of the ACE signaling cascade. In endothelial cells, ACE was detected as a monomer as well as a dimer in native gel electrophoresis and dimerization/oligomerization was confirmed using the split-ubiquitin assay in yeast. ACE inhibitors elicited a rapid, concentration-dependent increase in the dimer/monomer ratio that correlated with that of the ACE inhibitorinduced phosphorylation of ACE. Cell treatment with galactose and glucose to prevent the putative lectin-mediated self-association of ACE or with specific antibodies shielding the N terminus of ACE failed to affect either the basal or the ACE inhibitor-induced dimerization of the enzyme. In ACE-expressing Chinese hamster ovary cells, ACE inhibitors elicited ACE dimerization and phosphorylation as well as the activation of JNK with similar kinetics to those observed in endothelial cells. However, these effects were prevented by the mutation of the essential Zn2+-complexing histidines in the C-terminal active site of the enzyme. Mutation of the N-terminal active site of ACE was without effect. Together, our data suggest that ACE inhibitors can initiate the ACE signaling pathway by inducing ACE dimerization, most probably via the C-terminal active site of the enzyme.

  8. No contribution of angiotensin-converting enzyme (ACE) gene variants to severe obesity: a model for comprehensive case/control and quantitative cladistic analysis of ACE in human diseases.

    PubMed

    Bell, Christopher G; Meyre, David; Petretto, Enrico; Levy-Marchal, Claire; Hercberg, Serge; Charles, Marie Aline; Boyle, Cliona; Weill, Jacques; Tauber, Maïte; Mein, Charles A; Aitman, Timothy J; Froguel, Philippe; Walley, Andrew J

    2007-03-01

    Candidate gene analyses are often inconclusive owing to genetic or phenotypic heterogeneity, low statistical power, selection of nonfunctional SNPs, and inadequate statistical analysis of the genetic architecture. Angiotensin-converting enzyme (ACE) is involved in adipocyte growth and function and the ACE-processed angiotensin II inhibits adipocyte differentiation. Associations between body mass index (BMI) and ACE polymorphisms have been reported in general populations, but the contribution to severe obesity of this gene, which is located under an obesity genome-scan linkage peak on 17q23, is unknown. ACE is one of the most studied genes and markers responsible for variation in circulating ACE enzyme levels have been extensively characterised. Eight of these variants were genotyped in 1054 severely obese cases and 918 nonobese controls, as well as 116 nuclear families from the genome scan (n=447), enabling the known clades to be inferred. Qualitative analysis of individual single-nucleotide polymorphisms (SNPs), haplotypes, clades, and diploclades demonstrated no significant associations (P<0.05) after minimal correction for multiple testing. Quantitative analysis of clades and diploclades for BMI, waist-to-hip ratio, or ZBMI in children were also not significant. This rigorous, large-scale study of common, well-defined, severe polygenic obesity provides strong evidence that functionally relevant sequence variation in ACE, whether it is defined at the level of SNPs, haplotypes, or clades, is not associated with severe obesity in French Caucasians. Such a study design exemplifies the strategy needed to clearly define the contribution of the ACE gene to the plethora of complex genetic diseases where weak associations have been previously reported.

  9. Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD)

    PubMed Central

    Ramanathan, Gnanasambandan; Ghosh, Santu; Elumalai, Ramprasad; Periyasamy, Soundararajan; Lakkakula, Bhaskar V.K.S.

    2016-01-01

    Background & objectives: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. Methods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. Results: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. Interpretation & conclusions: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients. PMID:27748299

  10. Angiotensinogen (AGT) M235T, AGT T174M and Angiotensin-1-Converting Enzyme (ACE) I/D Gene Polymorphisms in Essential Hypertension: Effects on Ramipril Efficacy.

    PubMed

    Kolovou, Vana; Lagou, Evangelia; Mihas, Constantinos; Vasiliki, Giannakopoulou; Katsiki, Niki; Kollia, Aikaterini; Triposkiadis, Filippos; Degiannis, Dimitris; Mavrogeni, Sophie; Kolovou, Genovefa

    2015-01-01

    Hypertension, one of the most important risk factors for premature cardiovascular disease, is a major worldwide public health problem. Angiotensin-1-converting enzyme (ACE) and angiotensinogen (AGT) gene polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these gene polymorphisms in an adult population with and without essential hypertension. Furthermore, we evaluated the effect of ACE and AGT gene polymorphisms on ramipril treatment efficacy in the hypertensive patients. A total of 166 adults (83 hypertensives and 83 normotensives) were involved in the study and genotyped for AGTM235T (rs699), AGTT174M (rs4762) and ACEI/D (rs1799752) gene polymorphisms. The genotype and allele distribution of the AGTM235T variant significantly differed between hypertensives and normotensives [odds ratio (OR) = 1.57% (T vs M allele), 95% confidence intervals (CIs): 1.01 - 2.44; p=0.045 for hypertensives]. However, none of the 3 studied Simple Nucleotide Polymorphisms were associated with the blood pressure-lowering response to ramipril. These results suggest that AGTM235T gene polymorphism is associated with essential hypertension. However, none of the AGTM235T, AGTT174M and ACEI/D gene polymorphisms influenced ramipril effectiveness.

  11. [ACE gene polymorphisms associated with serum ACE activity in the Henan Hans of China].

    PubMed

    Kong, Xiang-Dong; Zhang, Si-Zhong

    2004-11-01

    In order to investigate the relationship between gene polymorphisms and serum activity of the angiotensin-1 converting enzyme(ACE) in Chinese population, eight loci in ACE gene were detected by polymerase chain reaction combined with restriction fragment length polymorphism or electrophoresis directly, and serum ACE activity was measured by spectrophometry. Using maximum likelihood estimation(MLE), the pattern of intragenic linkage disequilibrium and the haplotype structure were estimated. All the eight polymorphisms formed nine haplotypes,in which the two most frequent haplotypes were A (A-T-A-T-G-I-A-3) and B(C-C-T-C-A-D-G-2). Also haplotype A and haplotype B were completely different at all eight sites. Deduced from the maximum-parsimony tree,the haplotypes in Chinese population could be grouped into three clades. Clade III seemed to be generated by an ancestral recombination event between clade I and clade II. Every locus formed, the haplotype B was associated with high ACE activity. This findings suggested that serum ACE levels were partially determined by genetic predisposition (the polymorphism of ACE gene). Haplotype B may be related to the quantitative trait loci of high-level activity,whereas high-resolution genetic mapping linked with ACE was still necessary to characterize definitely the functional variants.

  12. Rediscovering ACE: Novel insights into the many roles of the angiotensin-converting enzyme

    PubMed Central

    Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Bernstein, Ellen A.; Janjulia, Tea; Taylor, Brian; Giani, Jorge F.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Shi, Peng D.; Fuchs, Sebastien; Bernstein, Kenneth E.

    2013-01-01

    Angiotensin converting enzyme (ACE) is best known for the catalytic conversion of angiotensin I to angiotensin II. However, the use of gene-targeting techniques has led to mouse models highlighting many other biochemical properties and actions of this enzyme. This review discusses recent studies examining the functional significance of ACE tissue-specific expression and the presence in ACE of two independent catalytic sites with distinct substrates and biological effects. It is these features which explain why ACE makes important contributions to many different physiological processes including renal development, blood pressure control, inflammation and immunity. PMID:23686164

  13. Associations of ACE Gene Insertion/Deletion Polymorphism, ACE Activity, and ACE mRNA Expression with Hypertension in a Chinese Population

    PubMed Central

    He, Qingfang; Fan, Chunhong; Yu, Min; Wallar, Gina; Zhang, Zuo-Feng; Wang, Lixin; Zhang, Xinwei; Hu, Ruying

    2013-01-01

    Background The present study was designed to explore the association of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D, rs4646994) polymorphism, plasma ACE activity, and circulating ACE mRNA expression with essential hypertension (EH) in a Chinese population. In addition, a new detection method for circulating ACE mRNA expression was explored. Methods The research was approved by the ethics committee of Zhejiang Provincial Center for Disease Prevention and Control. Written informed consent was obtained prior to the investigation. 221 hypertensives (cases) and 221 normotensives (controls) were interviewed, subjected to a physical examination, and provided blood for biochemical and genetic tests. The ACE mRNA expression was analyzed by real time fluorescent quantitative Reverse Transcription PCR (FQ-RT-PCR). We performed logistic regression to assess associations of ACE I/D genotypes, ACE activity, and ACE mRNA expression levels with hypertension. Results The results of the multivariate logistic regression analysis showed that the additive model (ID, DD versus II) of the ACE genotype revealed an association with hypertension with adjusted OR of 1.43(95% CI: 1.04-1.97), and ACE ID genotype with adjusted OR of 1.72(95% CI: 1.01-2.92), DD genotype with adjusted OR of 1.94(95% CI: 1.01-3.73), respectively. In addition, our data also indicate that plasma ACE activity (adjusted OR was 1.13(95% CI: 1.08-1.18)) was significantly related to hypertension. However, the plasma ACE mRNA expressions were not different between the cases and controls. Conclusion ACE I/D polymorphism and ACE activity revealed significant influence on hypertension, while circulating ACE mRNA expression was not important factors associated with hypertension in this Chinese population. The detection of circulating ACE mRNA expression by FQ-RT-PCR might be a useful method for early screening and monitoring of EH. PMID:24098401

  14. Human ACE gene polymorphism and distilled water induced cough

    PubMed Central

    Morice, A. H.; Turley, A. J.; Linton, T. K.

    1997-01-01

    BACKGROUND: Inhibitors of angiotensin converting enzyme (ACE) cause a non-productive cough. The insertion/deletion polymorphism of ACE was used as a genetic marker to investigate the relationship between ACE genotype and cough sensitivity. METHODS: A double blind cough challenge was performed in 66 normotensive subjects (34 men) of mean age 34.8 years (range 18-80) using aerosols of distilled water. The number of coughs during the one minute exposure to water was recorded. DNA samples from venous blood were amplified by the polymerase chain reaction and resolved on a 1% agarose gel. They were analysed for the presence of a polymorphism in intron 16 of the ACE gene consisting of an insertion (I) or deletion (D) of an Alu repetitive sequence 287 base pairs long. RESULTS: The distribution of genotypes was 20 II, 26 ID, and 20 DD. The cough response was significantly (p < 0.01) related to the ACE genotype, the mean number of coughs being 15.8, 11.3, and 9.6, respectively, in subjects with the II, ID, and DD genotypes. CONCLUSIONS: The observation that cough challenge is dependent on ACE genotype in normal subjects is evidence of a link between ACE activity and the cough reflex. 


 PMID:9059468

  15. Angiotensin-converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AT1R) gene polymorphisms in generalized aggressive periodontitis.

    PubMed

    Gürkan, Ali; Emingil, Gülnur; Saygan, Buket Han; Atilla, Gül; Köse, Timur; Baylas, Haluk; Berdeli, Afig

    2009-04-01

    Host response to periodontopathic microorganisms can be modulated by genetic factors. Accumulated evidence highlighted the role of renin-angiotensin system (RAS) in inflammatory response thus potential implication of this molecular system in the pathogenesis of periodontitis can be suggested. The present study investigated common genetic variants of molecules within the RAS family namely angiotensin-converting enzyme (ACE), angiotensinogen (AGT) and angiotensin II type 1 receptor (AT1R) in relation to generalized aggressive periodontitis (G-AgP). DNA was obtained from peripheral blood of 103 G-AgP patients and 100 periodontally healthy subjects. ACE I/D, AGT M235T and AT1R A1166C polymorphisms were genotyped by polymerase chain reaction and restriction fragment length polymorphism method. Chi-square, ANOVA and logistic regression were used in statistical analyses. Both ACE I/D and AT1R polymorphisms were similar in G-AgP and healthy groups (p>0.05). G-AgP subjects exhibited decreased AGT TT genotype and T allele frequency as compared to healthy subjects (p<0.05). The same trend was also observed in the nonsmoker subgroup regarding investigated RAS polymorphisms. Present findings suggest that AGT M235T TT genotype and T allele might be associated with decreased risk for G-AgP in Turkish population.

  16. Effect of angiotensin-converting enzyme (ACE) gene polymorphism on progression of renal disease and the influence of ACE inhibition in IDDM patients: findings from the EUCLID Randomized Controlled Trial. EURODIAB Controlled Trial of Lisinopril in IDDM.

    PubMed

    Penno, G; Chaturvedi, N; Talmud, P J; Cotroneo, P; Manto, A; Nannipieri, M; Luong, L A; Fuller, J H

    1998-09-01

    We examined whether the ACE gene insertion/deletion (I/D) polymorphism modulates renal disease progression in IDDM and how ACE inhibitors influence this relationship. The EURODIAB Controlled Trial of Lisinopril in IDDM is a multicenter randomized placebo-controlled trial in 530 nonhypertensive, mainly normoalbuminuric IDDM patients aged 20-59 years. Albumin excretion rate (AER) was measured every 6 months for 2 years. Genotype distribution was 15% II, 58% ID, and 27% DD. Between genotypes, there were no differences in baseline characteristics or in changes in blood pressure and glycemic control throughout the trial. There was a significant interaction between the II and DD genotype groups and treatment on change in AER (P = 0.05). Patients with the II genotype showed the fastest rate of AER progression on placebo but had an enhanced response to lisinopril. AER at 2 years (adjusted for baseline AER) was 51.3% lower on lisinopril than placebo in the II genotype patients (95% CI, 15.7 to 71.8; P = 0.01), 14.8% in the ID group (-7.8 to 32.7; P = 0.2), and 7.7% in the DD group (-36.6 to 37.6; P = 0.7). Absolute differences in AER between placebo and lisinopril at 2 years were 8.1, 1.7, and 0.8 microg/min in the II, ID, and DD groups, respectively. The significant beneficial effect of lisinopril on AER in the II group persisted when adjusted for center, blood pressure, and glycemic control, and also for diastolic blood pressure at 1 month into the study. Progression from normoalbuminuria to microalbuminuria (lisinopril versus placebo) was 0.27 (0.03-2.26; P = 0.2) in the II group, and 1.30 (0.33-5.17; P = 0.7) in the DD group (P = 0.6 for interaction). Knowledge of ACE genotype may be of value in determining the likely impact of ACE inhibitor treatment.

  17. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span.

    PubMed

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-02-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabditis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  18. Interaction of angiotensin-converting enzyme (ACE) with membrane-bound carboxypeptidase M (CPM) - a new function of ACE.

    PubMed

    Sun, Xiaoou; Wiesner, Burkhard; Lorenz, Dorothea; Papsdorf, Gisela; Pankow, Kristin; Wang, Po; Dietrich, Nils; Siems, Wolf-Eberhard; Maul, Björn

    2008-12-01

    Angiotensin-converting enzyme (ACE) demonstrates, besides its typical dipeptidyl-carboxypeptidase activity, several unusual functions. Here, we demonstrate with molecular, biochemical, and cellular techniques that the somatic wild-type murine ACE (mACE), stably transfected in Chinese Hamster Ovary (CHO) or Madin-Darby Canine Kidney (MDCK) cells, interacts with endogenous membranal co-localized carboxypeptidase M (CPM). CPM belongs to the group of glycosylphosphatidylinositol (GPI)-anchored proteins. Here we report that ACE, completely independent of its known dipeptidase activities, has GPI-targeted properties. Our results indicate that the spatial proximity between mACE and the endogenous CPM enables an ACE-evoked release of CPM. These results are discussed with respect to the recently proposed GPI-ase activity and function of sperm-bound ACE.

  19. Angiotensin-converting enzyme (ACE) inhibitors modulate cellular retinol-binding protein 1 and adiponectin expression in adipocytes via the ACE-dependent signaling cascade.

    PubMed

    Kohlstedt, Karin; Gershome, Cynthia; Trouvain, Caroline; Hofmann, Wolf-Karsten; Fichtlscherer, Stephan; Fleming, Ingrid

    2009-03-01

    Inhibitors of the angiotensin-converting enzyme (ACE) decrease angiotensin II production and activate an intracellular signaling cascade that affects gene expression in endothelial cells. Because ACE inhibitors have been reported to delay the onset of type 2 diabetes, we determined ACE signaling-modulated gene expression in endothelial cells and adipocytes. Using differential gene expression analysis, several genes were identified that were 3-fold up- or down-regulated by ramiprilat in cells expressing wild-type ACE versus cells expressing a signaling-dead ACE mutant. One up-regulated gene was the cellular retinol-binding protein 1 (CRBP1). In adipocytes, the overexpression of CRBP1 enhanced (4- to 5-fold) the activity of promoters containing response elements for retinol-dependent nuclear receptors [retinoic acid receptor (RAR) and retinoid X receptor (RXR)] or peroxisome proliferator-activated receptors (PPAR). CRBP1 overexpression also enhanced the promoter activity (by 470 +/- 40%) and expression/release of the anti-inflammatory and antiatherogenic adipokine adiponectin (cellular adiponectin by 196 +/- 24%, soluble adiponectin by 228 +/- 74%). Significantly increased adiponectin secretion was also observed after ACE inhibitor treatment of human preadipocytes, an effect prevented by small interfering RNA against CRBP1. Furthermore, in ob/ob mice, ramipril markedly potentiated both the basal (approximately 2-fold) and rosiglitazonestimulated circulating levels of adiponectin. In patients with coronary artery disease or type 2 diabetes, ACE inhibition also significantly increased plasma adiponectin levels (1.6- or 2.1-fold, respectively). In summary, ACE inhibitors affect adipocyte homeostasis via CRBP1 through the activation of RAR/RXR-PPAR signaling and up-regulation of adiponectin. The latter may contribute to the beneficial effects of ACE inhibitors on the development of type 2 diabetes in patients with an activated renin-angiotensin system.

  20. Angiotensin Converting Enzyme (ACE) Inhibitor Extends Caenorhabditis elegans Life Span

    PubMed Central

    Kumar, Sandeep; Dietrich, Nicholas; Kornfeld, Kerry

    2016-01-01

    Animal aging is characterized by progressive, degenerative changes in many organ systems. Because age-related degeneration is a major contributor to disability and death in humans, treatments that delay age-related degeneration are desirable. However, no drugs that delay normal human aging are currently available. To identify drugs that delay age-related degeneration, we used the powerful Caenorhabdtitis elegans model system to screen for FDA-approved drugs that can extend the adult lifespan of worms. Here we show that captopril extended mean lifespan. Captopril is an angiotensin-converting enzyme (ACE) inhibitor used to treat high blood pressure in humans. To explore the mechanism of captopril, we analyzed the acn-1 gene that encodes the C. elegans homolog of ACE. Reducing the activity of acn-1 extended the mean life span. Furthermore, reducing the activity of acn-1 delayed age-related degenerative changes and increased stress resistance, indicating that acn-1 influences aging. Captopril could not further extend the lifespan of animals with reduced acn-1, suggesting they function in the same pathway; we propose that captopril inhibits acn-1 to extend lifespan. To define the relationship with previously characterized longevity pathways, we analyzed mutant animals. The lifespan extension caused by reducing the activity of acn-1 was additive with caloric restriction and mitochondrial insufficiency, and did not require sir-2.1, hsf-1 or rict-1, suggesting that acn-1 functions by a distinct mechanism. The interactions with the insulin/IGF-1 pathway were complex, since the lifespan extensions caused by captopril and reducing acn-1 activity were additive with daf-2 and age-1 but required daf-16. Captopril treatment and reducing acn-1 activity caused similar effects in a wide range of genetic backgrounds, consistent with the model that they act by the same mechanism. These results identify a new drug and a new gene that can extend the lifespan of worms and suggest new

  1. The Pneumocystis Ace2 transcription factor regulates cell wall-remodeling genes and organism virulence.

    PubMed

    Kottom, Theodore J; Limper, Andrew H

    2013-08-16

    Pneumocystis carinii (Pc) β-glucans are major components of the organism cell wall; yet, the regulation of Pc cell wall genesis and remodeling is not well understood. Ace2 transcription factors, which are present in many fungi, regulate glucanases and other enzymes needed for cell wall remodeling. The cloning and heterologous expression of PcAce2 in ace2Δ Saccharomyces cerevisiae demonstrated that PcAce2 can restore the defective glucanase and endochitinase gene expression of the mutant as well as regulate cell wall β-glucan biosynthetic genes. Furthermore, when a reconstructed yeast system was used, PcAce2 activated the transcription of the Pneumocystis gsc1 β-glucan synthetase, confirming the activity of a Pc transcription factor on a native Pneumocystis promoter and gene for the first time. We further observed that Pneumocystis binding to host extracellular matrix proteins and lung epithelial cells induced the phosphorylation (activation) of the PcAce2 transcription factor. Finally, we present a novel method that confirms the role of PcAce2 in modulating organism virulence using ace2Δ Candida glabrata infection in neutropenic mice. Together, these results indicate that the adherence of Pc to lung matrix proteins and epithelial cells leads to the activation of the Ace2 transcription factor, which regulates cell wall degradation and biosynthesis genes that are required for cell wall remodeling.

  2. ACE

    NASA Technical Reports Server (NTRS)

    Lumia, R.

    1999-01-01

    This document describes the progress made during the fourth year of the Center for Autonomous Control Engineering (ACE). We currently support 30 graduate students, 52 undergraduate students, 9 faculty members, and 4 staff members. Progress will be divided into two categories. The first category explores progress for ACE in general. The second describes the results of each specific project supported within ACE.

  3. ACE

    NASA Technical Reports Server (NTRS)

    Lumia, R.

    1999-01-01

    This document describes the progress made during the fourth year of the Center for Autonomous Control Engineering (ACE). We currently support 30 graduate students, 52 undergraduate students, 9 faculty members, and 4 staff members. Progress will be divided into two categories. The first category explores progress for ACE in general. The second describes the results of each specific project supported within ACE.

  4. Rapid methods for population-scale analysis for gene polymorphisms: the ACE gene as an example.

    PubMed Central

    O'Dell, S. D.; Humphries, S. E.; Day, I. N.

    1995-01-01

    OBJECTIVE--To obtain rapid, high throughput genotyping of the angiotensin converting enzyme (ACE) gene intron 16 insertion/deletion polymorphism. METHODS--DNA was obtained from whole blood samples by a simple liquid phase methanol extraction procedure. The ACE gene was amplified by the polymerase chain reaction (PCR) using two oligonucleotide primers (ACE1 and ACE3) outside the insertion sequence and one primer (ACE2) inside the sequence. Microtitre array diagonal gel electrophoresis (MADGE) was used to determine genotypes. RESULTS--84 and 65 bp PCR products indicating the presence of deletion (D) and insertion (I) alleles, respectively, were clearly resolved after electrophoresis on a 7.5% polyacrylamide gel. Up to 480 DNA samples on 5 gels could be genotyped in a single electrophoresis run, or up to 1000 samples in a working day. CONCLUSIONS--A simplified DNA extraction protocol coupled to the high throughput capability of the MADGE electrophoretic system for genotyping enables analysis of large populations for association studies of ACE genotype with cardiac disease events. Images PMID:7756072

  5. Characterization of angiotensin converting enzyme (ACE) in the testis and assessment of the in vivo effects of the ACE inhibitor perindopril

    SciTech Connect

    Jackson, B.; Cubela, R.B.; Sakaguchi, K.; Johnston, C.I.

    1988-07-01

    Angiotensin converting enzyme (ACE) was characterized by radioligand studies utilizing the potent ACE inhibitor 351A, a derivative of lisinopril. Ligand binding characteristics were similar for ACE derived from testis, lung, and kidney, despite known differences in structure between ACe from these sources. This observation suggests that the ACE active enzymatic site is similar in different tissues. The effect of the orally active ACE inhibitor perindopril was studied ex vivo in tissues of the rat after oral gavage. Radioligand bound to tissue ACE was reduced after perindopril treatment, in tissue homogenates of lung and kidney, but not testis. Autoradiographs of radioligand binding to tissue sections obtained ex vivo after oral perindopril showed inhibition of ACE in the aorta, lung, and kidney, but did not reveal any inhibition of ACE in the testis. ACE in small vessels of the testis was inhibited as in the aorta, while at the same time testicular ACE was unaffected. ACE in rat testis appears to have a similar enzymatic binding site to ACE from the lung and kidney. Perindopril inhibited ACE in the lung and kidney but did not affect ACE in the testis, suggesting the drug is limited in testicular penetration by the blood-testis barrier. This may explain the lack of any reports of adverse effects of ACE inhibitors on testicular function.

  6. Calmodulin interacts with angiotensin-converting enzyme-2 (ACE2) and inhibits shedding of its ectodomain.

    PubMed

    Lambert, Daniel W; Clarke, Nicola E; Hooper, Nigel M; Turner, Anthony J

    2008-01-23

    Angiotensin-converting enzyme-2 (ACE2) is a regulatory protein of the renin-angiotensin system (RAS) and a receptor for the causative agent of severe-acute respiratory syndrome (SARS), the SARS-coronavirus. We have previously shown that ACE2 can be shed from the cell surface in response to phorbol esters by a process involving TNF-alpha converting enzyme (TACE; ADAM17). In this study, we demonstrate that inhibitors of calmodulin also stimulate shedding of the ACE2 ectodomain, a process at least partially mediated by a metalloproteinase. We also show that calmodulin associates with ACE2 and that this interaction is decreased by calmodulin inhibitors.

  7. Angiotensin I-Converting Enzyme (ACE) Inhibitory Activity and ACE Inhibitory Peptides of Salmon (Salmo salar) Protein Hydrolysates Obtained by Human and Porcine Gastrointestinal Enzymes

    PubMed Central

    Darewicz, Małgorzata; Borawska, Justyna; Vegarud, Gerd E.; Minkiewicz, Piotr; Iwaniak, Anna

    2014-01-01

    The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes. PMID:25123137

  8. Angiotensin I-converting enzyme (ACE) inhibitory activity and ACE inhibitory peptides of salmon (Salmo salar) protein hydrolysates obtained by human and porcine gastrointestinal enzymes.

    PubMed

    Darewicz, Małgorzata; Borawska, Justyna; Vegarud, Gerd E; Minkiewicz, Piotr; Iwaniak, Anna

    2014-08-13

    The objectives of the present study were two-fold: first, to detect whether salmon protein fractions possess angiotensin I-converting enzyme (ACE) inhibitory properties and whether salmon proteins can release ACE inhibitory peptides during a sequential in vitro hydrolysis (with commercial porcine enzymes) and ex vivo digestion (with human gastrointestinal enzymes). Secondly, to evaluate the ACE inhibitory activity of generated hydrolysates. A two-step ex vivo and in vitro model digestion was performed to simulate the human digestion process. Salmon proteins were degraded more efficiently by porcine enzymes than by human gastrointestinal juices and sarcoplasmic proteins were digested/hydrolyzed more easily than myofibrillar proteins. The ex vivo digested myofibrillar and sarcoplasmic duodenal samples showed IC50 values (concentration required to decrease the ACE activity by 50%) of 1.06 and 2.16 mg/mL, respectively. The in vitro hydrolyzed myofibrillar and sarcoplasmic samples showed IC50 values of 0.91 and 1.04 mg/mL, respectively. Based on the results of in silico studies, it was possible to identify 9 peptides of the ex vivo hydrolysates and 7 peptides of the in vitro hydrolysates of salmon proteins of 11 selected peptides. In both types of salmon hydrolysates, ACE-inhibitory peptides IW, IY, TVY and VW were identified. In the in vitro salmon protein hydrolysates an ACE-inhibitory peptides VPW and VY were also detected, while ACE-inhibitory peptides ALPHA, IVY and IWHHT were identified in the hydrolysates generated with ex vivo digestion. In our studies, we documented ACE inhibitory in vitro effects of salmon protein hydrolysates obtained by human and as well as porcine gastrointestinal enzymes.

  9. Polymorphism of the angiotensin-converting enzyme (ACE) and angiotesinogen (AGT) genes and their associations with blood pressure and carotid artery intima media thickness among healthy Finnish young adults--the Cardiovascular Risk in Young Finns Study.

    PubMed

    Islam, Md Shaheenul; Lehtimäki, Terho; Juonala, Markus; Kähönen, Mika; Hutri-Kähönen, Nina; Kainulainen, Katariina; Miettinen, Helena; Taittonen, Leena; Kontula, Kimmo; Viikari, Jorma S A; Raitakari, Olli T

    2006-10-01

    The roles of angiotensin converting enzyme (ACE) insertion-deletion (I/D) and angiotensinogen (AGT) m235t polymorphisms in cardiovascular diseases have been investigated extensively during the past decade but results have been inconsistent. A sex-specific association between the ACE I/D polymorphism and systolic blood pressure (BP) was seen among Finnish children and adolescents previously. We investigated if these polymorphisms associate with the BP and carotid artery intima media thickness (IMT) in the same cohort during their adulthood. IMT data were available for 224 ACE I/D genotyped individuals and 202 AGT m235t genotyped individuals. Systolic and diastolic blood pressure values did not differ between ACE and AGT genotypes. Age and BMI adjusted mean IMT was 0.02 (95% CI: -0.05 to 0.02, p=0.33) and 0.03 mm (95% CI: -0.07 to 0.001, p=0.06) lower among the ID and DD genotype groups, respectively, compared to the II genotype group. MT and TT genotype groups had 0.02 mm (95% CI: -0.01 to 0.05, p=0.17) higher and 0.01 mm (95% CI: -0.04 to 0.02, p=0.59) lower mean IMT, respectively, compared to the MM genotype group. We conclude that ACE I/D and AGT m235t polymorphisms are not associated with carotid IMT in healthy young Finnish adults.

  10. ACE gene titration in mice uncovers a new mechanism for ACE on the control of body weight.

    PubMed

    Heimann, A S; Favarato, M H; Gozzo, F C; Rioli, V; Carreño, F R; Eberlin, M N; Ferro, E S; Krege, J H; Krieger, J E

    2005-01-20

    Mice harboring 1, 2, or 3 copies of the angiotensin-converting enzyme (ACE) gene were used to evaluate the quantitative role of the ACE locus on obesity. Three-copy mice fed with a high-fat diet had lower body weight and peri-epididymal adipose tissue than did 1- and 2-copy mice (P < 0.05). On regular diet, 3-copy mice had to eat more to maintain the same body weight; on a high-fat diet, they ate the same but weighed less than 1- and 2-copy mice (P < 0.05), indicating a higher metabolic rate in 3-copy mice that was not affected by ANG II AT(1) blocker treatment. A catalytically inactive form of thimet oligopeptidase (EC 3.4.24.15; EP24.15) was used to isolate ACE substrates from adipose tissue. Liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) identified 162 peptide peaks; 16 peptides were present in both groups (1- and 3-copy mice fed with a high-fat diet), whereas 58 of the 72 unique peptides were found only in the 3-copy mice. Peptide size distribution was shifted to lower molecular weight in 3-copy mice. Two of the identified peptides, LVVYPWTQRY and VVYPWTQRY, which are ACE substrates, inhibited in vitro protein kinase C phosphorylation in a concentration-dependent manner. In addition, neurolysin (EC 3.4.24.16; EP24.16) activity was lower in fat tissue from 3- vs. 1-copy mice (P < 0.05). Taken together, these results provide evidence that ACE is associated with body weight and peri-epididymal fat accumulation. This response may involve the generation of oligopeptides that inhibit the activity of EP24.16 and other oligopeptidases within the adipose tissue.

  11. Multilocus analysis in candidate genes ACE, AGT, and AGTR1 and predisposition to peripheral arterial disease: role of ACE D/-240T haplotype.

    PubMed

    Fatini, Cinzia; Sticchi, Elena; Sofi, Francesco; Said, Abdihakim Abdullahi; Pratesi, Giovanni; Pulli, Raffaele; Pratesi, Carlo; Abbate, Rosanna

    2009-12-01

    Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis. Apart from traditional cardiovascular risk factors, several novel biologic mediators and genetic predisposing factors appear relevant in determining the atherogenetic process leading to PAD. Genes encoding for renin angiotensin system (RAS) components have been proposed as candidate in atherosclerosis. This study investigated four polymorphisms in angiotensinogen (AGT), angiotensin converting enzyme (ACE), and angiotensin II receptor type 1 (AGTR1), genes of RAS, in both predicting PAD and modulating the severity of the disease. The ACE I/D and -240A>T, AGT M235T, and AGTR1 1166A>C polymorphisms were analyzed in 281 PAD patients and in 485 controls comparable for age and sex. The ACE D and -240T alleles both significantly influenced the predisposition to PAD. The ACE D, but not -240 T, allele remained associated with PAD after Bonferroni correction (P = .004) and adjustment for cardiovascular risk factors (P = .03). The ACE D allele influenced PAD predisposition with a dose-dependent effect (odds ratio for ACE ID vs II genotype, 1.77; P = .006; ACE DD vs II genotype, 2.15; P = .001). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T haplotype significantly and independently influenced the predisposition to PAD (P = .02). In 190 PAD patients with no additional atherosclerotic localizations (isolated PAD), a significant association between ACE D and -240T alleles and PAD was observed. Only the ACE D allele remained associated with isolated PAD after Bonferroni correction (P = .02) and after adjustment for cardiovascular risk factors (P = .02). The haplotype reconstruction analysis for the ACE gene showed that the D/-240T, but not the D/-240A haplotype significantly influenced the predisposition to PAD (P = .0003). No influence of the polymorphisms analyzed on the severity of the disease, according to Rutherford categories, was found. The present study

  12. Angiotensin-I-Converting Enzyme (ACE)-Inhibitory Peptides from Plants

    PubMed Central

    Daskaya-Dikmen, Ceren; Yucetepe, Aysun; Karbancioglu-Guler, Funda; Daskaya, Hayrettin; Ozcelik, Beraat

    2017-01-01

    Hypertension is an important factor in cardiovascular diseases. Angiotensin-I-converting enzyme (ACE) inhibitors like synthetic drugs are widely used to control hypertension. ACE-inhibitory peptides from food origins could be a good alternative to synthetic drugs. A number of plant-based peptides have been investigated for their potential ACE inhibitor activities by using in vitro and in vivo assays. These plant-based peptides can be obtained by solvent extraction, enzymatic hydrolysis with or without novel food processing methods, and fermentation. ACE-inhibitory activities of peptides can be affected by their structural characteristics such as chain length, composition and sequence. ACE-inhibitory peptides should have gastrointestinal stability and reach the cardiovascular system to show their bioactivity. This paper reviews the current literature on plant-derived ACE-inhibitory peptides including their sources, production and structure, as well as their activity by in vitro and in vivo studies and their bioavailability. PMID:28333109

  13. Null association between ACE gene I/D polymorphism and diabetic nephropathy among multiethnic Malaysian subjects.

    PubMed

    Jayapalan, Jaime J; Muniandy, Sekaran; Chan, Siew P

    2010-05-01

    Wide inter-ethnic allelic variations of the Angiotensin Converting Enzyme (ACE) i nsertion-deletion (I/D) gene polymorphism were thought to be responsible for the conflicting gene-diabetic nephropathy disease association worldwide. We have investigated the genetic susceptibility of the ACE gene to diabetic nephropathy in the multiethnic Malaysian population. A total of 137 healthy (control) and 256 diabetic subjects were recruited. The diabetic subjects were further subdivided according to their nephropathy status based on urinary albumin-creatinine ratio (ACR) and glomerular filtration rate (GFR). Triple primer polymerase chain reaction (PCR) was used for ACE I/D genotyping. Subsequently, populationwide genetic analysis and gene-disease association studies were performed. The genotype frequencies in all subgroups were in Hardy-Weinberg equilibrium. Similar allelic and genotypic frequency of ACE I/D gene polymorphism was observed between healthy controls versus pooled type 2 diabetes mellitus (T2DM) subjects, and normoalbuminuria versus microalbuminuria, macroalbuminuria and End Stage Renal Failure (ESRF) (P > 0.05). Neither ethnicity nor gender exerted any influence on the ACE I/D gene polymorphism (P > 0.05), with the exception of the Chinese ethnic group which exhibited a higher frequency of ID genotype (P = 0.042). A multinomial logistic regression model showed that predictive factors including age, systolic blood pressure (SBP), high density lipoprotein (HDL) and glycosylated hemoglobin (HbA1C) were independently associated with diabetic nephropathy, in that order. The I/D polymorphism of the ACE gene is not significantly associated with both T2DM and/or diabetic nephropathy in this Malaysian population regardless of ethnicity and gender.

  14. Variation in the ACE, PPARGC1A and PPARA genes in Lithuanian football players.

    PubMed

    Gineviciene, Valentina; Jakaitiene, Audrone; Tubelis, Linas; Kucinskas, Vaidutis

    2014-01-01

    The aim of this study was to determine the impact of ACE (I/D), PPARGC1A (G/A) and PPARA (G/C) polymorphisms on footballers performance among 199 Lithuanian professional footballers and 167 sedentary, healthy men (controls). Genotyping was performed using polymerase chain reaction and restriction fragment length polymorphism methods on DNA from leucocytes. Results revealed that the angiotensin-1-coverting enzyme gene (ACE) genotype distribution was significantly different between total football players group (II 23.6%, ID 46.7% and DD 29.6%) and the controls (II 24.6%, ID 29.9% and DD 45.5%; P=0.002). Although investigating PPARGC1A (G/A) and PPARA (G/C) polymorphisms no significant results were obtained in the total football players group, however, significant differences were determined between forwards and controls [PPARGC1A: GG 54.6%, GA 29.5%, AA 15.9% vs. GG 49.7%, GA 44.3% and AA 6.0% (P = 0.044); PPARA: GG 52.3%, GC 40.9%, CC 6.8% vs. GG 72.4%, GC 24.6% and CC 3.0% (P = 0.034)]. In the whole cohort, the odds ratio of the genotype [ACE ID + PPARA GG] being a footballer was 1.69 (95% CI 1.04-2.74), and of [ACE ID + PPARGC1A GG] 1.93 (95% CI 1.10-3.37) and of [ACE II + PPARA GC] 2.83 (95% CI 1.02-7.91) compared to controls. It was revealed that ACE ID genotype together with PPARA GG and PPARGC1A GG as well as ACE II genotype with PPARA GC is probably the 'preferable genotype' for footballers. Summing up, the present study suggests that the ACE, PPARGC1A and PPARA polymorphisms genotypes are associated, separately and in combination, with Lithuanian footballers' performance.

  15. Angiotensin-converting enzyme-2 (ACE2): comparative modeling of the active site, specificity requirements, and chloride dependence.

    PubMed

    Guy, Jodie L; Jackson, Richard M; Acharya, K Ravi; Sturrock, Edward D; Hooper, Nigel M; Turner, Anthony J

    2003-11-18

    Angiotensin-converting enzyme 2 (ACE2), a homologue of ACE, represents a new and potentially important target in cardio-renal disease. A model of the active site of ACE2, based on the crystal structure of testicular ACE, has been developed and indicates that the catalytic mechanism of ACE2 resembles that of ACE. Structural differences exist between the active site of ACE (dipeptidyl carboxypeptidase) and ACE2 (carboxypeptidase) that are responsible for the differences in specificity. The main differences occur in the ligand-binding pockets, particularly at the S2' subsite and in the binding of the peptide carboxy-terminus. The model explains why the classical ACE inhibitor lisinopril is unable to bind to ACE2. On the basis of the ability of ACE2 to cleave a variety of biologically active peptides, a consensus sequence of Pro-X-Pro-hydrophobic/basic for the protease specificity of ACE2 has been defined that is supported by the ACE2 model. The dipeptide, Pro-Phe, completely inhibits ACE2 activity at 180 microM with angiotensin II as the substrate. As with ACE, the chloride dependence of ACE2 is substrate-specific such that the hydrolysis of angiotensin I and the synthetic peptide substrate, Mca-APK(Dnp), are activated in the presence of chloride ions, whereas the cleavage of angiotensin II is inhibited. The ACE2 model is also suggestive of a possible mechanism for chloride activation. The structural insights provided by these analyses for the differences in inhibition pattern and substrate specificity among ACE and its homologue ACE2 and for the chloride dependence of ACE/ACE2 activity are valuable in understanding the function and regulation of ACE2.

  16. Investigation of ACE, ACE2 and AGTR1 genes for association with nephropathy in Type 1 diabetes mellitus.

    PubMed

    Currie, D; McKnight, A J; Patterson, C C; Sadlier, D M; Maxwell, A P

    2010-10-01

    Polymorphisms in ACE and AGTR1 genes have been assessed in multiple studies for association with diabetic nephropathy; however, results are conflicting. The ACE2 gene has not been studied extensively for association with diabetic nephropathy. We investigated variants in ACE, ACE2 and AGTR1 for association with nephropathy in a case-control group (1467 participants with Type1 diabetes, case subjects n=718; control subjects n=749) of white descent with grandparents born in the British Isles. All recruited individuals were carefully phenotyped and genotyping was performed using Sequenom, Taqman and gel electrophoresis methods. The χ(2) -test for contingency tables was used to compare genotype and allele frequencies in case and control groups. No departure from Hardy-Weinberg equilibrium was observed in cases or controls. Two variants within the ACE gene (rs4293, P(allelic) =0.02, P(genotypic) =0.008; rs4309, P(allelic) =0.02, P(genotypic) =0.01) were significantly associated with nephropathy at the 5% level. No variant remained statistically significant following adjustment for multiple comparisons. No single nucleotide polymorphisms in the ACE2 or AGTR1 genes were significantly associated with nephropathy when analysed either by genotype or allele frequencies. Our independent case-control study provides no evidence that common variants in ACE, ACE2 and AGTR1 play a major role in genetic susceptibility to diabetic nephropathy in a white population with Type1 diabetes. © 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.

  17. Angiotensin-I-Converting Enzyme (ACE) Inhibitors from Marine Resources: Prospects in the Pharmaceutical Industry

    PubMed Central

    Wijesekara, Isuru; Kim, Se-Kwon

    2010-01-01

    Hypertension or high blood pressure is one of the major independent risk factors for cardiovascular diseases. Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE) plays an important physiological role in regulation of blood pressure by converting angiotensin I to angiotensin II, a potent vasoconstrictor. Therefore, the inhibition of ACE activity is a major target in the prevention of hypertension. Recently, the search for natural ACE inhibitors as alternatives to synthetic drugs is of great interest to prevent several side effects and a number of novel compounds such as bioactive peptides, chitooligosaccharide derivatives (COS) and phlorotannins have been derived from marine organisms as potential ACE inhibitors. These inhibitory derivatives can be developed as nutraceuticals and pharmaceuticals with potential to prevent hypertension. Hence, the aim of this review is to discuss the marine-derived ACE inhibitors and their future prospects as novel therapeutic drug candidates for treat hypertension. PMID:20479968

  18. Angiotensin-converting enzyme (ACE and ACE2) imbalance correlates with the severity of cerulein-induced acute pancreatitis in mice.

    PubMed

    Liu, Ruixia; Qi, Haiyu; Wang, Jing; Wang, Yan; Cui, Lijian; Wen, Yan; Yin, Chenghong

    2014-04-01

    Angiotensin-converting enzyme (ACE) and its effector peptide angiotensin II (Ang II) have been implicated in the pathogenesis of pancreatitis. Angiotensin-converting enzyme 2 (ACE2) degrades Ang II to angiotensin-(1-7) [Ang-(1-7)] and has recently been described to have an antagonistic effect on ACE signalling. However, the specific underlying role of ACE2 in the pathogenesis of severe acute pancreatitis (SAP) is unclear. In the present study, the local imbalance of ACE and ACE2, as well as Ang II and Ang-(1-7) expression, was compared in wild-type (WT) and ACE2 knock-out (KO) or ACE2 transgenic (TG) mice subjected to cerulein-induced SAP. Serum amylase, tumour necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-10 levels and histological morphometry were used to determine the severity of pancreatitis. In WT mice, pancreatic ACE and Ang II and serum Ang II expression increased (P < 0.05), while pancreatic ACE2 and Ang-(1-7) and serum Ang-(1-7) levels were also significantly elevated (P < 0.05) from 2 to 72 h after the onset of SAP. However, the ratio of pancreatic ACE2 to ACE expression was significantly reduced (from 1.46 ± 0.09 to 0.27 ± 0.05, P < 0.001) and paralleled the severity of pancreatitis. The Ace2 KO mice exhibited increased levels of tumour necrosis factor-α, IL-1β, IL-6, multifocal coagulative necrosis and inflammatory infiltrate, and lower levels of serum IL-10 and pancreatic Ang-(1-7) (4.70 ± 2.13 versus 10.87 ± 2.51, P < 0.001) compared with cerulein-treated WT mice at the same time point. Conversely, Ace2 TG mice with normal ACE expression were more resistant to SAP challenge as evidenced by a decreased inflammatory response, attenuated pathological changes and increased survival rates. These data suggest that the ACE2-ACE imbalance plays an important role in the pathogenesis of SAP and that pancreatic ACE2 is an important factor in determining the severity of SAP.

  19. Docking Studies of Methylthiomorpholin Phenols (LQM300 Series) with Angiotensin-Converting Enzyme (ACE)

    PubMed Central

    Vázquez-Valadez, Víctor H.; Abrego, V.H.; Martínez, Pablo A.; Torres, Gabriela; Zúñiga, Oscar; Escutia, Daniel; Vilchis, Rebeca; Velázquez, Ana Ma.; Martínez, Luisa; Ruiz, Mónica; Camacho, Brígida; López-Castañares, Rafael; Angeles, Enrique

    2013-01-01

    A main target in the treatment of hypertension is the angiotensin-converting enzyme (ACE). This enzyme is responsible for producing angiotensin II, a potent vasoconstrictor. Therefore, one of the targets in the treatment of hypertension is to inhibit ACE activity. Hence, this study’s aim is to use computational studies to demonstrate that the proposed heterocyclic compounds have a molecular affinity for ACE and that, furthermore, these heterocyclic compounds are capable of inhibiting ACE activity, thus avoiding the production of the vasopressor Angiotensin II. All this using computer-aided drug design, and studying the systems, with the proposed compounds, through molecular recognition process and compared with the compounds already on the market for hypertension. PMID:24319502

  20. Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity

    PubMed Central

    Wijesinghe, W.A.J.P.; Ko, Seok-Chun

    2011-01-01

    Inhibition of angiotensin I-converting enzyme (ACE) activity is the most common mechanism underlying the lowering of blood pressure. In the present study, five organic extracts of a marine brown seaweed Ecklonia cava were prepared by using ethanol, ethyl acetate, chloroform, hexane, and diethyl ether as solvents, which were then tested for their potential ACE inhibitory activities. Ethanol extract showed the strongest ACE inhibitory activity with an IC50 value of 0.96 mg/ml. Five kinds of phlorotannins, phloroglucinol, triphlorethol-A, eckol, dieckol, and eckstolonol, were isolated from ethanol extract of E. cava, which exhibited potential ACE inhibition. Dieckol was the most potent ACE inhibitor and was found to be a non-competitive inhibitor against ACE according to Lineweaver-Burk plots. Dieckol had an inducible effect on the production of NO in EAhy926 cells without having cytotoxic effect. The results of this study indicate that E. cava could be a potential source of phlorotannins with ACE inhibitory activity for utilization in production of functional foods. PMID:21556221

  1. Effect of phlorotannins isolated from Ecklonia cava on angiotensin I-converting enzyme (ACE) inhibitory activity.

    PubMed

    Wijesinghe, W A J P; Ko, Seok-Chun; Jeon, You-Jin

    2011-04-01

    Inhibition of angiotensin I-converting enzyme (ACE) activity is the most common mechanism underlying the lowering of blood pressure. In the present study, five organic extracts of a marine brown seaweed Ecklonia cava were prepared by using ethanol, ethyl acetate, chloroform, hexane, and diethyl ether as solvents, which were then tested for their potential ACE inhibitory activities. Ethanol extract showed the strongest ACE inhibitory activity with an IC(50) value of 0.96 mg/ml. Five kinds of phlorotannins, phloroglucinol, triphlorethol-A, eckol, dieckol, and eckstolonol, were isolated from ethanol extract of E. cava, which exhibited potential ACE inhibition. Dieckol was the most potent ACE inhibitor and was found to be a non-competitive inhibitor against ACE according to Lineweaver-Burk plots. Dieckol had an inducible effect on the production of NO in EAhy926 cells without having cytotoxic effect. The results of this study indicate that E. cava could be a potential source of phlorotannins with ACE inhibitory activity for utilization in production of functional foods.

  2. Is the association between ACE genes and blood pressure mediated by postnatal growth during the first 3 years?

    PubMed

    Min, JungWon; Kim, Young Ju; Lee, Hwayoung; Park, Eun Ae; Cho, Su Jin; Hong, Young Mi; Oh, Se-Young; Ha, Eunhee; Kang, DukHee; Park, Hyesook

    2012-06-01

    Unlike the defined role of angiotensin-converting enzyme (ACE) gene in adult hypertension, ACE gene did not show direct influence on childhood blood pressure (BP), rather, seemed to be related to childhood growth with age-dependent characteristics. Thus, we examined intermediate effects of postnatal growth between the ACE polymorphisms and BP. We analyzed data from 257 children born in 2001-04 at Ewha Womans University Hospital in Seoul, Korea, and followed them up until 3 years of age. Children with excessive adiposity had higher BP, as rapid growers did to no-change and decelerated growers. The ACE II genotype was associated with greater growth acceleration than the DD genotype (II: 46.8% vs. DD: 23.9%), and with a higher BP. The interactions between ACE genotype and adiposity at age 3 were significant on the BP levels. The highest BP increase with the same degree of adiposity was observed in those with the II genotype [β (SE) for BMI: 1.9 (0.9), p=0.04]; particularly, only rapid grown II carriers demonstrated statistical significance on this linear association. These results suggested that ACE polymorphisms and BP association are mediated by postnatal growth. Further studies are required to determine the age-specific ACE genetic effects and its undefined biological mechanism. Copyright © 2011 Elsevier Ltd. All rights reserved.

  3. MTHFR gene C677T mutation and ACE gene I/D polymorphism in Turkish patients with osteoarthritis.

    PubMed

    Inanir, Ahmet; Yigit, Serbulent; Tural, Sengul; Cecen, Osman; Yildirim, Eren

    2013-01-01

    Osteoarthritis is a degenerative joint disorder resulting in destruction of articular cartilage, osteophyte formation, and subchondral bone sclerosis. In recent years, numerous genetic factors have been identified and implicated in osteoarthritis. The aim of the current study was to examine the influence of methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) variations on the risk of osteoarthritis. Genomic DNA is obtained from 421 persons (221 patients with osteoarthritis and 200 healthy controls). ACE gene I/D polymorphism genotypes were determined using polymerase chain reaction using I and D allele-specific primers. The MTHFR C677T mutation was analyzed by polymerase chain reaction (PCR) based restriction fragment length polymorphism (RFLP) methods. We found significant difference between the groups with respect to both ACE and MTHFR genotype distributions (p< 0.001, p< 0.001 respectively). Our study suggests that ACE gene DD genotype and MTHFR gene CC genotype could be used as genetic markers in osteoarthritis in Turkish study populations.

  4. Association Between ACE Gene Polymorphism and QT Dispersion in Patients with Acute Myocardial Infarction.

    PubMed

    Karahan, Zulkuf; Ugurlu, Murat; Ucaman, Berzal; Veysel Ulug, Ali; Kaya, Ilyas; Cevik, Kemal; Sahin Adiyaman, Mehmet; Oztürk, Onder; Iyem, Hikmet; Ozdemir, Ferit

    2016-01-01

    Angiotensin converting enzyme (ACE) gene polymorphism is associated with high renin-angiotensin system causing myocardial fibrosis and ventricular repolarization abnormality. Based on these findings, this study was designed to determine the association between ACE gene insertion/deletion (I/D) polymorphism and QT dispersion after acute myocardial infarction (MI). The study included 108 patients with acute MI. Blood samples were obtained from all the patients for genomic DNA analysis. ECGs were recorded at baseline and at the end of a 6-month follow up. The OT dispersion was manually calculated. The mean age of the patients was 57.5 ±9.9 years (ranging from 36 to 70). The patients with DD genotype showed longer QT dispersion than patients with II or DI genotype at the baseline, while at the end of the six-month follow up the patients with DI genotype showed longer QT dispersion than patients with DD or II genotypes. However, the magnitude of the QT dispersion prolongation was higher in patients carrying the ACE D allele than patients who were not carrying it, at baseline and at the end of six-month follow up (52.5 ±2.6 msn vs. 47.5±2.1 msn at baseline, 57±3.2 msn vs. 53±2.6 msn in months, P: 0.428 and P: 0.613, respectively). Carriers of the D allele of ACE gene I/D polymorphism may be associated with QT dispersion prolongation in patients with MI.An interaction of QT dispersion and ACE gene polymorphism may be associated with an elevation of serum type I-C terminal pro-collagen concentration, possibly leading to myocardial fibrosis, and increased action potential duration.

  5. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  6. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  7. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  8. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  9. 21 CFR 862.1090 - Angiotensin converting enzyme (A.C.E.) test system.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Angiotensin converting enzyme (A.C.E.) test system. 862.1090 Section 862.1090 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry...

  10. ACE and ACTN3 genes polymorphisms among female Hungarian athletes in the aspect of sport disciplines.

    PubMed

    Bosnyák, E; Trájer, E; Udvardy, A; Komka, Z; Protzner, A; Kováts, T; Györe, I; Tóth, M; Pucsok, J; Szmodis, M

    2015-12-01

    The aim of the study was to determine the importance of two sport-associated gene polymorphisms, alpha-actinin-3 R577X (ACTN3) and angiotensin-converting enzyme I/D (ACE), among Hungarian athletes in different sports. The examination was carried out only on women (n = 100). Sport-specific groups were formed in order to guarantee the most homogeneous clusters. Human genomic DNA was isolated from blood, and genotyping was performed by polymerase chain reaction. To measure the differences between the participating groups, Chi-squared test was performed using Statistica 9.0 for Windows® (significance level: p < 0.05). In comparing the ACE I/D allele frequencies, significant difference was detected between water polo (I = 61.11%; D = 38.89%) and combat sports (I = 35.71%, D = 64.29%) athletes (p < 0.03). There was no statistical difference when ACE I/D alleles in combat sports and kayaking/rowing (p > 0.05) were compared. A similarity was detectable in the I allele frequencies of the water polo (61.11%) and kayaking/rowing (56.67%) groups. The ACTN3 R/X polymorphism showed no differences in comparison with the sport groups. R allele frequencies were higher in every group compared to the X allele. The potential significance of the ACE I allele in sports of an aerobic nature was not clearly confirmed among Hungarian athletes.

  11. AGT and ACE genes influence classic mitral valve prolapse predisposition in Marfan patients.

    PubMed

    Fatini, Cinzia; Attanasio, Monica; Porciani, Cristina; Sticchi, Elena; Padeletti, Luigi; Lapini, Ilaria; Abbate, Rosanna; Gensini, Gian Franco; Pepe, Guglielmina

    2008-01-24

    In Marfan syndrome, the mitral valve prolapse, ranging from nonclassic to classic form on the basis of the leaflet thickness, is a common condition characterized by a highly variable structural abnormality. We investigated the role of angiotensinogen (AGT) M235T, angiotensin converting enzyme (ACE) I/D and angiotensin II type 1 receptor (AT1R) A1166C polymorphisms in influencing the susceptibility to classic or non-classic mitral valve prolapse in Marfan patients. We studied 135 Marfan patients with mitral valve prolapse, diagnosed by echocardiography. AGT, ACE, and AT1R polymorphisms were identified by polymerase chain reaction-based restriction analysis. The frequency of the ACE D, but not AGT 235T and AT1R 1166C allele, was significantly higher in patients with classic mitral valve prolapse in comparison to that observed in the non-classic one (p=0.03). The percentage of subjects with the contemporaneous presence of ACE D and AGT 235T alleles was significantly higher in the classic mitral valve prolapse group in comparison to the non-classic one (79% vs. 55%, respectively; p=0.008). The concomitant presence of these two alleles was associated with increased susceptibility to the classic mitral valve prolapse (OR 3.02, p=0.016). Our findings show a possible role of ACE and AGT genes as predisposing factors to classic mitral valve prolapse in Marfan patients, thus suggesting a role of renin angiotensin system genes in modulating mitral valve abnormality, and the need for an interventional study with angiotensin II type 1 receptor antagonists, which considers the leaflet thickness progression in Marfan patients with MVP.

  12. Molecular and Thermodynamic Mechanisms of the Chloride-dependent Human Angiotensin-I-converting Enzyme (ACE)*

    PubMed Central

    Yates, Christopher J.; Masuyer, Geoffrey; Schwager, Sylva L. U.; Akif, Mohd; Sturrock, Edward D.; Acharya, K. Ravi

    2014-01-01

    Somatic angiotensin-converting enzyme (sACE), a key regulator of blood pressure and electrolyte fluid homeostasis, cleaves the vasoactive angiotensin-I, bradykinin, and a number of other physiologically relevant peptides. sACE consists of two homologous and catalytically active N- and C-domains, which display marked differences in substrate specificities and chloride activation. A series of single substitution mutants were generated and evaluated under varying chloride concentrations using isothermal titration calorimetry. The x-ray crystal structures of the mutants provided details on the chloride-dependent interactions with ACE. Chloride binding in the chloride 1 pocket of C-domain ACE was found to affect positioning of residues from the active site. Analysis of the chloride 2 pocket R522Q and R522K mutations revealed the key interactions with the catalytic site that are stabilized via chloride coordination of Arg522. Substrate interactions in the S2 subsite were shown to affect chloride affinity in the chloride 2 pocket. The Glu403-Lys118 salt bridge in C-domain ACE was shown to stabilize the hinge-bending region and reduce chloride affinity by constraining the chloride 2 pocket. This work demonstrated that substrate composition to the C-terminal side of the scissile bond as well as interactions of larger substrates in the S2 subsite moderate chloride affinity in the chloride 2 pocket of the ACE C-domain, providing a rationale for the substrate-selective nature of chloride dependence in ACE and how this varies between the N- and C-domains. PMID:24297181

  13. Role of angiotensin-converting enzyme 2 (ACE2) in diabetic cardiovascular complications.

    PubMed

    Patel, Vaibhav B; Parajuli, Nirmal; Oudit, Gavin Y

    2014-04-01

    Diabetes mellitus results in severe cardiovascular complications, and heart disease and failure remain the major causes of death in patients with diabetes. Given the increasing global tide of obesity and diabetes, the clinical burden of diabetes-induced cardiovascular disease is reaching epidemic proportions. Therefore urgent actions are needed to stem the tide of diabetes which entails new prevention and treatment tools. Clinical and pharmacological studies have demonstrated that AngII (angiotensin II), the major effector peptide of the RAS (renin-angiotensin system), is a critical promoter of insulin resistance and diabetes mellitus. The role of RAS and AngII has been implicated in the progression of diabetic cardiovascular complications and AT1R (AngII type 1 receptor) blockers and ACE (angiotensin-converting enzyme) inhibitors have shown clinical benefits. ACE2, the recently discovered homologue of ACE, is a monocarboxypeptidase which converts AngII into Ang-(1-7) [angiotensin-(1-7)] which, by virtue of its actions on the MasR (Mas receptor), opposes the effects of AngII. In animal models of diabetes, an early increase in ACE2 expression and activity occurs, whereas ACE2 mRNA and protein levels have been found to decrease in older STZ (streptozotocin)-induced diabetic rats. Using the Akita mouse model of Type 1 diabetes, we have recently shown that loss of ACE2 disrupts the balance of the RAS in a diabetic state and leads to AngII/AT1R-dependent systolic dysfunction and impaired vascular function. In the present review, we will discuss the role of the RAS in the pathophysiology and treatment of diabetes and its complications with particular emphasis on potential benefits of the ACE2/Ang-(1-7)/MasR axis activation.

  14. Acute stress and cardiovascular health: is there an ACE gene connection?

    PubMed

    Holman, E Alison

    2012-10-01

    Cardiovascular disorders (CVD) are associated with acute and posttraumatic stress responses, yet biological processes underlying this association are poorly understood. This study examined whether renin-angiotensin-aldosterone system activity, as indicated by a functional single nucleotide polymorphism (SNP) in the angiotensin converting enzyme (ACE) gene, is associated with both CVD and acute stress related to the September 11, 2001 (9/11) terrorist attacks. European-American respondents (N = 527) from a nationally representative longitudinal study of coping following 9/11 provided saliva for genotyping. Respondents had completed health surveys before 9/11 and annually for 3 years after, and acute stress assessments 9 to 23 days after 9/11. Respondents with rs4291 AA or TT genotypes reported high acute stress twice as often as those with the AT genotype. Individuals with the TT genotype were 43% more likely to report increased physician-diagnosed CVD over 3 years following 9/11, when the following variables were included in the model: (a) pre-9/11 CVD, mental health, and non-CVD ailments; (b) cardiac risk factors; (c) ongoing endocrine disorders; and (d) significant demographics. The ACE rs4291 TT genotype, which has been associated with HPA axis hyperactivity and higher levels of serum angiotensin converting enzyme (ACE), predicted acute stress response and reports of physician-diagnosed CVD in a national sample following collective stress. ACE gene function may be associated with both mental and physical health disorders following collective stress. Copyright © 2012 International Society for Traumatic Stress Studies.

  15. Angiotensin converting enzyme gene polymorphism in familial hypertrophic cardiomyopathy patients

    SciTech Connect

    Yu, B; Peric, S.; Ross, D.

    1994-09-01

    An insertion/deletion (I/D) polymorphism of the angiotensin I converting enzyme (ACE) gene is a useful predictor of human plasma ACE levels. ACE levels tend to be lowest in subjects with ACE genotype DD and intermediate in subjects with ACE genotype ID. Angiotensin II (Ang II) as a product of ACE is a cardiac growth factor and produces a marked hypertrophy of the chick myocyte in cell culture. Rat experiments also suggest that a small dose of ACE inhibitor that does not affect the afterload results in prevention or regression of cardiac hypertrophy. In order to study the relationship of ACE and the severity of hypertrophy, the ACE genotype has been determined in 28 patients with a clinical diagnosis of familial hypertrophic cardiomyopathy (FHC) and 51 normal subjects. The respective frequencies of I and D alleles were: 0.52 and 0.48 (in FHC patients) and 0.44 and 0.56 (in the normal controls). There was no significant difference in the allele frequencies between FHC and normal subjects ({chi}{sup 2}=0.023, p>0.05). The II, ID, and DD genotypes were present in 7, 15, and 6 FHC patients, respectively. The averages of maximal thickness of the interventricular septum measured by echocardiography or at autopsy were 18 {plus_minus}3, 19{plus_minus}4, and 19{plus_minus}3 mm in II, ID and DD genotypes, respectively. The ACE gene polymorphism did not correlate with the severity of left ventricular hypertrophy in FHC patients (r{sub s}=0.231, p>0.05). These results do not necessarily exclude the possible effect of Ang II on the hypertrophy since the latter may be produced through the action of chymase in the human ventricles. However, ACE gene polymorphism is not a useful predictor of the severity of myocardial hypertrophy in FHC patients.

  16. A novel aggregation-induced emission based fluorescent probe for an angiotensin converting enzyme (ACE) assay and inhibitor screening.

    PubMed

    Wang, Haibo; Huang, Yi; Zhao, Xiaoping; Gong, Wan; Wang, Yi; Cheng, Yiyu

    2014-12-11

    A 'turn-on' fluorescent probe based on aggregation-induced emission (AIE) has been developed. It exhibits excellent selectivity and sensitivity for monitoring angiotensin converting enzyme (ACE) activity both in solutions and in living cells as well as for screening ACE inhibitors in vitro.

  17. Sperm-specific expression of angiotensin-converting enzyme (ACE) is mediated by a 91-base-pair promoter containing a CRE-like element.

    PubMed Central

    Howard, T; Balogh, R; Overbeek, P; Bernstein, K E

    1993-01-01

    The gene encoding the testis isozyme of angiotensin-converting enzyme (testis ACE) is one example of the many genes expressed uniquely during spermatogenesis. This protein is expressed by developing germ cells late in their development and results from the activation of a sperm-specific promoter that is located within intron 12 of the gene encoding the somatic isozyme of ACE. In vitro transcription, DNase footprinting, gel shift assays, and transgenic mouse studies have been used to define the minimal testes ACE promoter and to characterize DNA-protein interactions mediating germ cell-specific expression. These studies show that proper cell- and stage-specific expression of testis ACE requires only a small portion of the immediate upstream sequence extending to -91. A critical motif within this core promoter is a cyclic AMP-responsive element sequence that interacts with a testis-specific transactivating factor. Since this putative cyclic AMP-responsive element has been conserved within the testis ACE promoters of different species and is found at the same site in other genes that are expressed specifically in the testis, it may provide a common mechanism for the recognition of sperm-specific promoters. Images PMID:8380220

  18. New Perspectives in the Renin-Angiotensin-Aldosterone System (RAAS) II: Albumin Suppresses Angiotensin Converting Enzyme (ACE) Activity in Human

    PubMed Central

    Fagyas, Miklós; Úri, Katalin; Siket, Ivetta M.; Fülöp, Gábor Á.; Csató, Viktória; Daragó, Andrea; Boczán, Judit; Bányai, Emese; Szentkirályi, István Elek; Maros, Tamás Miklós; Szerafin, Tamás; Édes, István; Papp, Zoltán; Tóth, Attila

    2014-01-01

    About 8% of the adult population is taking angiotensin-converting enzyme (ACE) inhibitors to treat cardiovascular disease including hypertension, myocardial infarction and heart failure. These drugs decrease mortality by up to one-fifth in these patients. We and others have reported previously that endogenous inhibitory substances suppress serum ACE activity, in vivo, similarly to the ACE inhibitor drugs. Here we have made an effort to identify this endogenous ACE inhibitor substance. ACE was crosslinked with interacting proteins in human sera. The crosslinked products were immunoprecipitated and subjected to Western blot. One of the crosslinked products was recognized by both anti-ACE and anti-HSA (human serum albumin) antibodies. Direct ACE-HSA interaction was confirmed by binding assays using purified ACE and HSA. HSA inhibited human purified (circulating) and human recombinant ACE with potencies (IC50) of 5.7±0.7 and 9.5±1.1 mg/mL, respectively. Effects of HSA on the tissue bound native ACE were tested on human saphenous vein samples. Angiotensin I evoked vasoconstriction was inhibited by HSA in this vascular tissue (maximal force with HSA: 6.14±1.34 mN, without HSA: 13.54±2.63 mN), while HSA was without effects on angiotensin II mediated constrictions (maximal force with HSA: 18.73±2.17 mN, without HSA: 19.22±3.50 mN). The main finding of this study is that HSA was identified as a potent physiological inhibitor of the ACE. The enzymatic activity of ACE appears to be almost completely suppressed by HSA when it is present in its physiological concentration. These data suggest that angiotensin I conversion is limited by low physiological ACE activities, in vivo. PMID:24691203

  19. Automated multi-step purification protocol for Angiotensin-I-Converting-Enzyme (ACE).

    PubMed

    Eisele, Thomas; Stressler, Timo; Kranz, Bertolt; Fischer, Lutz

    2012-12-12

    Highly purified proteins are essential for the investigation of the functional and biochemical properties of proteins. The purification of a protein requires several steps, which are often time-consuming. In our study, the Angiotensin-I-Converting-Enzyme (ACE; EC 3.4.15.1) was solubilised from pig lung without additional detergents, which are commonly used, under mild alkaline conditions in a Tris-HCl buffer (50mM, pH 9.0) for 48h. An automation of the ACE purification was performed using a multi-step protocol in less than 8h, resulting in a purified protein with a specific activity of 37Umg(-1) (purification factor 308) and a yield of 23.6%. The automated ACE purification used an ordinary fast-protein-liquid-chromatography (FPLC) system equipped with two additional switching valves. These switching valves were needed for the buffer stream inversion and for the connection of the Superloop™ used for the protein parking. Automated ACE purification was performed using four combined chromatography steps, including two desalting procedures. The purification methods contained two hydrophobic interaction chromatography steps, a Cibacron 3FG-A chromatography step and a strong anion exchange chromatography step. The purified ACE was characterised by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) and native-PAGE. The estimated monomer size of the purified glycosylated ACE was determined to be ∼175kDa by SDS-PAGE, with the dimeric form at ∼330kDa as characterised by a native PAGE using a novel activity staining protocol. For the activity staining, the tripeptide l-Phe-Gly-Gly was used as the substrate. The ACE cleaved the dipeptide Gly-Gly, releasing the l-Phe to be oxidised with l-amino acid oxidase. Combined with peroxidase and o-dianisidine, the generated H(2)O(2) stained a brown coloured band. This automated purification protocol can be easily adapted to be used with other protein purification tasks. Copyright © 2012 Elsevier B.V. All rights

  20. New insight into the role of the Cdc34 ubiquitin-conjugating enzyme in cell cycle regulation via Ace2 and Sic1.

    PubMed

    Cocklin, Ross; Heyen, Joshua; Larry, Tolonda; Tyers, Mike; Goebl, Mark

    2011-03-01

    The Cdc34 ubiquitin-conjugating enzyme plays a central role in progression of the cell cycle. Through analysis of the phenotype of a mutant missing a highly conserved sequence motif within the catalytic domain of Cdc34, we discovered previously unrecognized levels of regulation of the Ace2 transcription factor and the cyclin-dependent protein kinase inhibitor Sic1. In cells carrying the Cdc34(tm) mutation, which alters the conserved sequence, the cyclin-dependent protein kinase inhibitor Sic1, an SCF(Cdc4) substrate, has a shorter half-life, while the cyclin Cln1, an SCF(Grr1) substrate, has a longer half-life than in wild-type cells. Expression of the SIC1 gene cluster, which is regulated by Swi5 and Ace2 transcription factors, is induced in CDC34(tm) cells. Levels of Swi5, Ace2, and the SCF(Grr1) targets Cln1 and Cln2 are elevated in Cdc34(tm) cells, and loss of Grr1 causes an increase in Ace2 levels. Sic1 levels are similar in CDC34(tm) ace2Δ and wild-type cells, explaining a paradoxical increase in the steady-state level of Sic1 protein despite its reduced half-life. A screen for mutations that interact with CDC34(tm) uncovered novel regulators of Sic1, including genes encoding the polyubiquitin chain receptors Rad23 and Rpn10. © 2011 by the Genetics Society of America

  1. Isolation and antihypertensive effect of angiotensin I-converting enzyme (ACE) inhibitory peptides from spinach Rubisco.

    PubMed

    Yang, Yanjun; Marczak, Ewa D; Yokoo, Megumi; Usui, Hachiro; Yoshikawa, Masaaki

    2003-08-13

    Four new inhibitory peptides for angiotensin I-converting enzyme (ACE), that is, MRWRD, MRW, LRIPVA, and IAYKPAG, were isolated from the pepsin-pancreatin digest of spinach Rubisco with the use of HPLC. IC(50) values of individual peptides were 2.1, 0.6, 0.38, and 4.2 microM, respectively. MRW and MRWRD had an antihypertensive effect after oral administration to spontaneously hypertensive rats. Maximal reduction occurred 2 h after oral administration of MRW, whereas MRWRD showed maximal decrease 4 h after oral administration at doses of 20 and 30 mg/kg, respectively. IAYKPAG also exerted antihypertensive activity after oral administration at the dose of 100 mg/kg, giving a maximum decrease 4 h after oral administration. IAYKP, IAY, and KP, the fragment peptides of IAYKPAG, also exerted antihypertensive activity. LRIPVA [corrected] did not show any antihypertensive effect at a dose of 100 mg/kg despite its potent ACE-inhibitory activity.

  2. Sex-Specific Changes in Renal Angiotensin-Converting Enzyme and Angiotensin-Converting Enzyme 2 Gene Expression and Enzyme Activity at Birth and Over the First Year of Life.

    PubMed

    Chen, Kai; Bi, Jianli; Su, Yixin; Chappell, Mark C; Rose, James C

    2016-02-01

    Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) are key enzymes of the renin-angiotensin system. We investigated developmental changes in renal ACE and ACE2 gene expression and activity in both male and female sheep. Three groups of sheep (fetus, newborn, and adult) were used. Renal ACE and ACE2 activities, messenger RNA (mRNA), and protein expression were studied. Renal ACE and ACE2 activities increased at 1 year in males, while there were no changes throughout development in females. Renal ACE and ACE2 mRNA and protein showed no sex differences but increased by 1 year of age. There are sex-related differences in the development of renal-converting enzyme activities that may have functional implications in terms of the regulation of blood pressure and renal function in men and women. The difference in the patterns of gene expression and enzyme activity indicates that changes in gene expression may not accurately reflect changes in activity. © The Author(s) 2015.

  3. Modification of Epigenetic Patterns in Low Birth Weight Children: Importance of Hypomethylation of the ACE Gene Promoter

    PubMed Central

    Rangel, Marina; dos Santos, Jéssica Cassilla; Ortiz, Paula Helena Lima; Hirata, Mario; Jasiulionis, Miriam Galvonas; Araujo, Ronaldo C.; Ierardi, Daniela Filippini; Franco, Maria do Carmo

    2014-01-01

    There is a growing body of evidence that epigenetic alterations are involved in the pathological mechanisms of many chronic disorders linked to fetal programming. Angiotensin-converting enzyme (ACE) appears as one candidate gene that brings new insights into the epigenetic control and later development of diseases. In this view, we have postulated that epigenetic modifications in the ACE gene might show different interactions between birth weight (BW), blood pressure levels, plasma ACE activity and ACE I/D polymorphism. To explore this hypothesis, we performed a cross-sectional study to evaluate the DNA methylation of 3 CpG sites using pyrosequencing within the ACE gene promoter of peripheral blood leukocytes from 45 LBW children compared with 70 NBW children. Our results have revealed that LBW children have lower methylation levels (P<0.001) in parallel with a higher ACE activity (P = 0.001). Adjusting for prematurity, gender, age, body mass index, and family history of cardiovascular disease did not alter these findings. We have also performed analyses of individual CpG sites. The frequency of DNA methylation was significantly different at two CpG sites (site 1: nucleotide position +555; and site 3: nucleotide position +563). In addition, we have found a significant inverse correlation between degree of DNA methylation and both ACE activity (P<0.001) and systolic blood pressure levels (P<0.001). We also observed that the methylation level was significantly lower in LBW children who are carriers of the DD genotype compared to NBW children with DD genotype (P<0.024). In conclusion, we are able to demonstrate that the hypomethylation in the 3 CpG sites of ACE gene promoter is associated with LBW in 6 to 12 year-old children. The magnitude of these epigenetic changes appears to be clinically important, which is supported by the observation that discrete changes in DNA methylation can affect systolic blood pressure and ACE protein activity levels. PMID:25170764

  4. Synthesis and evaluation of novel triazoles and mannich bases functionalized 1,4-dihydropyridine as angiotensin converting enzyme (ACE) inhibitors.

    PubMed

    Kumbhare, Ravindra M; Kosurkar, Umesh B; Bagul, Pankaj K; Kanwal, Abhinav; Appalanaidu, K; Dadmal, Tulshiram L; Banerjee, Sanjay Kumar

    2014-11-01

    A series of novel diethyl 2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate embedded triazole and mannich bases were synthesized, and evaluated for their angiotensin converting enzyme (ACE) inhibitory activity. Screening of above synthesized compounds for ACE inhibition showed that triazoles functionalized compounds have better ACE inhibitory activity compared to that of mannich bases analogues. Among all triazoles we found 6 h, 6 i and 6 j to have good ACE inhibition activity with IC50 values 0.713 μM, 0.409 μM and 0.653 μM, respectively. Among mannich bases series compounds, only 7c resulted as most active ACE inhibitor with IC50 value of 0.928 μM.

  5. Identification of a new angiotensin-converting enzyme (ACE) inhibitor from Thai edible plants.

    PubMed

    Simaratanamongkol, Arunee; Umehara, Kaoru; Noguchi, Hiroshi; Panichayupakaranant, Pharkphoom

    2014-12-15

    Eight Thai edible plants were tested for their inhibitory activity against an angiotensin-converting enzyme (ACE) using an in vitro assay. The methanol extract of Apium graveolens exhibited significant ACE inhibitory activity with an IC50 value of 1.7 mg/ml, and was then subjected to an isolation procedure that resulted in identification of a pure active constituent, junipediol A 8-O-β-d-glucoside (1-β-d-glucosyloxy-2-(3-methoxy-4-hydroxyphenyl)-propane-1,3-diol) (1), which had good ACE inhibitory activity with an IC50 value of 76 μg/ml. Another eight known compounds, isofraxidin-β-d-glucoside (2), roseoside (3), apigenin-7-O-β-d-glucoside (4), luteolin-7-O-β-d-glucoside (5), icariside D2 (6), apiin (7), chrysoeriol-7-O-β-d-apiosylglucoside (8), and 11,21-dioxo-3 β,15 α,24-trihydroxyurs-12-ene-24-O-β-d-glucopyranoside (9) were also identified. Although each of these five constituents (2-6) isolated from the same fraction as 1 showed no activity at concentrations of 500 μM, together, when each was present at 300 μg/ml, they enhanced the inhibitory activity of 500 μM of 1 from 64% to 81%. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Production of Angiotensin I Converting Enzyme Inhibitory (ACE-I) Peptides during Milk Fermentation and Their Role in Reducing Hypertension.

    PubMed

    Rai, Amit Kumar; Sanjukta, Samurailatpam; Jeyaram, Kumaraswamy

    2015-10-13

    Fermented milk is a potential source of various biologically active peptides with specific health benefits. Angiotensin converting enzyme inhibitory (ACE-I) peptides are one of the most studied bioactive peptides produced during milk fermentation. The presence of these peptides is reported in various fermented milk products such as yoghurt, cheese, sour milk, etc, which are also available as commercial products. Many of the ACE-I peptides formed during milk fermentation are resistant to gastrointestinal digestion and inhibit angiotensin converting enzyme (ACE) in the rennin angiotension system (RAS). There are various factors, which affect the formation ACE-I peptides and their ability to reach the target tissue in active form, which includes type of starters (lactic acid bacteria, yeast, etc), substrate composition (casein type, whey protein, etc), composition of ACE-I peptide, pre and post fermentation treatments, and its stability during gastrointestinal digestion. The antihypertensive effect of fermented milk products has also been proved by various in-vitro and in-vivo (animal and human trials) experiments. This article reviews the literature on fermented milk products as a source of ACE-I peptides and various factors affecting the production and activity of ACE-I peptides.

  7. Endometriosis and RAS system gene polymorphisms: the association of ACE A2350G polymorphism with endometriosis in Polish individuals.

    PubMed

    Kowalczyńska, Liliana J; Ferenc, Tomasz; Wojciechowski, Michał; Mordalska, Anna; Pogoda, Krzysztof; Malinowski, Andrzej

    2014-05-01

    To analyze the polymorphisms of angiotensin I converting enzyme (ACE) gene (insertion/deletion [I/D], A2350G) and angiotensin II type 1 receptor gene (A1166C) in women with endometriosis and to determine the correlation of the identified genotypes with the severity of the disease. Additionally, to estimate the prognostic value of the polymorphisms in patients with endometriosis treated due to infertility. The study group included 241 women, the control group (without endometriosis)-127. The molecular analysis was performed by polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism technique. For I/D ACE and A1166C AT1 polymorphisms no significant differences were observed between the study and control groups and between the severity grades of the disease (p>0.05). For A2350G ACE polymorphism the frequency of genotypes for the study and control groups respectively was the following: AA-31.54%, AG-54.36%, GG-14.11% and AA-55.12%, AG-36.22%, GG-8.66% (x(2)=19.36, p<0.0001). Statistically significant differences were found between the frequency of A and G alleles between both groups (x(2)=15.16, p=0.0001), but not when individual grades of the disease severity were compared. There was no association between the investigated polymorphisms and the effect of infertility treatment. A2350G polymorphism (allele G, AG genotype) of ACE gene seems to be associated with the development of endometriosis.

  8. Impact of I/D polymorphism of ACE gene on risk of development and course of chronic obstructive pulmonary disease

    PubMed Central

    Homa-Mlak, Iwona; Powrózek, Tomasz; Mackiewicz, Barbara; Michnar, Marek; Krawczyk, Paweł; Dziedzic, Marcin; Rubinsztajn, Renata; Chazan, Ryszarda; Milanowski, Janusz; Małecka-Massalska, Teresa

    2016-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) affects more than 10% of the world's population over 40 years of age. The main exogenous risk factor is cigarette smoking; however, only 20% of smokers develop COPD, indicating that some other factors, e.g. genetic, may play an important role in the disease pathogenesis. Recent research indicates that ACE (angiotensin-converting enzyme) may be a susceptibility gene for asthma or COPD. The aim of our study was to determine the influence of I/D (insertion/deletion) polymorphism of the ACE gene (AluYa5, rs4646994) on the risk and course of COPD. Material and methods We investigated ACE I/D polymorphism in 206 COPD and 165 healthy Caucasian subjects. Results In the generalized linear model (GLZ) analysis of the influence of selected factors on presence of COPD we found a significant independent effect for male sex (repeatedly increases the risk of COPD, OR = 7.7, p = 0.049), as well as smoking or lower body mass index, but only in combination with older age (OR = 0.96, p = 0.003 and OR = 1.005, p = 0.04 respectively). Interestingly, analysis of factors which may influence the risk of a higher number of exacerbations demonstrated that occurrence of DD genotype, but only in men, is associated with a lower risk (OR = 0.7, p = 0.03) of this complication. Conclusions We suggest that ACE may not be a susceptibility gene for the origin of COPD but a disease-modifying gene. Since the impact of I/D polymorphism of the ACE gene on COPD risk is moderate or negligible, other molecular changes, that will help predict the development of this disease, should still be sought. PMID:27186170

  9. Mutations in Escherichia coli aceE and ribB genes allow survival of strains defective in the first step of the isoprenoid biosynthesis pathway.

    PubMed

    Perez-Gil, Jordi; Uros, Eva Maria; Sauret-Güeto, Susanna; Lois, L Maria; Kirby, James; Nishimoto, Minobu; Baidoo, Edward E K; Keasling, Jay D; Boronat, Albert; Rodriguez-Concepcion, Manuel

    2012-01-01

    A functional 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway is required for isoprenoid biosynthesis and hence survival in Escherichia coli and most other bacteria. In the first two steps of the pathway, MEP is produced from the central metabolic intermediates pyruvate and glyceraldehyde 3-phosphate via 1-deoxy-D-xylulose 5-phosphate (DXP) by the activity of the enzymes DXP synthase (DXS) and DXP reductoisomerase (DXR). Because the MEP pathway is absent from humans, it was proposed as a promising new target to develop new antibiotics. However, the lethal phenotype caused by the deletion of DXS or DXR was found to be suppressed with a relatively high efficiency by unidentified mutations. Here we report that several mutations in the unrelated genes aceE and ribB rescue growth of DXS-defective mutants because the encoded enzymes allowed the production of sufficient DXP in vivo. Together, this work unveils the diversity of mechanisms that can evolve in bacteria to circumvent a blockage of the first step of the MEP pathway.

  10. Radiation damage to the lung: mitigation by angiotensin converting enzyme (ACE) inhibitors

    PubMed Central

    Medhora, Meetha; Gao, Feng; Jacobs, Elizabeth R.; Moulder, John E.

    2011-01-01

    Concern regarding accidental overexposure to radiation has been raised after the devastating Tohuku earthquake and tsunami which initiated the Fukushima Daiichi nuclear disaster in Japan, in March 2011. Radiation exposure is toxic and can be fatal depending on the dose received. Injury to the lung is often reported as part of multi-organ failure in victims of accidental exposures. Doses of radiation >8 Gray to the chest can induce pneumonitis with right ventricular hypertrophy starting after ~2 months. Higher doses may be followed by pulmonary fibrosis that presents months to years after exposure. Though the exact mechanisms of radiation lung damage are not known, experimental animal models have been widely used to study this injury. Rodent models for pneumonitis and fibrosis exhibit vascular, parenchymal and pleural injuries to the lung. Inflammation is a part of the injuries suggesting involvement of the immune system. Researchers world-wide have tested a number of interventions to prevent or mitigate radiation lung injury. One of the first and most successful class of mitigators are inhibitors of angiotensin converting enzyme (ACE), an enzyme that is abundant in the lung. These results offer hope that lung injury from radiation accidents may be mitigated, since the ACE inhibitor captopril was effective when started up to one week after irradiation. PMID:22023053

  11. Does the cis/trans configuration of peptide bonds in bioactive tripeptides play a role in ACE-1 enzyme inhibition?

    PubMed Central

    Siltari, Aino; Viitanen, Riikka; Kukkurainen, Sampo; Vapaatalo, Heikki; Valjakka, Jarkko

    2014-01-01

    Background The milk casein-derived bioactive tripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP) have been shown to prevent development of hypertension in animal models and to lower blood pressure in moderately hypertensive subjects in most but not all clinical trials. Inhibition of angiotensin-converting enzyme 1 (ACE-1) has been suggested as the explanation for these antihypertensive and beneficial vascular effects. Previously, human umbilical vein endothelial cells (HUVEC) have not been used to test ACE-1 inhibiting properties of casein derived tripeptides in vasculature. Purpose We focused on the cis/trans configurations of the peptide bonds in proline-containing tripeptides in order to discover whether the different structural properties of these peptides influence their activity in ACE-1 inhibition. We hypothesized that the configuration of proline-containing peptides plays a significant role in enzyme inhibition. Methods AutoDock 4.2 docking software was used to predict suitable peptide bond configurations of the tripeptides. Besides modeling studies, we completed ACE-1 activity measurements in vitro using HUVEC cultures. Results In HUVEC cells, both IPP and VPP inhibited ACE-1. Based on molecular docking studies, we propose that in ACE-1 inhibition IPP and VPP share a similar cis configuration between the first aliphatic (isoleucine or valine) and the second (proline) amino acid residues and more different configurations between two proline residues. In vivo experiments are needed to validate the significance of the present findings. PMID:24596454

  12. An ace-1 gene duplication resorbs the fitness cost associated with resistance in Anopheles gambiae, the main malaria mosquito

    PubMed Central

    Assogba, Benoît S.; Djogbénou, Luc S.; Milesi, Pascal; Berthomieu, Arnaud; Perez, Julie; Ayala, Diego; Chandre, Fabrice; Makoutodé, Michel; Labbé, Pierrick; Weill, Mylène

    2015-01-01

    Widespread resistance to pyrethroids threatens malaria control in Africa. Consequently, several countries switched to carbamates and organophophates insecticides for indoor residual spraying. However, a mutation in the ace-1 gene conferring resistance to these compounds (ace-1R allele), is already present. Furthermore, a duplicated allele (ace-1D) recently appeared; characterizing its selective advantage is mandatory to evaluate the threat. Our data revealed that a unique duplication event, pairing a susceptible and a resistant copy of the ace-1 gene spread through West Africa. Further investigations revealed that, while ace-1D confers less resistance than ace-1R, the high fitness cost associated with ace-1R is almost completely suppressed by the duplication for all traits studied. ace-1 duplication thus represents a permanent heterozygote phenotype, selected, and thus spreading, due to the mosaic nature of mosquito control. It provides malaria mosquito with a new evolutionary path that could hamper resistance management. PMID:26434951

  13. Cleavage of arginyl-arginine and lysyl-arginine from the C-terminus of pro-hormone peptides by human germinal angiotensin I-converting enzyme (ACE) and the C-domain of human somatic ACE.

    PubMed Central

    Isaac, R E; Williams, T A; Sajid, M; Corvol, P; Coates, D

    1997-01-01

    Mammalian germinal angiotensin I-converting enzyme (gACE) is a single-domain dipeptidyl carboxypeptidase found exclusively in male germ cells, which has almost identical sequence and enzymic properties with the C-domain of the two-domain somatic ACE. Mutant mice that do not express gACE are infertile, suggesting a role for the enzyme in the processing of undefined peptides involved in fertilization. A number of spermatid peptides [e.g. cholecystokinin (CCK) and gastrin] are processed from pro-hormones by endo- and exo-proteolytic cleavages which might generate substrates for gACE. We have shown that peptide hormone intermediates with Lys/Arg-Arg at the C-terminus are high-affinity substrates for human gACE. gACE from human sperm cleaved Arg-Arg from the C-terminus of the CCK5-GRR (GWMDFGRR), a peptide corresponding to the C-terminus of a CCK-gastrin prohormone intermediate. Hydrolysis of CCK5-GRR by recombinant human C-domain ACE was Cl- dependent, with maximal activity achieved in 5-10 mM NaCl at pH 6.4. C-Domain ACE cleaved Lys/Arg-Arg from the C-terminus of dynorphin-(1-7), a pro-TRH peptide KRQHPGKR, and two insect peptides FSPRLGKR and FSPRLGRR. C-Domain ACE displayed high affinity towards all these substrates with Vmax/Km values between 14 and 113 times greater than the Vmax/Km for the conversion of the best known ACE substrate, angiotensin I, into angiotensin II. In conclusion, we have identified a new class of substrates for human gACE, and we suggest that gACE might be an alternative to carboxypeptidase E for the trimming of basic dipeptides from the C-terminus of intermediates generated from pro-hormones by subtilisin-like convertases in human male germ cells. PMID:9371719

  14. Combined "pro-atherosclerotic" variants of the ACE and APOE genes increase the risk of the coronary artery disease associated with the presence of cigarette smoking.

    PubMed

    Zak, Iwona; Niemiec, Pawel; Balcerzyk, Anna; Krauze, Jolanta

    2008-12-01

    Cigarette smoking increases the synthesis of angiotensin-1 converting enzyme (ACE) and induces oxidative modifications of the apolipoprotein E (apo E).Thus we explored the gene-environment interactions between APOE gene epsilon and ACE gene insertion/deletion polymorphisms and cigarette smoking in coronary artery disease (CAD) patients. We analysed 360 subjects: 171 CAD patients and 189 blood donors without a history of cardiovascular diseases. ACE and APOE polymorphisms were genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods, respectively. To determine gene-environment interactions, epidemiological methodology was used. The ACE DD genotype was a rather weak risk factor of CAD in the analysed population (OR = 1.87, P = 0.01).The differences in allele and genotype distribution of the APOE polymorphism were not statistically significant.The carriers of the combined genotype ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) were more frequent in patients, however, the differences were on the bound of statistical significance (P = 0.08). Logistic regression analysis showed that the ACE(DD) + apo E(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) cigarette smokers were much more frequent in the CAD group (OR = 11.68, 95%CI; 1.52-246.43, P = 0.009).We confirmed these results using the 4 x 2 table approach and we found a synergistic effect of the ACE(DD) + APOE(epsilon4epsilon4,epsilon3epsilon4,epsilon2epsilon4) combined genotype and cigarette smoking (SI = 10.52, SIM = 6.09). We demonstrated the existence of the synergistic effect between cigarette smoking and the contemporaneous carrier-state of APOE epsilon4 and ACE D alleles which increased the risk of CAD to a large extent.

  15. Determining the Enzymatic Activity of Angiotensin-Converting Enzyme 2 (ACE2) in Brain Tissue and Cerebrospinal Fluid Using a Quenched Fluorescent Substrate.

    PubMed

    Sriramula, Srinivas; Pedersen, Kim Brint; Xia, Huijing; Lazartigues, Eric

    2017-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a component of the renin-angiotensin system (RAS) which plays an important role in the regulation of blood pressure and volume homeostasis. Accumulating evidence shows alterations in ACE2 expression and activity in several hypertensive animal models, as well as in patients with hypertension. In order to assess the role of brain ACE2 in hypertension, a specific ACE2 assay is required. Based on a quenched fluorescent substrate, we describe an easy-to-use method for determining ACE2 activity in brain tissue and cerebrospinal fluid. The method can further be adapted for other tissues, plasma, cell extracts, and cell culture supernatants.

  16. The linkage disequilibrium pattern of the angiotensin converting enzyme gene in Arabic and Asian population groups.

    PubMed

    Kharrat, Najla; Abdelmouleh, Wafa; Abdelhedi, Rania; Alfadhli, Suad; Rebai, Ahmed

    2012-01-01

    DNA variations within the Angiotensin-Converting Enzyme (ACE) gene have been shown to be involved in the aetiology of several common diseases and the therapeutic response. This study reports a comparison of haplotype analysis of five SNPs in the ACE gene region using a sample of 100 healthy subjects derived from five different populations (Tunisian, Iranian, Kuwaiti, Bahraini and Indian). Strong linkage disequilibrium was found among all SNPs studied for all populations. Two SNPs (rs1800764 and rs4340) were identified as key SNPs for all populations. These SNPs will be valuable for future effective association studies of the ACE gene polymorphisms in Arab and Asian populations.

  17. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia.

    PubMed

    Shunmugam, Vicneswari; Say, Yee-How

    2016-02-01

    α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population. Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype.

  18. Genetic polymorphism of ACE and the angiotensin II type1 receptor genes in children with chronic kidney disease

    PubMed Central

    2011-01-01

    Aim and Methods We investigated the association between polymorphisms of the angiotensin converting enzyme-1 (ACE-1) and angiotensin II type one receptor (AT1RA1166C) genes and the causation of renal disease in 76 advanced chronic kidney disease (CKD) pediatric patients undergoing maintenance hemodialysis (MHD) or conservative treatment (CT). Serum ACE activity and creatine kinase-MB fraction (CK-MB) were measured in all groups. Left ventricular mass index (LVMI) was calculated according to echocardiographic measurements. Seventy healthy controls were also genotyped. Results The differences of D allele and DI genotype of ACE were found significant between MHD group and the controls (p = 0.0001). ACE-activity and LVMI were higher in MHD, while CK-MB was higher in CT patients than in all other groups. The combined genotype DD v/s ID+II comparison validated that DD genotype was a high risk genotype for hypertension .~89% of the DD CKD patients were found hypertensive in comparison to ~ 61% of patients of non DD genotype(p = 0.02). The MHD group showed an increased frequency of the C allele and CC genotype of the AT1RA1166C polymorphism (P = 0.0001). On multiple linear regression analysis, C-allele was independently associated with hypertension (P = 0.04). Conclusion ACE DD and AT1R A/C genotypes implicated possible roles in the hypertensive state and in renal damage among children with ESRD. This result might be useful in planning therapeutic strategies for individual patients. PMID:21859496

  19. Functional analysis of the human somatic angiotensin I-converting enzyme gene promoter.

    PubMed

    Testut, P; Soubrier, F; Corvol, P; Hubert, C

    1993-08-01

    Angiotensin I-converting enzyme (ACE) is a key enzyme in the regulation of systemic blood pressure and plays a major role in the renin-angiotensin and bradykinin-kinin systems, at the luminal surface of the vascular endothelia. To identify the promoter region, the transcription regulatory elements and the cell specificity of the ACE gene, five successive DNA deletions of the 5' upstream region (-1214, -754, -472, -343, -132 bp relative to the start site of transcription) were isolated and fused in sense and antisense orientations to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene in the promoterless plasmid pBLCAT3. Promoter activities were measured in transient transfection assays using three different cell lines from rabbit endothelium (RE), human embryocarcinoma (Tera-1) and hepatocarcinoma cells (HepG2). All five fragments of the ACE promoter region directed expression of the CAT gene when transfected into the endothelial and the embryocarcinoma cells, which contain endogenous ACE mRNA and express ACE activity. In contrast only minimal levels of promoter activity were obtained on transfection into hepatocarcinoma cells in which endogenous ACE mRNA and ACE activity were not detected. Transfection of RE and Tera-1 cells demonstrated that promoter activity was defined by the length of the ACE promoter sequence inserted into the construct. The 132 bases located upstream from the transcription start site were sufficient to confer ACE promoter activity, whereas the sequences upstream from -472 bp and between -343 bp and -132 bp were responsible for a decrease of promoter activity. Furthermore, the minimal 132 bp of the ACE promoter contains elements which direct cell-specific CAT expression. In addition, the DNA transfection study in the presence of dexamethasone suggested that the potential glucocorticoid regulatory elements, located in the sequence of the ACE promoter, are not functional.

  20. Functional analysis of the human somatic angiotensin I-converting enzyme gene promoter.

    PubMed Central

    Testut, P; Soubrier, F; Corvol, P; Hubert, C

    1993-01-01

    Angiotensin I-converting enzyme (ACE) is a key enzyme in the regulation of systemic blood pressure and plays a major role in the renin-angiotensin and bradykinin-kinin systems, at the luminal surface of the vascular endothelia. To identify the promoter region, the transcription regulatory elements and the cell specificity of the ACE gene, five successive DNA deletions of the 5' upstream region (-1214, -754, -472, -343, -132 bp relative to the start site of transcription) were isolated and fused in sense and antisense orientations to the bacterial chloramphenicol acetyltransferase (CAT) reporter gene in the promoterless plasmid pBLCAT3. Promoter activities were measured in transient transfection assays using three different cell lines from rabbit endothelium (RE), human embryocarcinoma (Tera-1) and hepatocarcinoma cells (HepG2). All five fragments of the ACE promoter region directed expression of the CAT gene when transfected into the endothelial and the embryocarcinoma cells, which contain endogenous ACE mRNA and express ACE activity. In contrast only minimal levels of promoter activity were obtained on transfection into hepatocarcinoma cells in which endogenous ACE mRNA and ACE activity were not detected. Transfection of RE and Tera-1 cells demonstrated that promoter activity was defined by the length of the ACE promoter sequence inserted into the construct. The 132 bases located upstream from the transcription start site were sufficient to confer ACE promoter activity, whereas the sequences upstream from -472 bp and between -343 bp and -132 bp were responsible for a decrease of promoter activity. Furthermore, the minimal 132 bp of the ACE promoter contains elements which direct cell-specific CAT expression. In addition, the DNA transfection study in the presence of dexamethasone suggested that the potential glucocorticoid regulatory elements, located in the sequence of the ACE promoter, are not functional. Images Figure 1 Figure 3 PMID:8394696

  1. Multi-Species Comparative Analysis of the Equine ACE Gene Identifies a Highly Conserved Potential Transcription Factor Binding Site in Intron 16

    PubMed Central

    Hamilton, Natasha A.; Tammen, Imke; Raadsma, Herman W.

    2013-01-01

    Angiotensin converting enzyme (ACE) is essential for control of blood pressure. The human ACE gene contains an intronic Alu indel (I/D) polymorphism that has been associated with variation in serum enzyme levels, although the functional mechanism has not been identified. The polymorphism has also been associated with cardiovascular disease, type II diabetes, renal disease and elite athleticism. We have characterized the ACE gene in horses of breeds selected for differing physical abilities. The equine gene has a similar structure to that of all known mammalian ACE genes. Nine common single nucleotide polymorphisms (SNPs) discovered in pooled DNA were found to be inherited in nine haplotypes. Three of these SNPs were located in intron 16, homologous to that containing the Alu polymorphism in the human. A highly conserved 18 bp sequence, also within that intron, was identified as being a potential binding site for the transcription factors Oct-1, HFH-1 and HNF-3β, and lies within a larger area of higher than normal homology. This putative regulatory element may contribute to regulation of the documented inter-individual variation in human circulating enzyme levels, for which a functional mechanism is yet to be defined. Two equine SNPs occurred within the conserved area in intron 16, although neither of them disrupted the putative binding site. We propose a possible regulatory mechanism of the ACE gene in mammalian species which was previously unknown. This advance will allow further analysis leading to a better understanding of the mechanisms underpinning the associations seen between the human Alu polymorphism and enzyme levels, cardiovascular disease states and elite athleticism. PMID:23408978

  2. Role of ACE and AGT gene polymorphisms in genetic susceptibility to diabetes mellitus type 2 in a Brazilian sample.

    PubMed

    Wollinger, L M; Dal Bosco, S M; Rempe, C; Almeida, S E M; Berlese, D B; Castoldi, R P; Arndt, M E; Contini, V; Genro, J P

    2015-12-29

    The aim of the current study was to investigate the association between the InDel polymorphism in the angiotensin I-converting enzyme gene (ACE) and the rs699 polymorphism in the angiotensinogen gene (AGT) and diabetes mellitus type 2 (DM2) in a sample population from Southern Brazil. A case-control study was conducted with 228 patients with DM2 and 183 controls without DM2. The ACE InDel polymorphism was genotyped by polymerase chain reaction (PCR) with specific primers, followed by electrophoresis on 1.5% agarose gel. The AGT rs699 polymorphism was genotyped using a real-time PCR assay. No significant association between the ACE InDel polymorphism and DM2 was detected (P = 0.97). However, regarding the AGT rs699 polymorphism, DM2 patients had a significantly higher frequency of the AG genotype and lower frequency of the GG genotype when compared to the controls (P = 0.03). Our results suggest that there is an association between the AGT rs699 polymorphism and DM2 in a Brazilian sample.

  3. Polymorphisms in NOS3, ACE and PAI-1 genes and risk of spontaneous recurrent miscarriage in the Gaza Strip.

    PubMed

    Al Sallout, Rami J; Sharif, Fadel A

    2010-01-01

    This study was conducted to investigate the correlation between spontaneous recurrent miscarriage (RM) and common polymorphisms in angiotensin-converting enzyme (ACE), plasminogen activator inhibitor 1 (PAI-1) and endothelium-derived nitric oxide synthase 3 (NOS3) genes among women experiencing RM in the Gaza Strip. The presence of these genetic profiles was determined for 100 women who had had at least 3 constitutive abortions and 100 controls without any history of abortion using molecular biological techniques. The ACE D/D polymorphism was present in 49% of the study population and in 54% of the controls (p = 0.479). Similarly, there was no significant difference detected in the distribution of polymorphisms for PAI-1, with the 4G/4G genotype present in the study group and in controls (p = 1.00). NOS3 4a/4a was present in 4% of the study group and in none of the 100 controls (p = 0.123). In this study, we also discovered a new variant in the NOS3 gene which was named 4c allele and was encountered in 1 patient and in 1 control subject. There was no significant association between ACE I/D, PAI-1 4G/5G and NOS3 4a/4b and the occurrence of first-trimester RM. In-depth investigation of the association of NOS3 4a/4a with RM is strongly recommended. Copyright 2010 S. Karger AG, Basel.

  4. Synthesis and biological studies of highly concentrated lisinopril-capped gold nanoparticles for CT tracking of angiotensin converting enzyme (ACE)

    NASA Astrophysics Data System (ADS)

    Ghann, William E.; Aras, Omer; Fleiter, Thorsten; Daniel, Marie-Christine

    2011-05-01

    For patients with a history of heart attack or stroke, the prevention of another cardiovascular or cerebrovascular event is crucial. The development of cardiac and pulmonary fibrosis has been associated with overexpression of tissue angiotensin-converting enzyme (ACE). Recently, gold nanoparticles (GNPs) have shown great potential as X-ray computed tomography (CT) contrast agents. Since lisinopril is an ACE inhibitor, it has been used as coating on GNPs for targeted imaging of tissue ACE in prevention of fibrosis. Herein, lisinopril-capped gold nanoparticles (LIS-GNPs) were synthesized up to a concentration of 55 mgAu/mL. Their contrast was measured using CT and the results were compared to Omnipaque, a commonly used iodine-based contrast agent. The targeting ability of these LIS-GNPs was also assessed.

  5. Angiotensin I-converting enzyme (ACE) activity and expression in rat central nervous system after sleep deprivation.

    PubMed

    Visniauskas, Bruna; Oliveira, Vitor; Carmona, Adriana K; D'Almeida, Vânia; de Melo, Robson L; Tufik, Sérgio; Chagas, Jair R

    2011-04-01

    Proteases are essential either for the release of neuropeptides from active or inactive proteins or for their inactivation. Neuropeptides have a fundamental role in sleep-wake cycle regulation and their actions are also likely to be regulated by proteolytic processing. Using fluorescence resonance energy transfer substrates, specific protease inhibitors and real-time PCR we demonstrate changes in angiotensin I-converting enzyme (ACE) expression and proteolytic activity in the central nervous system in an animal model of paradoxical sleep deprivation during 96 h (PSD). Male rats were distributed into five groups (PSD, 24 h, 48 h and 96 h of sleep recovery after PSD and control). ACE activity and mRNA levels were measured in hypothalamus, hippocampus, brainstem, cerebral cortex and striatum tissue extracts. In the hypothalamus, the significant decrease in activity and mRNA levels, after PSD, was only totally reversed after 96 h of sleep recovery. In the brainstem and hippocampus, although significant, changes in mRNA do not parallel changes in ACE specific activity. Changes in ACE activity could affect angiotensin II generation, angiotensin 1-7, bradykinin and opioid peptides metabolism. ACE expression and activity modifications are likely related to some of the physiological changes (cardiovascular, stress, cognition, metabolism function, water and energy balance) observed during and after sleep deprivation.

  6. Individual and combined influence of ACE and ACTN3 genes on muscle phenotypes in Polish athletes.

    PubMed

    Orysiak, Joanna; Mazur-Różycka, Joanna; Busko, Krzysztof; Gajewski, Jan; Szczepanska, Beata; Malczewska-Lenczowska, Jadwiga

    2017-02-08

    The aim of this study was to examine the association between ACE and ACTN3 genes, independently or in combination, and muscle strength and power in male and female athletes. The study involved 398 young male (n=266) and female (n=132) athletes representing various sport disciplines (ice hockey, canoeing, swimming, volleyball). All were Caucasians. The following measurements were taken: height of jump and mechanical power in countermovement jump (CMJ) and spike jump (SPJ), and muscle strength of 10 muscle groups (flexors and extensors of the elbow, shoulder, hip, knee and trunk). The ID polymorphism of ACE and the R577X polymorphism of ACTN3 were typed using PCR (polymerase chain reaction) and PCR-RFLP (polymerase chain reaction - restriction fragment length polymorphism), respectively. The genotype distribution of the ACE and ACTN3 genes did not differ significantly between groups of athletes for either sex. There was no association between ACE and ACTN3 genotypes (alone or in combination) and sum of muscle strength, height of jump or mechanical power in both jump tests (CMJ and SPJ) for male and female athletes. These findings do not support an influential role of the ACE and ACTN3 genes in determining power/strength performance of elite athletes.

  7. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates.

    PubMed

    Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2015-12-04

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions.

  8. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Oxidant Activities of Sea Cucumber (Actinopyga lecanora) Hydrolysates

    PubMed Central

    Ghanbari, Raheleh; Zarei, Mohammad; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2015-01-01

    In recent years, food protein-derived hydrolysates have received considerable attention because of their numerous health benefits. Amongst the hydrolysates, those with anti-hypertensive and anti-oxidative activities are receiving special attention as both activities can play significant roles in preventing cardiovascular diseases. The present study investigated the angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities of Actinopyga lecanora (A. lecanora) hydrolysates, which had been prepared by alcalase, papain, bromelain, flavourzyme, pepsin, and trypsin under their optimum conditions. The alcalase hydrolysate showed the highest ACE inhibitory activity (69.8%) after 8 h of hydrolysis while the highest anti-oxidative activities measured by 2,2-diphenyl 1-1-picrylhydrazyl radical scavenging (DPPH) (56.00%) and ferrous ion-chelating (FIC) (59.00%) methods were exhibited after 24 h and 8 h of hydrolysis, respectively. The ACE-inhibitory and anti-oxidative activities displayed dose-dependent trends, and increased with increasing protein hydrolysate concentrations. Moreover, strong positive correlations between angiotensin-I converting enzyme (ACE) inhibitory and anti-oxidative activities were also observed. This study indicates that A. lecanora hydrolysate can be exploited as a source of functional food owing to its anti-oxidant as well as anti-hypertension functions. PMID:26690117

  9. Lysozyme and bilirubin bind to ACE and regulate its conformation and shedding

    PubMed Central

    Danilov, Sergei M.; Lünsdorf, Heinrich; Akinbi, Henry T.; Nesterovitch, Andrew B.; Epshtein, Yuliya; Letsiou, Eleftheria; Kryukova, Olga V.; Piegeler, Tobias; Golukhova, Elena Z.; Schwartz, David E.; Dull, Randal O.; Minshall, Richard D.; Kost, Olga A.; Garcia, Joe G. N.

    2016-01-01

    Angiotensin I-converting enzyme (ACE) hydrolyzes numerous peptides and is a critical participant in blood pressure regulation and vascular remodeling. Elevated tissue ACE levels are associated with increased risk for cardiovascular and respiratory disorders. Blood ACE concentrations are determined by proteolytic cleavage of ACE from the endothelial cell surface, a process that remains incompletely understood. In this study, we identified a novel ACE gene mutation (Arg532Trp substitution in the N domain of somatic ACE) that increases blood ACE activity 7-fold and interrogated the mechanism by which this mutation significantly increases blood ACE levels. We hypothesized that this ACE mutation disrupts the binding site for blood components which may stabilize ACE conformation and diminish ACE shedding. We identified the ACE-binding protein in the blood as lysozyme and also a Low Molecular Weight (LMW) ACE effector, bilirubin, which act in concert to regulate ACE conformation and thereby influence ACE shedding. These results provide mechanistic insight into the elevated blood level of ACE observed in patients on ACE inhibitor therapy and elevated blood lysozyme and ACE levels in sarcoidosis patients. PMID:27734897

  10. Isolation of angiotensin converting enzyme (ACE) inhibiting triterpenes from Schinus molle.

    PubMed

    Olafsson, K; Jaroszewski, J W; Smitt, U W; Nyman, U

    1997-08-01

    Bioactivity-guided fractionation of extracts of Schinus molle leaves, using an in vitro assay, led to the isolation of ACE-inhibitory steroidal triterpenes of the euphane type, identified by means of NMR spectroscopic methods. One of the triterpenes was isolated as an equilibrium mixture of epimeric aldehydes. The triterpenes showed moderate ACE-inhibitory activity (IC(50) about 250 microM).

  11. Tissue and plasma angiotensin converting enzyme and the response to ACE inhibitor drugs.

    PubMed Central

    MacFadyen, R J; Lees, K R; Reid, J L

    1991-01-01

    1. There is a body of circumstantial and direct evidence supporting the existence and functional importance of a tissue based RAS at a variety of sites. 2. The relation between circulatory and tissue based systems is complex. The relative importance of the two in determining haemodynamic effects is unknown. 3. Despite the wide range of ACE inhibitors already available, it remains unclear whether there are genuine differences related to tissue specificity. 4. Pathological states such as chronic cardiac failure need to be explored with regard to the contribution of tissue based ACE activities in generating acute and chronic haemodynamic responses to ACE inhibitors. 5. The role of tissue vs plasma ACE activity may be clarified by study of the relation between drug concentration and haemodynamic effect, provided that the temporal dissociation is examined and linked to circulating and tissue based changes in ACE activity, angiotensin peptides and sympathetic hormones. PMID:1849731

  12. The association between ace gene variation and aerobic capacity in winter endurance disciplines.

    PubMed

    Orysiak, J; Zmijewski, P; Klusiewicz, A; Kaliszewski, P; Malczewska-Lenczowska, J; Gajewski, J; Pokrywka, A

    2013-12-01

    The aim of the study was to examine the possible relationship between I/D polymorphism of ACE gene and selected indices of aerobic capacity among male and female athletes practising winter endurance sports. Sixty-six well-trained athletes (female n = 26, male n = 40), aged 18.4 ± 2.8 years, representing winter endurance sports (cross-country skiing, n = 48; biathlon, n = 8; Nordic combined, n = 10) participated in the study. Genotyping for ACE I/D polymorphism was performed using polymerase chain reaction. Maximal oxygen consumption (VO2max), maximal running velocity (Vmax) and running velocity at anaerobic threshold (VAT4) were determined in an incremental test to volitional exhaustion on a motorized treadmill. The ACE genotype had no significant effect on absolute VO2max, relative VO2max (divided by body mass or fat free body mass), VAT4 or Vmax. No interaction effect of gender x ACE genotype was found for each of the examined aerobic capacity indices. ACE gene variation was not found to be a determinant of aerobic capacity in either female or male Polish, well-trained endurance athletes participating in winter sports.

  13. Inactivation of Transcription Factor Gene ACE2 in the Fungal Pathogen Candida glabrata Results in Hypervirulence

    PubMed Central

    Kamran, Mohammed; Calcagno, Ana-Maria; Findon, Helen; Bignell, Elaine; Jones, Michael D.; Warn, Peter; Hopkins, Philip; Denning, David W.; Butler, Geraldine; Rogers, Thomas; Mühlschlegel, Fritz A.; Haynes, Ken

    2004-01-01

    During an infection, the coordinated orchestration of many factors by the invading organism is required for disease to be initiated and to progress. The elucidation of the processes involved is critical to the development of a clear understanding of host-pathogen interactions. For Candida species, the inactivation of many fungal attributes has been shown to result in attenuation. Here we demonstrate that the Candida glabrata homolog of the Saccharomyces cerevisiae transcription factor gene ACE2 encodes a function that mediates virulence in a novel way. Inactivation of C. glabrata ACE2 does not result in attenuation but, conversely, in a strain that is hypervirulent in a murine model of invasive candidiasis. C. glabrata ace2 null mutants cause systemic infections characterized by fungal escape from the vasculature, tissue penetration, proliferation in vivo, and considerable overstimulation of the proinflammatory arm of the innate immune response. Compared to the case with wild-type fungi, mortality occurs much earlier in mice infected with C. glabrata ace2 cells, and furthermore, 200-fold lower doses are required to induce uniformly fatal infections. These data demonstrate that C. glabrata ACE2 encodes a function that plays a critical role in mediating the host-Candida interaction. It is the first virulence-moderating gene to be described for a Candida species. PMID:15075283

  14. Angiotensin converting enzyme 2 gene expression increased compensatory for left ventricular remodeling in patients with end-stage heart failure.

    PubMed

    Ohtsuki, Masatsugu; Morimoto, Shin-ichiro; Izawa, Hideo; Ismail, Tevfik F; Ishibashi-Ueda, Hatsue; Kato, Yasuchika; Horii, Taiko; Isomura, Tadashi; Suma, Hisayoshi; Nomura, Masanori; Hishida, Hitoshi; Kurahashi, Hiroki; Ozaki, Yukio

    2010-11-19

    It has been reported that angiotensin converting enzyme (ACE) 2, a homologue of ACE, has direct effects on cardiac function. However, the role of ACE2 in the development of human heart failure is not fully understood. We evaluated the expression of the ACE2 gene by means of real-time RT-PCR in myocardium from 14 patients with end-stage heart failure. The amount of ACE2 mRNA positively correlated with left ventricular (LV) end-diastolic diameter (r(2)=0.56, p<0.01) but did not significantly correlate with LV ejection fraction or plasma brain natriuretic peptide levels. In conclusion, our data show that the up-regulation of the ACE2 gene in the LV myocardium of patients with severe heart failure was associated with the degree of LV dilatation and may thereby constitute an important adaptive mechanism to retard the progression of adverse LV remodeling.

  15. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay

    PubMed Central

    2013-01-01

    Background and purpose of the study Angiotensin converting enzyme (ACE) inhibitors plays a critical role in treating hypertension. The purpose of the present investigation was to evaluate ACE inhibition activity of 50 Iranian medicinal plants using an in vitro assay. Methods The ACE activity was evaluated by determining the hydrolysis rate of substrate, hippuryl-L-histidyl-L-leucine (HHL), using reverse phase high performance liquid chromatography (RP-HPLC). Total phenolic content and antioxidant activity were determined by Folin-Ciocalteu colorimetric method and DPPH radical scavenging assay respectively. Results Six extracts revealed > 50% ACE inhibition activity at 330 μg/ml concentration. They were Berberis integerrima Bunge. (Berberidaceae) (88.2 ± 1.7%), Crataegus microphylla C. Koch (Rosaceae) (80.9 ± 1.3%), Nymphaea alba L. (Nymphaeaceae) (66.3 ± 1.2%), Onopordon acanthium L. (Asteraceae) (80.2 ± 2.0%), Quercus infectoria G. Olivier. (Fagaceae) (93.9 ± 2.5%) and Rubus sp. (Rosaceae) (51.3 ± 1.0%). Q. infectoria possessed the highest total phenolic content with 7410 ± 101 mg gallic acid/100 g dry plant. Antioxidant activity of Q. infectoria (IC50 value 1.7 ± 0.03 μg/ml) was more than that of BHT (IC50 value of 10.3 ± 0.15 μg/ml) and Trolox (IC50 value of 3.2 ± 0.06 μg/ml) as the positive controls. Conclusions In this study, we introduced six medicinal plants with ACE inhibition activity. Despite the high ACE inhibition and antioxidant activity of Q. infectoria, due to its tannin content (tannins interfere in ACE activity), another plant, O. acanthium, which also had high ACE inhibition and antioxidant activity, but contained no tannin, could be utilized in further studies for isolation of active compounds. PMID:24359711

  16. Discovery of new angiotensin converting enzyme (ACE) inhibitors from medicinal plants to treat hypertension using an in vitro assay.

    PubMed

    Sharifi, Niusha; Souri, Effat; Ziai, Seyed Ali; Amin, Gholamreza; Amanlou, Massoud

    2013-12-20

    Angiotensin converting enzyme (ACE) inhibitors plays a critical role in treating hypertension. The purpose of the present investigation was to evaluate ACE inhibition activity of 50 Iranian medicinal plants using an in vitro assay. The ACE activity was evaluated by determining the hydrolysis rate of substrate, hippuryl-L-histidyl-L-leucine (HHL), using reverse phase high performance liquid chromatography (RP-HPLC). Total phenolic content and antioxidant activity were determined by Folin-Ciocalteu colorimetric method and DPPH radical scavenging assay respectively. Six extracts revealed > 50% ACE inhibition activity at 330 μg/ml concentration. They were Berberis integerrima Bunge. (Berberidaceae) (88.2 ± 1.7%), Crataegus microphylla C. Koch (Rosaceae) (80.9 ± 1.3%), Nymphaea alba L. (Nymphaeaceae) (66.3 ± 1.2%), Onopordon acanthium L. (Asteraceae) (80.2 ± 2.0%), Quercus infectoria G. Olivier. (Fagaceae) (93.9 ± 2.5%) and Rubus sp. (Rosaceae) (51.3 ± 1.0%). Q. infectoria possessed the highest total phenolic content with 7410 ± 101 mg gallic acid/100 g dry plant. Antioxidant activity of Q. infectoria (IC50 value 1.7 ± 0.03 μg/ml) was more than that of BHT (IC50 value of 10.3 ± 0.15 μg/ml) and Trolox (IC50 value of 3.2 ± 0.06 μg/ml) as the positive controls. In this study, we introduced six medicinal plants with ACE inhibition activity. Despite the high ACE inhibition and antioxidant activity of Q. infectoria, due to its tannin content (tannins interfere in ACE activity), another plant, O. acanthium, which also had high ACE inhibition and antioxidant activity, but contained no tannin, could be utilized in further studies for isolation of active compounds.

  17. High-throughput interpretation of gene structure changes in human and nonhuman resequencing data, using ACE

    USDA-ARS?s Scientific Manuscript database

    We describe a suite of software tools for identifying possible functional changes in gene structure that may result from sequence variants. ACE (“Assessing Changes to Exons”) converts phased genotype calls to a collection of explicit haplotype sequences, maps transcript annotations onto them, detect...

  18. Relationship of Serum Klotho Level With ACE Gene Polymorphism in Stable Kidney Allograft Recipients.

    PubMed

    Zaare Nahandi, Maryam; Ardalan, Mohamad Reza; Banagozar Mohamadi, Ali; Ghorbani Haghjo, Amir; Jabbarpor Bonyadi, Morteza; Mohamadian, Tahere

    2017-03-01

    The kidney is the main source of serum Klotho production. Immunosuppressive agents could affect the kidney in this regard. The effect of the ACE gene polymorphism on Klotho production is a less studied area. This study aimed to assess serum Klotho and ACE gene in a group of stable kidney transplant recipients. In a cross-sectional study, 30 kidney transplant recipients with stable allograft function and 27 healthy young individuals were assessed for their serum Klotho levels. The ACE gene polymorphisms were studied in both groups. Klotho level was higher in kidney transplant recipients than the controls, but the difference was not significant (2.76 ± 2.41 ng/mL versus 2.01 ± 1.41 ng/mL, respectively). In both groups, serum Klotho level was higher in those with the I>I polymorphism, the men, those with higher glomerular filtration rate, and younger individuals, but the differences did not reach a significant level. Higher body mass index was significantly associated with lower serum Klotho level in both groups. Klotho level after kidney transplantation meets the range in healthy individuals, and it is not affected by the ACE gene polymorphism.

  19. Structural determinants for binding to angiotensin converting enzyme 2 (ACE2) and angiotensin receptors 1 and 2

    PubMed Central

    Clayton, Daniel; Hanchapola, Iresha; Thomas, Walter G.; Widdop, Robert E.; Smith, Alexander I.; Perlmutter, Patrick; Aguilar, Marie-Isabel

    2015-01-01

    Angiotensin converting enzyme 2 (ACE2) is a zinc carboxypeptidase involved in the renin–angiotensin system (RAS) and inactivates the potent vasopressive peptide angiotensin II (Ang II) by removing the C-terminal phenylalanine residue to yield Ang1–7. This conversion inactivates the vasoconstrictive action of Ang II and yields a peptide that acts as a vasodilatory molecule at the Mas receptor and potentially other receptors. Given the growing complexity of RAS and level of cross-talk between ligands and their corresponding enzymes and receptors, the design of molecules with selectivity for the major RAS binding partners to control cardiovascular tone is an on-going challenge. In previous studies we used single β-amino acid substitutions to modulate the structure of Ang II and its selectivity for ACE2, AT1R, and angiotensin type 2 (AT2R) receptor. We showed that modification at the C-terminus of Ang II generally resulted in more pronounced changes to secondary structure and ligand binding, and here, we further explore this region for the potential to modulate ligand specificity. In this study, (1) a library of 47 peptides derived from the C-terminal tetrapeptide sequence (-IHPF) of Ang II was synthesized and assessed for ACE2 binding, (2) the terminal group requirements for high affinity ACE2 binding were explored by and N- and C-terminal modification, (3) high affinity ACE2 binding chimeric AngII analogs were then synthesized and assessed, (4) the structure of the full-length Ang II analogs were assessed by circular dichroism, and (5) the Ang II analogs were assessed for AT1R/AT2R selectivity by cell-based assays. Studies on the C-terminus of Ang II demonstrated varied specificity at different residue positions for ACE2 binding and four Ang II chimeric peptides were identified as selective ligands for the AT2 receptor. Overall, these results provide insight into the residue and structural requirements for ACE2 binding and angiotensin receptor selectivity. PMID

  20. The transcription factor HNF1α induces expression of angiotensin-converting enzyme 2 (ACE2) in pancreatic islets from evolutionarily conserved promoter motifs.

    PubMed

    Pedersen, Kim Brint; Chhabra, Kavaljit H; Nguyen, Van K; Xia, Huijing; Lazartigues, Eric

    2013-11-01

    Pancreatic angiotensin-converting enzyme 2 (ACE2) has previously been shown to be critical for maintaining glycemia and β-cell function. Efforts to maintain or increase ACE2 expression in pancreatic β-cells might therefore have therapeutic potential for treating diabetes. In our study, we investigated the transcriptional role of hepatocyte nuclear factor 1α (HNF1α) and hepatocyte nuclear factor 1β (HNF1β) in induction of ACE2 expression in insulin-secreting cells. A deficient allele of HNF1α or HNF1β causes maturity-onset diabetes of the young (MODY) types 3 and 5, respectively, in humans. We found that ACE2 is primarily transcribed from the proximal part of the ACE2 promoter in the pancreas. In the proximal part of the human ACE2 promoter, we further identified three functional HNF1 binding sites, as they have binding affinity for HNF1α and HNF1β and are required for induction of promoter activity by HNF1β in insulinoma cells. These three sites are well-conserved among mammalian species. Both HNF1α and HNF1β induce expression of ACE2 mRNA and lead to elevated levels of ACE2 protein and ACE2 enzymatic activity in insulinoma cells. Furthermore, HNF1α dose-dependently increases ACE2 expression in primary pancreatic islet cells. We conclude that HNF1α can induce the expression of ACE2 in pancreatic islet cells via evolutionarily conserved HNF1 binding sites in the ACE2 promoter. Potential therapeutics aimed at counteracting functional HNF1α depletion in diabetes and MODY3 will thus have ACE2 induction in pancreatic islets as a likely beneficial effect.

  1. Role of ACE I/D gene polymorphisms on the effect of ramipril in inflammatory response and myocardial injury in patients undergoing coronary artery bypass grafts.

    PubMed

    Urhan Küçük, Meral; Sucu, Nehir; Şahan Firat, Seyhan; Aytaçoğlu, Barlas Naim; Vezir, Özden; Bozali, Caner; Canacankatan, Necmiye; Kul, Seval; Tunçtan, Bahar

    2014-12-01

    Angiotensin-converting enzyme (ACE) inhibitors block angiotensin II formation and release bradykinin, which is effective in the regulation of oxidoinflammatory injury. Some reports denote alterations in the effectiveness of ACE inhibitors in association with ACE insertion/deletion (I/D) gene polymorphisms. This study investigates the effects of ramipril on the oxidoinflammatory cytokines (IL-6, IL-8, TNF-alpha) and TnT (myocardial injury marker) and their alteration in association with ACE I/D gene polymorphisms. The study group (n = 51) patients received ramipril before coronary artery bypass grafting (CABG), while patients not receiving ramipril (n = 51) constituted the controls. TNFα, IL-6, and IL-8 were evaluated using ELISA and TnT by electrochemiluminescence methods before the induction of anesthesia (t1), at the 20th minute following cross-clamping (t2), at the end of the operation (t3), and at the 24th hour from the commencement of anesthesia (t4). Genotyping was performed by PCR. Differences between the groups were significant at t4 for the TNFα and at t3 for IL-6 (p < 0.05). The TnT levels increased from t2 onward in the control group and were highest in t3. Changes in t3 and t4 values in both groups according to their t1 values were significant (p < 0.05). However, differences between the groups were insignificant (p > 0.05). The IL-6, IL-8, TNFα, and TnT serum levels had no correlation with the ACE I/D gene polymorphism. Low cytokine and TnT levels in the study group, especially after cross-clamping, may indicate the protective effect of ramipril from oxidoinflammatory injury. This effect did not appear to be associated with the ACE I/D gene polymorphism.

  2. Angiotensin converting enzyme (ACE) inhibitors from Jasminum azoricum and Jasminum grandiflorum.

    PubMed

    Somanadhan, B; Smitt, U W; George, V; Pushpangadan, P; Rajasekharan, S; Duus, J O; Nyman, U; Olsen, C E; Jaroszewski, J W

    1998-04-01

    Bioactivity-guided fractionation of extracts of the aerial parts of Jasminum azoricum var. travancorense, using an in vitro ACE inhibition assay, led to isolation of three oligomeric, iridoid-type compounds, which were named sambacein I-III. Their structures are based on spectroscopic and chemical evidence. Similarly, fractionation of extracts of aerial parts of J. grandiflorum resulted in the isolation of the previously reported ACE inhibitor, oleacein. The IC50 values of purified ACE inhibitors were 26-36 microM. Moreover, 2-(3,4-dihydroxyphenyl)-ethanol, isoquercitrin and ursolic acid were isolated from J. grandiflorum. Sambaceins and oleacein are formed from genuine iridoid glucosides during processing of the plant material. NMR spectroscopy was used to measure the level of the ACE inhibitors in the traditional medicines prepared in Kerala from these Jasminum species.

  3. Relationship Between Angiotensin-converting Enzyme Gene Polymorphism and QT Dispersion in Hemodialysis Patients.

    PubMed

    Toraman, Aysun; Colak, Hulya; Tekce, Hikmet; Cam, Sirri; Kursat, Seyhun

    2017-05-01

    The angiotensin-converting enzyme (ACE) gene insertion or deletion in long-term hemodialysis patients may be associated with corrected QT interval prolongation, leading to fatal arrhythmias. The ACE D allele is known to increase the risk of malignant ventricular arrhythmias and is also associated with increased QT dispersion after myocardial infarction and hypertension. This study aimed to evaluate the relationship between ACE gene polymorphism and QT dispersion in hemodialysis patients. In 70 hemodialysis patients, electrocardiography was performed and QT dispersion was calculated. Corrected QT interval was calculated using Bazett Formula. The ACE gene polymorphism was determined by polymerase chain reaction. The mean age of the patients was 60 ± 12 years. The mean QT dispersion and corrected QT dispersion were 61.71 ± 21.99 and 73.18 ± 25.51, respectively. QT dispersion inversely correlated with serum calcium and potassium levels and positively correlated with ACE gene polymorphism and residual urine. Calcium level was the predictor factor for QT dispersion. The ACE genotype correlated with QT dispersion, corrected QT dispersion, hemoglobin, and residual urine, and inversely correlated with serum potassium. Corrected QT dispersion correlated with ACE gene polymorphism and residual urine. The DD genotype of ACE had significally greater QT dispersion and corrected QT dispersion than the II and ID genotypes. Our study showed that the most important parameter affecting corrected QT dispersion was ACE gene polymorphism on the background of D allelle. Patients carrying this allelle need special attention regarding optimal suppression of renin-angiotensin-aldosteron system activity.

  4. Polymorphisms of ACE2 gene are associated with essential hypertension and antihypertensive effects of Captopril in women.

    PubMed

    Fan, X; Wang, Y; Sun, K; Zhang, W; Yang, X; Wang, S; Zhen, Y; Wang, J; Li, W; Han, Y; Liu, T; Wang, X; Chen, J; Wu, H; Hui, R

    2007-08-01

    ACE2 appears to counterbalance the vasopressor effect of angiotensin I converting enzyme (ACE) in the reninangiotensin system. We hypothesized that ACE2 polymorphisms could confer a high risk of hypertension and have an impact on the antihypertensive response to ACE inhibitors. The hypothesis was tested in two casecontrol studies and a clinical trial of 3,408 untreated hypertensive patients randomized to Atenolol, Hydrochlorothiazide, Captopril, or Nifedipine treatments for 4 weeks. ACE2 rs2106809 T allele was found to confer a 1.6-fold risk for hypertension in women (95% confidence interval (CI), 1.132.06), whereas when combined with the effect of the ACE DD genotype, the risk was 2.34-fold (95% CI, 1.754.85) in two independent samples. The adjusted diastolic blood pressure response to Captopril was 3.3 mm Hg lower in ACE2 T allele carriers than in CC genotype carriers (P=0.019) in women. We conclude that the ACE2 T allele confers a high risk for hypertension and reduced antihypertensive response to ACE inhibitors.

  5. A sex-linked Ace gene, not linked to insensitive acetylcholinesterase-mediated insecticide resistance in Culex pipiens.

    PubMed

    Malcolm, C A; Bourguet, D; Ascolillo, A; Rooker, S J; Garvey, C F; Hall, L M; Pasteur, N; Raymond, M

    1998-05-01

    An acetylcholinesterase (AChE) gene, Ace.x, showing 93% identity of deduced amino acid sequence to Anopheles stephensi Ace has been cloned from a Culex pipiens strain homozygous for insensitive AChE (iAChE) mediated insecticide resistance. DNA sequence of genomic DNA clones identified exons 2-5. RFLP of six clones indicated four possible alleles. Linkage analysis located Ace.x to chromosome I, less than 0.8 centimorgans from the sex locus, whereas the locus conferring resistance was 2.0 centimorgans from plum-eye on chromosome II. Ace.1 coding for AChE1, which is associated with resistance, is therefore autosomal. We propose that Ace.x is the recently postulated Ace.2 coding for the biochemically distinct AChE2, which is not associated with resistance.

  6. Associations of ACE I/D, AGT M235T gene polymorphisms with pregnancy induced hypertension in Chinese population: a meta-analysis.

    PubMed

    Zhu, Ming; Zhang, Jie; Nie, Shaofa; Yan, Weirong

    2012-09-01

    There have been many studies concerning the associations of angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) M235T polymorphisms with pregnancy induced hypertension (PIH) among Chinese populations. However, the results were inconsistent, prompting the necessity of meta-analysis. Studies published in English and Chinese were mainly searched in EMbase, PubMed and CBM up to January 2012. Twenty-three studies with 3,551 subjects for ACE I/D and seven studies with 1,296 subjects for AGT M235T were included. Significant associations were found between ACE I/D and PIH under dominant, recessive and allelic models. A separate analysis confined to preeclampsia suggested that ACE I/D was associated with preeclampsia under recessive model and allelic model, but not dominant model. Stratified analyses were conducted as meta-regression analysis indicated that the sample size of case group was a significant source of heterogeneity, which suggested no significant association between ACE I/D and PIH in the subgroup of more than 100 cases. Associations were found between AGT M235T and PIH under dominant genetic model (OR = 1.59; 95 %CI: 1.04-2.42), recessive genetic model (OR = 1.60; 95 %CI: 1.07-2.40), and allelic model (OR = 1.40; 95 %CI: 1.17-1.68). No publication bias was found in either meta-analysis. The present meta-analysis suggested significant associations between ACE I/D, AGT M235T and PIH in Chinese populations. However, no significant association was found between ACE I/D and PIH in the subgroup of more than 100 cases. Studies with larger sample sizes are necessary to investigate the associations between gene polymorphisms and PIH in Chinese populations.

  7. Contemporary evolution of resistance at the major insecticide target site gene Ace-1 by mutation and copy number variation in the malaria mosquito Anopheles gambiae

    PubMed Central

    Weetman, David; Mitchell, Sara N; Wilding, Craig S; Birks, Daniel P; Yawson, Alexander E; Essandoh, John; Mawejje, Henry D; Djogbenou, Luc S; Steen, Keith; Rippon, Emily J; Clarkson, Christopher S; Field, Stuart G; Rigden, Daniel J; Donnelly, Martin J

    2015-01-01

    Functionally constrained genes are ideal insecticide targets because disruption is often fatal, and resistance mutations are typically costly. Synaptic acetylcholinesterase (AChE) is an essential neurotransmission enzyme targeted by insecticides used increasingly in malaria control. In Anopheles and Culex mosquitoes, a glycine–serine substitution at codon 119 of the Ace-1 gene confers both resistance and fitness costs, especially for 119S/S homozygotes. G119S in Anopheles gambiae from Accra (Ghana) is strongly associated with resistance, and, despite expectations of cost, resistant 119S alleles are increasing significantly in frequency. Sequencing of Accra females detected only a single Ace-1 119S haplotype, whereas 119G diversity was high overall but very low at non-synonymous sites, evidence of strong purifying selection driven by functional constraint. Flanking microsatellites showed reduced diversity, elevated linkage disequilibrium and high differentiation of 119S, relative to 119G homozygotes across up to two megabases of the genome. Yet these signals of selection were inconsistent and sometimes weak tens of kilobases from Ace-1. This unexpected finding is attributable to apparently ubiquitous amplification of 119S alleles as part of a large copy number variant (CNV) far exceeding the size of the Ace-1 gene, whereas 119G alleles were unduplicated. Ace-1 CNV was detectable in archived samples collected when the 119S allele was rare in Ghana. Multicopy amplification of resistant alleles has not been observed previously and is likely to underpin the recent increase in 119S frequency. The large CNV compromised localization of the strong selective sweep around Ace-1, emphasizing the need to integrate CNV analysis into genome scans for selection. PMID:25865270

  8. Role of angiotensin converting enzyme and angiotensinogen gene polymorphisms in angiotensin converting enzyme inhibitor-mediated antiproteinuric action in type 2 diabetic nephropathy patients

    PubMed Central

    Aggarwal, Neerja; Kare, Pawan Kumar; Varshney, Parul; Kalra, Om Prakash; Madhu, Sri Venkata; Banerjee, Basu Dev; Yadav, Anil; Raizada, Alpana; Tripathi, Ashok Kumar

    2017-01-01

    AIM To investigate the role of genetic variants of angiotensin converting enzyme (ACE) and angiotensinogen (AGT) genes in the antiproteinuric efficacy of ACE inhibitor therapy in diabetic nephropathy (DN) patients. METHODS In the present study, 270 type 2 diabetes mellitus patients with nephropathy were enrolled and treated with ACE inhibitor (ramipril) and followed at 6 mo for renal function and albumin excretion by estimating serum creatinine, end stage renal disease, and albumin/creatinine ratio (ACR) in urine. Genotyping of ACE I/D and AGT M235T polymorphisms were performed by using primer specific polymerase chain reaction (PCR) and PCR-RFLP techniques, respectively. RESULTS Forty-eight percent of DN patients (responders) benefited with respect to proteinuria from ACE inhibitor therapy at 6 mo follow-up. A significant reduction in ACR was observed after 6 mo treatment with ACE inhibitor irrespective of whether DN patients were micro-albuminuric (≥ 30 and < 300 mg/g creatinine) or macro-albuminuric (≥ 300 mg/g creatinine) at the time of enrollment. However, macro-albuminuric patients (55%) showed better response to therapy. A reduction in urinary ACR was found independent of genotypes of ACE I/D and AGT M235T polymorphisms although macro-albuminuric patients having TT genotype showed statistically insignificant increased response (72%). CONCLUSION ACE inhibitor therapy reduced urinary ACR by ≥ 30% in 50% of DN patients and the response is independent of ACE I/D and AGT M235T polymorphisms. PMID:28344754

  9. Cloning and functional characterization of the gene encoding the transcription factor Ace1 in the basidiomycete Phanerochaete chrysosporium.

    PubMed

    Polanco, Rubén; Canessa, Paulo; Rivas, Alexis; Larrondo, Luis F; Lobos, Sergio; Vicuña, Rafael

    2006-01-01

    In this report we describe the isolation and characterization of a gene encoding the transcription factor Ace1 (Activation protein of cup 1 Expression) in the white rot fungus Phanerochaete chrysosporium. Pc-ace1 encodes a predicted protein of 633 amino acids containing the copper-fist DNA binding domain typically found in fungal transcription factors such as Ace1, Mac1 and Haa1 from Saccharomyces cerevisiae. The Pc-ace1 gene is localized in Scaffold 5, between coordinates 220841 and 222983. A S. cerevisiae ace1 null mutant strain unable to grow in high-copper medium was fully complemented by transformation with the cDNA of Pc-ace1. Moreover, Northern blot hybridization studies indicated that Pc-ace1 cDNA restores copper inducibility of the yeast cup 1 gene, which encodes the metal-binding protein metallothionein implicated in copper resistance. To our knowledge, this is first report describing an Ace1 transcription factor in basidiomycetes.

  10. Association of ACE Gene I/D polymorphism with migraine in Kashmiri population

    PubMed Central

    Wani, Irfan Yousuf; Sheikh, Saleem; Shah, Zafar Amin; Pandith, Arshid A.; Wani, Mushtaq; Asimi, Ravouf; Wani, Maqbool; Sheikh, Shahnawaz; Mehraj, Iqra

    2016-01-01

    Introduction: Migraine is a complex, recurrent headache disorder that is one of the most common complaints in neurology practice. The role of various genes in its pathogenesis is being studied. We did this study to see whether an association exists between ACE gene I/D polymorphism and migraine in our region. Materials and Methods: The study included 100 patients diagnosed with migraine and 121 healthy controls. The study subject were age and gender matched. The analysis was based on Polymerase Chain Reaction (PCR) and included following steps: DNA extraction from blood, PCR and Restriction Fragment Length Polymorphism (RFLP). Results: Out of 100 cases, 69 were females and 31 were males. Fifty-seven were having migraine without aura and 43 had migraine with aura. 45 of the cases had II polymorphism, 40 had ID polymorphism and 15 had DD polymorphism in ACE gene. Conclusion: We were not able to find a statistically significant association between ACE gene I/D polymorphism with migraine. The reason for difference in results between our study and other studies could be because of different ethnicity in study populations. So a continuous research is needed in this regard in order to find the genes and different polymorphism that increase the susceptibility of Kashmiri population to migraine. PMID:27011636

  11. Enzyme evolution beyond gene duplication

    PubMed Central

    Noda-García, Lianet; Barona-Gómez, Francisco

    2013-01-01

    Understanding the evolution of enzyme function after gene duplication has been a major goal of molecular biologists, biochemists and evolutionary biologists alike, for almost half a century. In contrast, the impact that horizontal gene transfer (HGT) has had on the evolution of enzyme specialization and the assembly of metabolic networks has just started to being investigated. Traditionally, evolutionary studies of enzymes have been limited to either the function of enzymes in vitro, or to sequence variability at the population level, where in almost all cases the starting conceptual framework embraces gene duplication as the mechanism responsible for the appearance of genetic redundancy. Very recently, we merged comparative phylogenomics, detection of selection signals, enzyme kinetics, X-ray crystallography and computational molecular dynamics, to characterize the sub-functionalization process of an amino acid biosynthetic enzyme prompted by an episode of HGT in bacteria. Some of the evolutionary implications of these functional studies, including a proposed model of enzyme specialization independent of gene duplication, are developed in this commentary. PMID:24251070

  12. COC use, ACE/AGT gene polymorphisms, and risk of stroke.

    PubMed

    Li, Ying; Chen, Feng; Zhou, Lifeng; Coulter, David; Chen, Cheng; Sun, Zhiming; Chen, Jianfeng; Pan, Hongxin; Wu, Yulin; Zhou, Jian; Ba, Lei; Zhao, Jinna; Shen, Hongbing

    2010-05-01

    To clarify the effects of the association between combined oral contraceptives (COC) use and ACE/AGT gene on stroke risk, and to undertake a preliminarily study of the molecular mechanism of the association between COC exposure and predisposing genes of hypertension on the increased risk of stroke. This study was a multi-center case-control study based on the population of 25 towns in the surveillance regions of Jiangsu province, China. (i) The univariate analysis of the frequency of the DD genotype of ACE insert/delete (I/D) polymorphism between the cases and controls indicated its significant association with the stroke (P<0.01), especially for hemorrhagic stroke (P<0.01). (ii) Women with COC exposure and ACE I/D genotype had an increased risk for all strokes [adjusted odds ratio 5.63; 95% confidence interval (CI), 2.20, 15.68], and an increased risk for hemorrhagic stroke (adjusted odds ratio 31.53; 95% CI, 3.54, 281.14) after adjustment for education and occupation. (iii) Multivariate analyses showed that hypertension was the most important risk factor for hemorrhagic stroke and ischemic stroke. COC use was a significant risk factor for hemorrhagic stroke. The combined effects of COC use, for 15 years and above, and ACE I/D polymorphism increased the risk of all strokes by more than eight times, and the risk of hemorrhagic stroke by more than 15 times. Hypertension was a most important risk factor for stroke incidence. The D allele of ACE I/D polymorphism may be a potential risk allele for stroke. COC users carried the ID+DD genotype that may further increase the risk of stroke, especially for hemorrhagic stroke.

  13. Association between the Angiotensin-Converting Enzyme (ACE) Genetic Polymorphism and Diabetic Retinopathy-A Meta-Analysis Comprising 10,168 Subjects.

    PubMed

    Luo, Shasha; Shi, Chao; Wang, Furu; Wu, Zhifeng

    2016-11-15

    Aims-to address the inconclusive findings of the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods-we conducted a meta-analysis on 4252 DR cases and 5916 controls from 40 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the overall and stratification effect sizes on ACE I/D polymorphism on the risk of DR. Results-we found a significant association between the ACE I/D polymorphism and the risk of DR for all genetic model (ID vs. II: OR = 1.14, 95% CI: 1.00-1.30; DD vs. II: OR = 1.38, 95% CI: 1.11-1.71; Allele contrast: OR = 1.17, 95% CI: 1.05-1.30; recessive model: OR = 1.24, 95% CI: 1.02-1.51 and dominant model: OR = 1.21, 95% CI: 1.06-1.38, respectively). In stratified analysis by ethnicity and DM type, we further found that the Asian group with T2DM showed a significant association for all genetic models (ID vs. II: OR = 1.14, 95% CI: 1.01-1.30; DD vs. II: OR = 1.54, 95% CI: 1.14-2.08; Allele contrast: OR = 1.26, 95% CI: 1.09-1.47; recessive model: OR = 1.42, 95% CI: 1.07-1.88 and dominant model: OR = 1.26, 95% CI: 1.07-1.49, respectively). Conclusion-our study suggested that the ACE I/D polymorphism may contribute to DR development, especially in the Asian group with type 2 diabetes mellitus (T2DM). Prospective and more genome-wide association studies (GWAS) are needed to clarify the real role of the ACE gene in determining susceptibility to DR.

  14. Association between the Angiotensin-Converting Enzyme (ACE) Genetic Polymorphism and Diabetic Retinopathy—A Meta-Analysis Comprising 10,168 Subjects

    PubMed Central

    Luo, Shasha; Shi, Chao; Wang, Furu; Wu, Zhifeng

    2016-01-01

    Aims—to address the inconclusive findings of the association of angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism on risk of diabetic retinopathy (DR), a meta-analysis was conducted. Methods—we conducted a meta-analysis on 4252 DR cases and 5916 controls from 40 published studies by searching electronic databases and reference lists of relevant articles. A random-effects or fixed-effects model was used to estimate the overall and stratification effect sizes on ACE I/D polymorphism on the risk of DR. Results—we found a significant association between the ACE I/D polymorphism and the risk of DR for all genetic model (ID vs. II: OR = 1.14, 95% CI: 1.00–1.30; DD vs. II: OR = 1.38, 95% CI: 1.11–1.71; Allele contrast: OR = 1.17, 95% CI: 1.05–1.30; recessive model: OR = 1.24, 95% CI: 1.02–1.51 and dominant model: OR = 1.21, 95% CI: 1.06–1.38, respectively). In stratified analysis by ethnicity and DM type, we further found that the Asian group with T2DM showed a significant association for all genetic models (ID vs. II: OR = 1.14, 95% CI: 1.01–1.30; DD vs. II: OR = 1.54, 95% CI: 1.14–2.08; Allele contrast: OR = 1.26, 95% CI: 1.09–1.47; recessive model: OR = 1.42, 95% CI: 1.07–1.88 and dominant model: OR = 1.26, 95% CI: 1.07–1.49, respectively). Conclusion—our study suggested that the ACE I/D polymorphism may contribute to DR development, especially in the Asian group with type 2 diabetes mellitus (T2DM). Prospective and more genome-wide association studies (GWAS) are needed to clarify the real role of the ACE gene in determining susceptibility to DR. PMID:27854313

  15. A novel acetylcholinesterase gene in mosquitoes codes for the insecticide target and is non-homologous to the ace gene in Drosophila.

    PubMed Central

    Weill, Mylène; Fort, Philippe; Berthomieu, Arnaud; Dubois, Marie Pierre; Pasteur, Nicole; Raymond, Michel

    2002-01-01

    Acetylcholinesterase (AChE) is the target of two major insecticide families, organophosphates (OPs) and carbamates. AChE insensitivity is a frequent resistance mechanism in insects and responsible mutations in the ace gene were identified in two Diptera, Drosophila melanogaster and Musca domestica. However, for other insects, the ace gene cloned by homology with Drosophila does not code for the insensitive AChE in resistant individuals, indicating the existence of a second ace locus. We identified two AChE loci in the genome of Anopheles gambiae, one (ace-1) being a new locus and the other (ace-2) being homologous to the gene previously described in Drosophila. The gene ace-1 has no obvious homologue in the Drosophila genome and was found in 15 mosquito species investigated. In An. gambiae, ace-1 and ace-2 display 53% similarity at the amino acid level and an overall phylogeny indicates that they probably diverged before the differentiation of insects. Thus, both genes are likely to be present in the majority of insects and the absence of ace-1 in Drosophila is probably due to a secondary loss. In one mosquito (Culex pipiens), ace-1 was found to be tightly linked with insecticide resistance and probably encodes the AChE OP target. These results have important implications for the design of new insecticides, as the target AChE is thus encoded by distinct genes in different insect groups, even within the Diptera: ace-2 in at least the Drosophilidae and Muscidae and ace-1 in at least the Culicidae. Evolutionary scenarios leading to such a peculiar situation are discussed. PMID:12396499

  16. Identification of positive and negative transcriptional regulatory elements of the rabbit angiotensin-converting enzyme gene.

    PubMed Central

    Goraya, T Y; Kessler, S P; Kumar, R S; Douglas, J; Sen, G C

    1994-01-01

    The two tissue-specific mRNAs encoding the isozymes of rabbit angiotensin-converting enzyme (ACE) are generated from the same gene by alternative choice of two transcription initiation sites 5.7 kb apart. In the current study, we have characterized the regulatory sites controlling the transcription of the larger pulmonary isozyme mRNA. For this purpose, reporter genes driven by varying lengths of upstream region of the ACE gene were transfected into ACE-producing cells. Our results demonstrated that the transcription of this gene is primarily driven by positive elements within the first 274 bp DNA upstream of the transcription initiation site. The reporter gene driven by this region was expressed in two ACE-producing cells but not in two ACE-non-producing cells thereby establishing its tissue specificity. Our experiments also revealed the existence of a strong negative element located between -692 and -610 positions. This element suppressed the expression of the reporter gene in a dose-dependent and position and orientation-independent fashion thus suggesting that it is a true silencer element. It could also repress the expression of a reporter gene driven by the heterologous strong promoter of the beta-actin gene. The repressing effects of the negative element could be partially overcome by cotransfecting the isolated negative element along with the reporter gene containing the negative element. This result was possibly due to the functional removal of a limiting trans-acting factor which binds to this element. Electrophoretic mobility shift assays revealed that the negative element can form several complexes with proteins present in the nuclear extract of an ACE-producing cell line. At least part of the negative element is strongly conserved in the upstream regions of the human and mouse ACE genes. Images PMID:8165133

  17. Epistatic effects of ACE I/D and AGT gene variants on left ventricular mass in hypertensive patients: the HyperGEN study.

    PubMed

    Lynch, A I; Tang, W; Shi, G; Devereux, R B; Eckfeldt, J H; Arnett, D K

    2012-02-01

    Identifying predictors of left ventricular hypertrophy has been an active study topic because of its association with cardiovascular morbidity and mortality. We examined the epistatic effect (gene-gene interaction) of two genes (angiotensin-converting enzyme (ACE) insertion/deletion (I/D); angiotensinogen (AGT) -6G-A, M235T, -20A-C) in the renin-angiotensin system on left ventricular mass (LVM) among hypertensive participants in the Hypertension Genetic Epidemiology Network study. Included were 2156 participants aged 20-87 years (60% women, 63% African American). We employed mixed linear regression models to assess main effects of four genetic variants on echocardigraphically determined LVM (indexed for height), and ACE-by-AGT epistatic effects. There was evidence that AGT -6G-A was associated with LVM among white participants: adjusted mean LVM (gm(-2.7)) increased with 'G' allele copy number ('AA':41.2, 'AG':42.3, 'GG':44.0; P=0.03). There was also evidence of an ACE I/D-by-AGT -20A-C epistatic effect among white participants (interaction P=0.03): among ACE 'DD' participants, AGT -20A-C 'C' allele carriers had lower mean LVM than 'AA' homozygotes ('DD/CC':39.2, 'DD/AC':39.9, 'DD/AA':43.9), with no similar significant effect among ACE 'I' allele carriers ('ID/CC':47.2, 'ID/AC':43.4, 'ID/AA':42.6; 'II/CC': NA, 'II/AC':41.3, 'II/AA':43.1). These findings indicate that renin-angiotensin system variants in at least two genes may interact to modulate LVM.

  18. ACE Gene I/D Polymorphism and Obesity in 1,574 Patients with Type 2 Diabetes Mellitus

    PubMed Central

    Wang, Min; Huang, Yan-Mei; Wang, Ying-Hui; Chen, Yin-Ling; Geng, Li-Jun

    2016-01-01

    Association between ACE gene I/D polymorphism and the risk of overweight/obesity remains controversial. We investigated the possible relationship between ACE gene I/D polymorphism and obesity in Chinese type 2 diabetes mellitus (T2DM) patients. In this study, obesity was defined as a body mass index (BMI) value ≥ 25 kg/m2 and subjects were classified into 4 groups (lean, normal, overweight, and obese). PCR (polymerase chain reaction) was used to detect the ACE gene I/D polymorphism in T2DM patients. Metabolic measurements including blood glucose, lipid profile, and blood pressure were obtained. Frequencies of the ACE genotypes (DD, ID, and II) were not significant among the 4 groups of BMI-defined patients (P = 0.679) while ACE II carriers showed higher systolic blood pressure (SBP) and pulse pressure (PP) (all P < 0.050). Hyperglycemia, hypertension, and dyslipidemia in these T2DM patients were found to be significantly associated with BMI. In conclusion, the relationship of ACE gene I/D polymorphism with obesity is insignificant in Chinese patients with T2DM. SBP and PP might be higher in the ACE II carriers than in the DD and ID carriers. PMID:28115791

  19. An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3

    PubMed Central

    Edwards, Todd L.; Pericak-Vance, Margaret; Gilbert, Johnny; Haines, Jonathan L.; Martin, Eden; Ritchie, Marylyn D.

    2009-01-01

    Alzheimer’s disease (AD) is the most common form of progressive dementia in the elderly. It is a neurodegenerative disorder characterized by the neuropathologic findings of intracellular neurofibrillary tangles and extracellular amyloid plaques that accumulate in vulnerable brain regions. AD etiology has been studied by many groups, but since the discovery of the APOE ε4 allele, no further genes have been mapped conclusively to the late-onset form of the disease. In this study, we examined genetic association with late-onset Alzheimer’s susceptibility in 738 Caucasian families with 4704 individuals and an independent case-control dataset with 296 unrelated cases and 566 unrelated controls exploring 11 candidate genes with 47 SNPs common to both samples. In addition to tests for main effects and haplotype analyses, the Multifactor Dimensionality Reduction Pedigree Disequilibrium Test (MDR-PDT) was used to search for single-locus effects as well as 2-locus and 3-locus gene-gene interactions associated with AD in the family data. We observed significant haplotype effects in ACE in both family and case-control samples using standard and cladistic haplotype models. ACE was also part of significant 2-locus and 3-locus MDR-PDT joint effects models with Alpha-2-Macroglobulin (A2M), which mediates the clearance of Aβ, and Leucine-Rich Repeat Transmembrane 3 (LRRTM3), a nested gene in Alpha-3 Catenin (CTNNA3) which binds Presenilin 1. This result did not replicate in the case-control sample, and may not be a true positive. These genes are related to amyloid beta clearance; thus this constellation of effects might constitute an axis of susceptibility for late-onset AD. The consistent ACE haplotype result between independent data sets of families and unrelated cases and controls is strong evidence in favor of ACE as a susceptibility locus for AD, and replicates results from several other studies in a very large sample. PMID:19105203

  20. Evaluation of Association of ADRA2A rs553668 and ACE I/D Gene Polymorphisms with Obesity Traits in the Setapak Population, Malaysia

    PubMed Central

    Shunmugam, Vicneswari; Say, Yee-How

    2016-01-01

    Background α-adrenergic receptor 2A (ADRA2A) and angiotensin-converting enzyme (ACE) genes have been variably associated with obesity and its related phenotypes in different populations worldwide. Objectives This cross-sectional study aims to investigate the association of adrenergic receptor α2A (ADRA2A) rs553668 and angiotensin-converting enzyme (ACE) I/D single nucleotide polymorphisms (SNPs) with obesity traits (body mass index-BMI; waist-hip ratio-WHR; total body fat percentage - TBF) in a Malaysian population. Materials and Methods Demographic and clinical variables were initially collected from 230 subjects via convenience sampling among residents and workers in Setapak, Malaysia, but in the end only 214 multi-ethnic Malaysians (99 males; 45 Malays, 116 ethnic Chinese, and 53 ethnic Indians) were available for statistical analysis. Genotyping was performed by polymerase chain reaction using DNA extracted from mouthwash samples. Results The overall minor allele frequencies (MAFs) for ADRA2A rs553668 and ACE I/D were 0.55 and 0.56, respectively. Allele distribution of ACE I/D was significantly associated with ethnicity and WHR class. Logistic regression analysis showed that subjects with the ACE II genotype and I allele were, respectively, 2.15 and 1.55 times more likely to be centrally obese, but when adjusted for age and ethnicity, this association was abolished. Covariate analysis controlling for age, gender, and ethnicity also showed similar results, where subjects carrying the II genotype or I allele did not have significantly higher WHR. Combinatory genotype and allele analysis for ADRA2A rs553668 and ACE I/D showed that subjects with both ADRA2A rs553668 GG and ACE I/D II genotypes had significant lowest WHR compared to other genotype combinations. Conclusions The ACE II genotype might be a protective factor against central adiposity risk among the Malaysian population when in combination with the ADRA2A rs553668 GG genotype. PMID:27186390

  1. Association between angiotensin-converting enzyme gene polymorphisms and regression of left ventricular hypertrophy in patients treated with angiotensin-converting enzyme inhibitors.

    PubMed

    Kohno, M; Yokokawa, K; Minami, M; Kano, H; Yasunari, K; Hanehira, T; Yoshikawa, J

    1999-05-01

    An insertion/deletion (ID) polymorphism of the angiotensin-converting enzyme (ACE) gene is associated with left ventricular hypertrophy. The present study examined polymorphisms of the ACE gene in patients with essential hypertension and left ventricular hypertrophy who were participants in a long-term trial of therapy with an ACE inhibitor. ACE inhibitor therapy was administered for >2 years to 54 patients with hypertension who had moderate or severe left ventricular hypertrophy. Cardiac dimensions were monitored by echocardiography before the initiation of therapy and after 1 and 2 years of treatment. Serum ACE activity and plasma concentrations of brain natriuretic peptide, a marker for left ventricular hypertrophy, were also monitored. Eighteen patients had the II genotype for the angiotensin-converting enzyme gene, 19 had the ID genotype, and 17 had the DD genotype. Baseline (mean +/- SD) serum ACE activity was significantly greater (P <0.05) in the DD (18 +/- 7 IU/L) group than in the II (7 +/- 4 IU/L) or ID (12 +/- 6 IU/L) groups. ACE inhibitor therapy was effective in controlling blood pressure, and it reduced posterior and septal wall thickness, left ventricular mass index, and plasma brain natriuretic peptide concentration in all three groups. Despite similar blood pressure reductions, after 2 years, mean (+/- SD) regression in posterior wall thickness was significantly less (P <0.05) in the DD group (-9% +/- 5%) than in the ID (-21% +/- 7%) and II (-21% +/- 9%) groups. Similar results were seen for the reductions in brain natriuretic peptide levels. The magnitudes of regression of septal wall thickness and left ventricular mass index during therapy were less in the DD group than the II group (P <0.05). Hypertensive patients with the DD genotype are less likely to have regression of left ventricular hypertrophy when treated with ACE inhibitors than are patients with other ACE genotypes.

  2. Inhibitors of angiotensin-converting enzyme modulate mitosis and gene expression in pancreatic cancer cells

    SciTech Connect

    Reddy, M.K.; Baskaran, K.; Molteni, A.

    1995-12-01

    The angiotensin-converting enzyme (ACE) inhibitor captopril inhibits mitosis in several cell types that contain ACE and renin activity. In the present study, we evaluated the effect of the ACE inhibitors captopril and CGS 13945 (10{sup {minus}8} to 10{sup {minus}2}M) on proliferation and gene expression in hamster pancreatic duct carcinoma cells in culture. These cells lack renin and ACE activity. Both ACE inhibitors produced a dose-dependent reduction in tumor cell proliferation within 24 hr. Captopril at a concentration of 0.36 mM and CGS 13945 at 150 {mu}M decreased cellular growth rate to approximately half that of the control. Neither drug influenced the viability or the cell cycle distribution of the tumor cells. Slot blot analysis of mRNA for four genes, proliferation associated cell nuclear antigen (PCNA), K-ras, protein kinase C-{Beta} (PKC-{Beta}) and carbonic anhydrase II (CA II) was performed. Both ACE inhibitors increased K-ras expression by a factor of 2, and had no effect on CA II mRNA levels. Captopril also lowered PCNA by 40% and CGS 13945 lowered PKC-{Beta} gene expression to 30% of the control level. The data demonstrate that ACE inhibitors exhibit antimitotic activity and differential gene modulation in hamster pancreatic duct carcinoma cells. The absence of renin and ACE activity in these cells suggests that the antimitotic action of captopril and CGS 13945 is independent of renin-angiotensin regulation. The growth inhibition may occur through downregulation of growth-related gene expression. 27 refs., 5 figs.

  3. ACE polymorphism and use of ACE inhibitors: effects on memory performance.

    PubMed

    Schuch, Jaqueline B; Constantin, Pamela C; da Silva, Vanessa K; Korb, Camila; Bamberg, Daiani P; da Rocha, Tatiane J; Fiegenbaum, Marilu; de Oliveira, Alcyr; Tisser, Luciana A; de Andrade, Fabiana M

    2014-06-01

    Memory is an important cognition function, being fundamental to the development and independence of individuals. Our aim was to investigate the influence apolipoprotein E (APOE) and angiotensin I-converting enzyme (ACE) polymorphism and ACE inhibitors use, besides their interaction on memory performance of healthy subjects over 50 years. The sample consisted of 205 subjects assessed for five types of episodic memory, using Wechsler Memory Scale-Revised (WMS-R), who answered a questionnaire about drug use and were assessed for the ACE insertion/deletion polymorphism and APOE polymorphism. We found no influence of the APOE gene. The use of ACE inhibitors beneficially influenced learning ability scores (p = 0.02). Besides, I allele carriers of ACE polymorphism showed higher verbal memory scores compared with homozygous DD. Also, we observed an interaction influencing learning ability between the ACE polymorphism and the use of inhibitors, the beneficial influence of the I allele was present only in individuals who make use of ACE inhibitors. We conclude that the ACE gene has influence on memory performance, and that this influence is modulated by ACE inhibitors use.

  4. ACE and ACE2 in kidney disease

    PubMed Central

    Mizuiri, Sonoo; Ohashi, Yasushi

    2015-01-01

    Renin angiotensin system (RAS) activation has a significant influence on renal disease progression. The classical angiotensin-converting enzyme (ACE)-angiotensin II (Ang II)-Ang II type 1 (AT1) axis is considered to control the effects of RAS activation on renal disease. However, since its discovery in 2000 ACE2 has also been demonstrated to have a significant impact on the RAS. The synthesis and catabolism of Ang II are regulated via a complex series of interactions, which involve ACE and ACE2. In the kidneys, ACE2 is expressed in the proximal tubules and less strongly in the glomeruli. The synthesis of inactive Ang 1-9 from Ang I and the catabolism of Ang II to produce Ang 1-7 are the main functions of ACE2. Ang 1-7 reduces vasoconstriction, water retention, salt intake, cell proliferation, and reactive oxygen stress, and also has a renoprotective effect. Thus, in the non-classical RAS the ACE2-Ang 1-7-Mas axis counteracts the ACE-Ang II-AT1 axis. This review examines recent human and animal studies about renal ACE and ACE2. PMID:25664248

  5. [Polymorphism of genes of the renin-angiotensin system ACE, AT1R, and AT2R in patients with pulmonary tuberculosis].

    PubMed

    Ogarkov, O B; Sin'kov, V V; Medvedeva, T V; Gutnikova, M Iu; Nekipelov, O M; Raevskaia, L Iu; Kuptsevich, N Iu; Kostiunin, K Iu; Skvortsova, R G

    2008-01-01

    The goal of this work was to verify the hypothesis about the possible role of some genes of the renin-angiotensin system in the innate immunity to tuberculosis. The insertion/deletion polymorphism (I/D) of the gene of the angiotensin-converting enzyme (ACE) is known to have an effect on the concentration of the angiotensin II in human body and also an indirect effect on various branches of metabolism. On the one hand, people with homozygote deletion of the ACE gene (DD genotype) are vulnerable to adiposity, arterial hypertension, hypercholesterolemia, and a number of other pathological conditions. On the other hand, it was shown that hypocholesterolemia is the general phenomenon for the patients with pulmonary tuberculosis (Perez-Guzman C. et al., Chest (2005)). In this work, we studied the I/D polymorphism of the gene ACE (genotypes DD, ID, and II), single nucleotide polymorphism (SNP) of the gene AT1R (1166 A/C), and SNP in 3123 positions of the gene AT2R (3123 A/C) in 200 patients with tuberculosis, 202 patients with essential hypertension, and 208 apparently healthy subjects. A group of patients with essential hypertension was used as a contrast group. According to the hypothesis stated above, the excess in the number of patients with the DD genotype (ACE) should be statistically significant in the group of patients with hypertension as compared to the group of patients with tuberculosis (chi2 = 9.64; chi2 = 0.0019; OR = 2.0; CI 1.2-3.3). There was a trend toward an increase in the rate of the DD genotype in the group of patients with tuberculosis relative to healthy subjects. Similar trend was observed in healthy subjects relative to the group of patients with hypertension. However, this difference was found to be statistically insignificant. The genotypes and allelotypes were compared in the group of patients with tuberculosis versus both the two control groups (healthy subjects and patients with hypertension). The significant difference from control was

  6. [ACE and AGTR1 genes polymorphisms in left ventricular hypertrophy pathogenesis in humans].

    PubMed

    Makeeva, O A; Puzyrev, K V; Pavliukova, E N; Koshel'skaia, O A; Golubenko, M V; Efimova, E V; Kucher, A N; Tsimbaliuk, I V; Karpov, R S; Puzyrev, V P

    2004-01-01

    The role of A2350G polymorphism in exon 17 of the ACE gene and A1166C - in 3'-UTR of the AGTR1 in the pathogenesis of left ventricular hypertrophy was studied in patients with essential hypertension (EH) and arterial hypertension combined with diabetes mellitus type 2 (AH + DM2). Patients with EH and AH + DM2 did not differ from the control sample of healthy individuals by allele or genotype frequencies. However, an association of both polymorphisms with LVH was detected in EH patients. The frequency of 1166C allele was higher in patients with LVH (33.6% vs 20.7% without LVH). A1166C polymorphism determined the magnitude of left ventricular mass index (LVMI) in EH patients as well (p = 0.007). 2350G allele frequency of the ACE gene was in 1.5, and GG genotype--in 3.5-fold higher in EH patients with LVH, as compared without LVH. LVMI was significantly higher in patients with GG genotype as compared with heterozygotes and AA homozygotes (p = 0.002). Thus the presence of 1166C allele of AGTR1 and 2350G allele of ACE can be considered as predisposing factors for LVH development in EH. In contrast, association of studied polymorphisms with presence or LVH degree was not detected in patients with arterial hypertension combined with DM2. This may indicate another structure of genetic component of predisposition to LVH in different causes.

  7. The Angiotensin Converting Enzyme 2 (ACE2), Gut Microbiota, and Cardiovascular Health.

    PubMed

    Andrade, João Marcus Oliveira; de Farias Lelis, Deborah; Mafra, Valeria; Cota, Junio

    2017-07-28

    The renin-angiotensin system (RAS) is an important enzymatic system responsible for the regulation of biological functions, such as the arterial pressure, hydroelectrolytic control and vascular vasodilatation/vasoconstriction. The RAS component ACE2 acts as a mediator in vasoprotection, and it is highly expressed in the kidney, heart, and testis. Recently, the association between the ACE2 and gut microbiota has been discussed. It is shown that the ACE2/Ang-(1-7) axis modulates the immune response, influencing the microbiota composition, and thus being one of the causes for some diseases physiophatologies, such as diarrhea and intestinal inflammatory disease. The association between RAS and gut microbiota seems to have a strong influence on the genesis of cardiovascular diseases, through direct mechanisms, such as nerve stimulation, or indirect, on metabolic parameters, such as weight, adiposity and lipid profile. In this perspective, this review presents the recent evidence regarding the relationship between RAS, gut microbiota and cardiovascular diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  8. Ascorbic Acid Protects against Hypertension through Downregulation of ACE1 Gene Expression Mediated by Histone Deacetylation in Prenatal Inflammation-Induced Offspring

    PubMed Central

    Wang, Jing; Yin, Na; Deng, Youcai; Wei, Yanling; Huang, Yinhu; Pu, Xiaoyun; Li, Li; Zheng, Yingru; Guo, Jianxin; Yu, Jianhua; Li, Xiaohui; Yi, Ping

    2016-01-01

    Hypertension is a major risk factor for cardiovascular and cerebrovascular disease. Prenatal exposure to lipopolysaccharide (LPS) leads to hypertension in a rat offspring. However, the mechanism is still unclear. This study unraveled epigenetic mechanism for this and explored the protective effects of ascorbic acid against hypertension on prenatal inflammation-induced offspring. Prenatal LPS exposure resulted in an increase of intrarenal oxidative stress and enhanced angiotensin-converting enzyme 1 (ACE1) gene expression at the mRNA and protein levels in 6- and 12-week-old offspring, correlating with the augmentation of histone H3 acetylation (H3AC) on the ACE1 promoter. However, the prenatal ascorbic acid treatment decreased the LPS-induced expression of ACE1, protected against intrarenal oxidative stress, and reversed the altered histone modification on the ACE1 promoter, showing the protective effect in offspring of prenatal LPS stimulation. Our study demonstrates that ascorbic acid is able to prevent hypertension in offspring from prenatal inflammation exposure. Thus, ascorbic acid can be a new approach towards the prevention of fetal programming hypertension. PMID:27995995

  9. Copper and the ACE1 Regulatory Protein Reversibly Induce Yeast Metallothionein Gene Transcription in a Mouse Extract

    NASA Astrophysics Data System (ADS)

    Cizewski Culotta, Valeria; Hsu, Tsao; Hu, Stella; Furst, Peter; Hamer, Dean

    1989-11-01

    We describe a cell-free system in which the transcription of the yeast metallothionein gene is inducible by the addition of metal ions plus a specific regulatory protein. Efficient transcription requires the complete yeast ACE1 metalloregulatory protein, including both its DNA-binding and transactivation domains; a mouse nuclear extract providing RNA polymerase and general transcription factors; a template containing the ACE1 binding site; and Cu(I). Because the binding of ACE1 to DNA is dependent on Cu, it is possible to inhibit transcription by the use of Cu-complexing agents such as CN-. We have used this specific inhibition to show that the ACE1 regulatory protein is required for the maintenance as well as the formation of a functional preinitiation complex. The ability to reversibly induce yeast metallothionein gene transcription in vitro provides a powerful system for determining the molecular mechanism of a simple eukaryotic regulatory circuit.

  10. Association of angiotensin-converting enzyme and angiotensin II type I receptor gene polymorphisms with extreme obesity in Polish individuals.

    PubMed

    Pacholczyk, Marta; Ferenc, Tomasz; Kowalski, Jan; Adamczyk, Przemysław; Chojnowski, Jacek; Ponikowska, Irena

    2013-08-01

    There is strong evidence for the presence of a functional renin-angiotensin system in human adipose tissue. The aim of our study was to investigate the association of polymorphic variants of angiotensin-converting enzyme gene (ACE I/D) and angiotensin II type I receptor gene (AGTR1 A1166C) with extreme obesity and obesity-associated type 2 diabetes mellitus (T2DM) and to examine their combined effect on extremely obese patients. Overall, no significant associations were detected between ACE and AGTR1 gene polymorphisms and extreme obesity. However, extremely obese patients with T2DM showed an increased frequency of ACE II genotype compared with controls (p<0.05) and with non-diabetic extremely obese patients (p<0.01). The results suggest that II genotype of ACE was a significant contributor to extreme obesity in AA homozygotes of AGTR1 gene, regardless of the presence of T2DM. Moreover, the analysis of genetic polymorphisms demonstrated that ACE II and AGTR1 AC genotypes were most frequently observed in patients with extreme obesity and T2DM. On the basis of our results, we suggest that ACE II homozygosity may be a significant predictor of extreme obesity and T2DM and that the interaction between ACE and AGTR1 genes may be considered a predisposing factor for extreme obesity and extreme obesity-associated T2DM development.

  11. The binding of metal ions and angiotensin converting enzyme (ACE) inhibitor by 13C NMR

    NASA Astrophysics Data System (ADS)

    Sakamoto, Yohko; Sakamoto, Yuko; Ishii, Tomoko; Ohmoto, Taichi

    1991-06-01

    Enalaprilat (MK-422, 1- [ N- [1 (S)-carboxy-3-phenylpropyl]- L-alanyl]- L-proline (1)) and Lisinopril (MK521, N- N- [ (s)-l-carboxy-3- phenylpropyl]- L-lysyl- L-proline, (2)) exhibit the capacity to act as a chelate, unidentate or bridge towards metal ions in aqueous solution, as determined by 13C NMR. By adding metal ions, in the series of Zn 2+, Ni 2+, Pb 2+, Pd 2+ and Cd 2+, the active site of the ACE inhibitor was well defined. MK-521 was more influenced by nuclei that were distant from the active site than MK-422.

  12. Genetic variants of ACE (Insertion/Deletion) and AGT (M268T) genes in patients with diabetes and nephropathy.

    PubMed

    Shaikh, Rozeena; Shahid, Syed M; Mansoor, Qaisar; Ismail, Muhammad; Azhar, Abid

    2014-06-01

    Diabetes mellitus (DM) has been a growing epidemic worldwide and poses a major socio-economic challenge. The leading cause of DM death is nephropathy due to end-stage renal disease (ESRD). This study aims to identify the possible association of I/D variants of the ACE gene and M268T (rs699) of the AGT gene of renin-angiotensin-aldosterone system (RAAS). Study subjects include 115 patients with DM, 110 with diabetic nephropathy (DN) and 110 controls. Fasting blood samples were collected for biochemical analyses and PCR amplification of specific regions of the ACE and AGT genes using primers. The distribution of ACE (I/D) II 28.8%, ID 35.6% and DD 35.6% while in DN II 24.5%, ID 41% and DD 34.5%. The AGT (M268T) genotypes were distributed in DM as TT 30.4%, MT 66.9% and MM 2.6% while in DN subjects TT 56.4%, MT 42.7% and MM 0.9%. Significant differences were observed in the DD genotype and D allele of the ACE gene and the TT genotype and T allele of AGT genes between diabetic patients with and without nephropathy. The study may conclude that the D allele polymorphism in the ACE gene and the T allele polymorphism in AGT gene may be considered as genetic risk factors for the development of nephropathy in diabetes. © The Author(s) 2014.

  13. Association of ACE, FABP2 and GST genes polymorphism with essential hypertension risk among a North Indian population.

    PubMed

    Abbas, Shania; Raza, Syed Tasleem; Chandra, Anu; Rizvi, Saliha; Ahmed, Faisal; Eba, Ale; Mahdi, Farzana

    2015-01-01

    Hypertension has a multi-factorial background based on genetic and environmental interactive factors. ACE, FABP2 and GST genes have been suggested to be involved in the development of hypertension. However, the results have been inconsistent. The present study was carried out to investigate the association of ACE (rs4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism with essential HTN cases and controls. This study includes 138 essential hypertension (HTN) patients and 116 age-, sex- and ethnicity-matched control subjects. GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphisms were evaluated by multiplex PCR, ACE (rs4646994) gene polymorphisms by PCR and FABP2 (rs1799883) gene polymorphisms by PCR-RFLP method. Significant differences were obtained in the frequencies of ACE DD, II genotype (p = 0.006, 0.003), GSTT1 null, GSTM1 positive genotype (p = 0.048, 0.010) and FABP2 Ala54/Ala54 genotype (p = 0.049) between essential HTN cases and controls. It is concluded that ACE (rs 4646994), FABP2 (rs1799883) and GST (GSTM1 null or positive genotype and GSTT1 null or positive genotype) genes polymorphism are associated with HTN. Further investigation with a larger sample size may be required to validate this study.

  14. RETRACTED: Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression.

    PubMed

    Yang, Chun-Hua; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Chun-Hua Yang and Tian-Biao Zhou Association of the ACE I/D gene polymorphism with sepsis susceptibility and sepsis progression Journal of Renin-Angiotensin-Aldosterone System 1470320314568521, first published on February 3, 2015 doi: 10.1177/1470320314568521 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 Tian-Biao Zhou, Xue-Feng Guo, Zongpei

  15. Separation and Characterization of Angiotensin I Converting Enzyme (ACE) Inhibitory Peptides from Saurida elongata Proteins Hydrolysate by IMAC-Ni(2).

    PubMed

    Sun, Lixia; Wu, Shanguang; Zhou, Liqin; Wang, Feng; Lan, Xiongdiao; Sun, Jianhua; Tong, Zhangfa; Liao, Dankui

    2017-02-15

    Lizard fish protein hydrolysates (LFPH) were prepared from Lizard fish (Saurida elongata) proteins possessing powerful angiotensin I converting enzyme (ACE) inhibitory activity and the fraction (LFPH-I) with high ACE inhibitory activity was obtained through ultrafiltration. The active Fraction (F2) was isolated from LFPH-I using immobilized metal affinity chromatography (IMAC-Ni(2+)). Analysis of amino acid levels revealed that F2 eluted from IMAC was enriched in Met, His, Tyr, Pro, Ile, and Leu compared to the crude peptide LFPH-I. F2 with the high ACE inhibitory activity (IC50 of 0.116 mg·mL(-1)) was further separated by a reverse-phase column to yield a novel ACE inhibitory peptide with IC50 value of 52 μM. The ACE inhibitory peptide was identified as Arg-Tyr-Arg-Pro, RYRP. The present study demonstrated that IMAC may be a useful tool for the separation of ACE inhibitory peptides from protein hydrolysate.

  16. Separation and Characterization of Angiotensin I Converting Enzyme (ACE) Inhibitory Peptides from Saurida elongata Proteins Hydrolysate by IMAC-Ni2+

    PubMed Central

    Sun, Lixia; Wu, Shanguang; Zhou, Liqin; Wang, Feng; Lan, Xiongdiao; Sun, Jianhua; Tong, Zhangfa; Liao, Dankui

    2017-01-01

    Lizard fish protein hydrolysates (LFPH) were prepared from Lizard fish (Saurida elongata) proteins possessing powerful angiotensin I converting enzyme (ACE) inhibitory activity and the fraction (LFPH-I) with high ACE inhibitory activity was obtained through ultrafiltration. The active Fraction (F2) was isolated from LFPH-I using immobilized metal affinity chromatography (IMAC-Ni2+). Analysis of amino acid levels revealed that F2 eluted from IMAC was enriched in Met, His, Tyr, Pro, Ile, and Leu compared to the crude peptide LFPH-I. F2 with the high ACE inhibitory activity (IC50 of 0.116 mg·mL−1) was further separated by a reverse-phase column to yield a novel ACE inhibitory peptide with IC50 value of 52 μM. The ACE inhibitory peptide was identified as Arg-Tyr-Arg-Pro, RYRP. The present study demonstrated that IMAC may be a useful tool for the separation of ACE inhibitory peptides from protein hydrolysate. PMID:28212269

  17. Individualized Angiotensin-Converting Enzyme (ACE)-Inhibitor Therapy in Stable Coronary Artery Disease Based on Clinical and Pharmacogenetic Determinants: The PERindopril GENEtic (PERGENE) Risk Model.

    PubMed

    Oemrawsingh, Rohit M; Akkerhuis, K Martijn; Van Vark, Laura C; Redekop, W Ken; Rudez, Goran; Remme, Willem J; Bertrand, Michel E; Fox, Kim M; Ferrari, Roberto; Danser, A H Jan; de Maat, Moniek; Simoons, Maarten L; Brugts, Jasper J; Boersma, Eric

    2016-03-28

    Patients with stable coronary artery disease (CAD) constitute a heterogeneous group in which the treatment benefits by angiotensin-converting enzyme (ACE)-inhibitor therapy vary between individuals. Our objective was to integrate clinical and pharmacogenetic determinants in an ultimate combined risk prediction model. Clinical, genetic, and outcomes data were used from 8726 stable CAD patients participating in the EUROPA/PERGENE trial of perindopril versus placebo. Multivariable analysis of phenotype data resulted in a clinical risk score (range, 0-21 points). Three single-nucleotide polymorphisms (rs275651 and rs5182 in the angiotensin-II type I-receptor gene and rs12050217 in the bradykinin type I-receptor gene) were used to construct a pharmacogenetic risk score (PGXscore; range, 0-6 points). Seven hundred eighty-five patients (9.0%) experienced the primary endpoint of cardiovascular mortality, nonfatal myocardial infarction or resuscitated cardiac arrest, during 4.2 years of follow-up. Absolute risk reductions ranged from 1.2% to 7.5% in the 73.5% of patients with PGXscore of 0 to 2. As a consequence, estimated annual numbers needed to treat ranged from as low as 29 (clinical risk score ≥10 and PGXscore of 0) to 521 (clinical risk score ≤6 and PGXscore of 2). Furthermore, our data suggest that long-term perindopril prescription in patients with a PGXscore of 0 to 2 is cost-effective. Both baseline clinical phenotype, as well as genotype determine the efficacy of widely prescribed ACE inhibition in stable CAD. Integration of clinical and pharmacogenetic determinants in a combined risk prediction model demonstrated a very wide range of gradients of absolute treatment benefit. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  18. Inhibition of angiotensin converting enzyme (ACE) by flavonoids isolated from Ailanthus excelsa (Roxb) (Simaroubaceae).

    PubMed

    Loizzo, Monica Rosa; Said, Ataa; Tundis, Rosa; Rashed, Khaled; Statti, Giancarlo Antonio; Hufner, Antje; Menichini, Francesco

    2007-01-01

    In our screening program for antihypertensive properties of plants, the leaves of Ailanthus excelsa (Roxb), a plant used in Egyptian traditional medicine, were analysed. Chromatographic separation of A. excelsa MeOH extract yielded six flavonoids for the first time from this species, namely apigenin, luteolin, kaempferol-3-O-alpha-arabinopyranoside, kaempferol-3-O-beta-galactopyranoside, quercetin-3-O-alpha-arabinopyranoside and luteolin-7-O-beta-glucopyranoside. The in vitro hypotensive activities of the MeOH extract and the isolated compounds were elucidated. All the flavonoids tested exhibited ACE inhibitory activity, in particular the most active compound was kaempferol-3-O-beta-galactopyranoside with an IC(50) value of 260 microm.

  19. Effect of ID ACE gene polymorphism on dietary composition and obesity-related anthropometric parameters in the Czech adult population.

    PubMed

    Bienertova-Vasku, Julie; Bienert, Petr; Sablikova, Lenka; Slovackova, Lenka; Forejt, Martin; Piskackova, Zlata; Kucerova, Lenka; Heczkova, Katerina; Brazdova, Zuzana; Vasku, Anna

    2009-09-01

    The aim of this study was to investigate the possible associations between insertion/deletion (ID) polymorphism in angiotensin-converting enzyme (ACE) (dbSNP rs 4646994) with the food intake and body composition in the Czech non-obese, obese and extremely obese populations. A total of 453 various-weighted individuals were enrolled in the study and were according to their BMI assigned into following subgroups, such as obese (30 /=40) and non-obese (20 < BMI < 30) subjects. Both the obese cases and the non-obese controls underwent the identical subset of standardized examinations (BMI, % body fat, waist-to-hip ratio, skin fold thickness, native dietary composition examined by 7-day food records, etc.). No significant case-control differences in genotype distributions or allelic frequencies were observed. There were no differences in genotype frequencies between males and females either. The prevalence of obesity was significantly higher among subjects with the II genotype (42 %) when compared with those with DD (36%) and those with ID (37%) genotypes (P = 0.04). When compared with carbohydrate intake in the whole studied cohort, the odds ratios of carrying the DD allele in the morbidly obese cohort were 0.84 (95% CI 0.34, 2.10, P = 0.17), 0.27 (0.07, 0.98, P = 0.02), and 4.25 (1.44, 12.51, P = 0.005) in those individuals consuming <210, 210-260, and >260 g of carbohydrates/day, respectively. Based on our findings, the ID ACE polymorphism could represent a gene modulator of carbohydrate intake in morbidly obese Czech population; the strong significant effect of DD genotype was observed in the phenotypes of extreme obesity with the highest carbohydrate intake.

  20. In vitro inhibitory activities of selected Australian medicinal plant extracts against protein glycation, angiotensin converting enzyme (ACE) and digestive enzymes linked to type II diabetes.

    PubMed

    Deo, Permal; Hewawasam, Erandi; Karakoulakis, Aris; Claudie, David J; Nelson, Robert; Simpson, Bradley S; Smith, Nicholas M; Semple, Susan J

    2016-11-04

    There is a need to develop potential new therapies for the management of diabetes and hypertension. Australian medicinal plants collected from the Kuuku I'yu (Northern Kaanju) homelands, Cape York Peninsula, Queensland, Australia were investigated to determine their therapeutic potential. Extracts were tested for inhibition of protein glycation and key enzymes relevant to the management of hyperglycaemia and hypertension. The inhibitory activities were further correlated with the antioxidant activities. Extracts of five selected plant species were investigated: Petalostigma pubescens, Petalostigma banksii, Memecylon pauciflorum, Millettia pinnata and Grewia mesomischa. Enzyme inhibitory activity of the plant extracts was assessed against α-amylase, α-glucosidase and angiotensin converting enzyme (ACE). Antiglycation activity was determined using glucose-induced protein glycation models and formation of protein-bound fluorescent advanced glycation endproducts (AGEs). Antioxidant activity was determined by measuring the scavenging effect of plant extracts against 1, 1-diphenyl-2-picryl hydrazyl (DPPH) and using the ferric reducing anti-oxidant potential assay (FRAP). Total phenolic and flavonoid contents were also determined. Extracts of the leaves of Petalostigma banksii and P. pubescens showed the strongest inhibition of α-amylase with IC50 values of 166.50 ± 5.50 μg/mL and 160.20 ± 27.92 μg/mL, respectively. The P. pubescens leaf extract was also the strongest inhibitor of α-glucosidase with an IC50 of 167.83 ± 23.82 μg/mL. Testing for the antiglycation potential of the extracts, measured as inhibition of formation of protein-bound fluorescent AGEs, showed that P. banksii root and fruit extracts had IC50 values of 34.49 ± 4.31 μg/mL and 47.72 ± 1.65 μg/mL, respectively, which were significantly lower (p < 0.05) than other extracts. The inhibitory effect on α-amylase, α-glucosidase and the antiglycation potential of the

  1. High-throughput genotyping of single-nucleotide polymorphisms in ace-1 gene of mosquitoes using MALDI-TOF mass spectrometry.

    PubMed

    Mao, Yun; Tan, Feng; Yan, Shuai-Guo; Wu, Guo-Xing; Qiao, Chuan-Ling; Zhang, Wen-Xue; Cui, Feng

    2013-04-01

    Acetylcholinesterase (AChE) plays a vital role in the nervous system of insects and other animal species and serves as the target for many chemical agents such as organophosphate and carbamate insecticides. The mosquito, Culex pipiens complex, a vector of human disease, has evolved to be resistant to insecticides by a limited number of amino acid substitutions in AChE1, which is encoded by the ace-1 gene. The aims of this study are to identify single nucleotide polymorphism (SNP) sites in the ace-1 gene of the C. pipiens complex and explore an economical high-throughput method to differentiate the genotypes of these sites in mosquitoes collected in the field. We identified 22 SNP sites in exon regions of the ace-1 gene. Four of them led to non-synonymous mutations, that is, Y163C, G247S, C677S and T682A. We used matrix-assisted laser desorption ionization - time-of-flight mass spectrometry for genotyping at these four sites and another site F416V, which was relevant to insecticide resistance, in 150 mosquitoes collected from 15 field populations. We were able to synchronize analysis of the five SNP sites in each well of a 384-well plate for each individual mosquito, thus decreasing the cost to one-fifth of the routine analysis. Heterozygous genotypes at Y163C and G247S sites were observed in one mosquito. The possible influence of the five SNP sites on the activity or function of the enzyme is discussed based on the predicted tertiary structure of the enzyme.

  2. Angiotensin-converting enzyme 2 (ACE2) proteins of different bat species confer variable susceptibility to SARS-CoV entry.

    PubMed

    Hou, Yuxuan; Peng, Cheng; Yu, Meng; Li, Yan; Han, Zhenggang; Li, Fang; Wang, Lin-Fa; Shi, Zhengli

    2010-10-01

    The discovery of SARS-like coronavirus in bats suggests that bats could be the natural reservoir of SARS-CoV. However, previous studies indicated the angiotensin-converting enzyme 2 (ACE2) protein, a known SARS-CoV receptor, from a horseshoe bat was unable to act as a functional receptor for SARS-CoV. Here, we extended our previous study to ACE2 molecules from seven additional bat species and tested their interactions with human SARS-CoV spike protein using both HIV-based pseudotype and live SARS-CoV infection assays. The results show that ACE2s of Myotis daubentoni and Rhinolophus sinicus support viral entry mediated by the SARS-CoV S protein, albeit with different efficiency in comparison to that of the human ACE2. Further, the alteration of several key residues either decreased or enhanced bat ACE2 receptor efficiency, as predicted from a structural modeling study of the different bat ACE2 molecules. These data suggest that M. daubentoni and R. sinicus are likely to be susceptible to SARS-CoV and may be candidates as the natural host of the SARS-CoV progenitor viruses. Furthermore, our current study also demonstrates that the genetic diversity of ACE2 among bats is greater than that observed among known SARS-CoV susceptible mammals, highlighting the possibility that there are many more uncharacterized bat species that can act as a reservoir of SARS-CoV or its progenitor viruses. This calls for continuation and expansion of field surveillance studies among different bat populations to eventually identify the true natural reservoir of SARS-CoV.

  3. CYP6 P450 enzymes and ACE-1 duplication produce extreme and multiple insecticide resistance in the malaria mosquito Anopheles gambiae.

    PubMed

    Edi, Constant V; Djogbénou, Luc; Jenkins, Adam M; Regna, Kimberly; Muskavitch, Marc A T; Poupardin, Rodolphe; Jones, Christopher M; Essandoh, John; Kétoh, Guillaume K; Paine, Mark J I; Koudou, Benjamin G; Donnelly, Martin J; Ranson, Hilary; Weetman, David

    2014-03-01

    Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with

  4. CYP6 P450 Enzymes and ACE-1 Duplication Produce Extreme and Multiple Insecticide Resistance in the Malaria Mosquito Anopheles gambiae

    PubMed Central

    Jenkins, Adam M.; Regna, Kimberly; Muskavitch, Marc A. T.; Poupardin, Rodolphe; Jones, Christopher M.; Essandoh, John; Kétoh, Guillaume K.; Paine, Mark J. I.; Koudou, Benjamin G.; Donnelly, Martin J.; Ranson, Hilary; Weetman, David

    2014-01-01

    Malaria control relies heavily on pyrethroid insecticides, to which susceptibility is declining in Anopheles mosquitoes. To combat pyrethroid resistance, application of alternative insecticides is advocated for indoor residual spraying (IRS), and carbamates are increasingly important. Emergence of a very strong carbamate resistance phenotype in Anopheles gambiae from Tiassalé, Côte d'Ivoire, West Africa, is therefore a potentially major operational challenge, particularly because these malaria vectors now exhibit resistance to multiple insecticide classes. We investigated the genetic basis of resistance to the most commonly-applied carbamate, bendiocarb, in An. gambiae from Tiassalé. Geographically-replicated whole genome microarray experiments identified elevated P450 enzyme expression as associated with bendiocarb resistance, most notably genes from the CYP6 subfamily. P450s were further implicated in resistance phenotypes by induction of significantly elevated mortality to bendiocarb by the synergist piperonyl butoxide (PBO), which also enhanced the action of pyrethroids and an organophosphate. CYP6P3 and especially CYP6M2 produced bendiocarb resistance via transgenic expression in Drosophila in addition to pyrethroid resistance for both genes, and DDT resistance for CYP6M2 expression. CYP6M2 can thus cause resistance to three distinct classes of insecticide although the biochemical mechanism for carbamates is unclear because, in contrast to CYP6P3, recombinant CYP6M2 did not metabolise bendiocarb in vitro. Strongly bendiocarb resistant mosquitoes also displayed elevated expression of the acetylcholinesterase ACE-1 gene, arising at least in part from gene duplication, which confers a survival advantage to carriers of additional copies of resistant ACE-1 G119S alleles. Our results are alarming for vector-based malaria control. Extreme carbamate resistance in Tiassalé An. gambiae results from coupling of over-expressed target site allelic variants with

  5. ACE inhibition modifies exercise-induced pro-angiogenic and mitochondrial gene transcript expression.

    PubMed

    van Ginkel, S; Ruoss, S; Valdivieso, P; Degens, H; Waldron, S; de Haan, A; Flück, M

    2016-10-01

    Skeletal muscle responds to endurance exercise with an improvement of biochemical pathways that support substrate supply and oxygen-dependent metabolism. This is reflected by enhanced expression of associated factors after exercise and is specifically modulated by tissue perfusion and oxygenation. We hypothesized that transcript expression of pro-angiogenic factors (VEGF, tenascin-C, Angpt1, Angpt1R) and oxygen metabolism (COX4I1, COX4I2, HIF-1α) in human muscle after an endurance stimulus depends on vasoconstriction, and would be modulated through angiotensin-converting enzyme inhibition by intake of lisinopril. Fourteen non-specifically trained, male Caucasians subjects, carried out a single bout of standardized one-legged bicycle exercise. Seven of the participants consumed lisinopril in the 3 days before exercise. Biopsies were collected pre- and 3 h post-exercise from the m. vastus lateralis. COX4I1 (P = 0.03), COX4I2 (P = 0.04) mRNA and HIF-1α (P = 0.05) mRNA and protein levels (P = 0.01) showed an exercise-induced increase in the group not consuming the ACE inhibitor. Conversely, there was a specific exercise-induced increase in VEGF transcript (P = 0.04) and protein levels (P = 0.03) and a trend for increased tenascin-c transcript levels (P = 0.09) for subjects consuming lisinopril. The observations indicate that exercise-induced expression of transcripts involved in angiogenesis and mitochondrial energy metabolism are to some extent regulated via a hypoxia-related ACE-dependent mechanism.

  6. Coexistence of ACE (I/D) and PAI-1 (4G/5G) gene variants in recurrent miscarriage in Polish population.

    PubMed

    Kurzawińska, Grażyna; Barlik, Magdalena; Drews, Krzysztof; Różycka, Agata; Seremak-Mrozikiewicz, Agnieszka; Ożarowski, Marcin; Klejewski, Andrzej; Czerny, Bogusław; Wolski, Hubert

    2016-01-01

    Recurrent miscarriage (RM) is one of the most common obstetric complications. Numerous studies have suggested that genetic variants leading to an impaired balance between coagulation and fibrinolysis may contribute to elevated risk of pregnancy loss. The aim of the study was to investigate a possible association between angiotensin-converting enzyme (ACE, rs1799752) I/D and plasminogen activator inhibitor type 1 (PAI-1, rs1799768) 4G/5G polymorphisms with RM among Polish women. DNA was extracted from peripheral blood samples of 152 women with a history of ≥ 2 consecutive pregnancy losses before 22 weeks of gestation, and 180 healthy controls with at least 1 live birth at term and no history of pregnancy loss. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were used to identify the polymorphisms. No statistically significant differences were found in genotype and allele frequencies of the studied polymorphisms. The most relevant difference between the study group and controls was found for the ID genotype distribution of the ACE gene (52.6 vs. 46.7%, OR = 1.27, p = 0.28). The analysis of genotype coexistence revealed a higher incidence of the combination of the ACE II and the PAI-1 4G/4G genotypes in the control group (10.0 vs.5.9% in control group; p = 0.17). The obtained results suggest no apparent association between the ACE I/D, PAI-1 4G/5G polymorphisms and increased RM susceptibility in the analyzed Polish population.

  7. Endothelial Nitric Oxide Synthase and Angiotensin Converting Enzyme Gene Polymorphisms in Migraine Patients

    PubMed Central

    SİPAHİ, Tammam; GÜLDİKEN, Babürhan; KABAYEL, Levent; PALABIYIK, Orkide; ÖZKAN, Hülya; KILIÇ, Tülay Okman; SÜT, Necdet; TURGUT, Nilda

    2013-01-01

    Introduction In this study, we investigated the association of migraine with the Variable Number of Tandem Repeats (VNTR), repeated as 27 base pair, gene polymorphism in intron 4 of the endothelial nitric oxide synthase (eNOS) and the insertion/deletion of angiotensin converting enzyme (ACE) gene polymorphisms. Methods One hundred and five migraine and ninety seven healthy female control subjects were enrolled in the study. The patients were subdivided as migraine with aura and without aura, and the frequency and severity of migraine headaches were recorded. The eNOS VNTR (eNOS 4 a/b) and ACE insertion/deletion gene polymorphisms (ACE I/D) were assessed by polymerase chain reactions. Result The allele and genotype frequencies of eNOS 4 a/b gene polymorphism showed no difference between the migraine and control groups. The genotypic distribution of the ACE I/D gene polymorphism in the migraine group significantly differed from that in the control group. The DD and ID genotype increased the risk of migraine as much as 2.571 (95% CI-1.138–5.811) and 4.453 (95% CI-2.006–9.883) compared to the II genotype. The same increased risk sustained for both genotypes in the migraine with aura subgroup, but only the ID genotype remained as the risk factor in the migraine without aura subgroup (OR-3.750, 95% CI-1.493–9.420). No association of gene polymorphisms with migraine frequency and severity was observed. Conclusion Our findings support the relationship between migraine and the ACE I/D gene polymorphism. However, no association was found between migraine and the eNOS 4 a/b gene polymorphism.

  8. A multilocus candidate approach identifies ACE and HIF1A as susceptibility genes for cellulite.

    PubMed

    Emanuele, E; Bertona, M; Geroldi, D

    2010-08-01

    Cellulite is a common complex cosmetic problem for many post-adolescent women characterised by relief alterations of the skin surface, which give the skin an orange-peel appearance. Although genetic factors have been suggested to play a role in the development of cellulite, the genetic background of this condition remains unclear. We therefore conducted a multi-locus genetic study examining the potential associations of candidate gene variants in oestrogen receptors, endothelial function/adipose tissue hypoxia, lipid metabolism, extracellular matrix homeostasis, inflammation and adipose tissue biology, with the risk of cellulite. Using a case-control study of 200 lean women with cellulite and 200 age- and BMI-matched controls (grade 0 according to Nurnberger-Muller scale), we examined the association of cellulite with 25 polymorphisms in 15 candidate genes. Two of the 25 polymorphisms were significantly associated with cellulite at the P < 0.01 level. After allowance for age, body mass index, the prevalence of contraceptive use and smoking in logistic regression analysis, the multivariable-adjusted odds ratios for cellulite were 1.19 (95% CI: 1.10-1.51; P < 0.01) for ACE rs1799752 and 0.61 (95% CI: 0.45-0.88, P < 0.01) for HIF1A rs11549465. This study, which demonstrates an independent role of ACE and HIF1A in predisposing to cellulite, may provide novel information on the pathophysiology of this common cosmetic problem, and offer a topic for research for novel beautification interventions.

  9. Angiotensin converting enzyme (ACE) inhibitory and antihypertensive activities of protein hydrolysate from meat of Kacang goat (Capra aegagrus hircus).

    PubMed

    Mirdhayati, Irdha; Hermanianto, Joko; Wijaya, Christofora H; Sajuthi, Dondin; Arihara, Keizo

    2016-08-01

    The meat of Kacang goat has potential for production of a protein hydrolysate. Functional ingredients from protein hydrolysate of Kacang goat meat were determined by the consistency of angiotensin-converting enzyme (ACE) inhibitory activity and antihypertensive effect. This study examined the potency of Kacang goat protein hydrolysate in ACE inhibition and antihypertensive activity. Protein hydrolysates of Kacang goat meat were prepared using sequential digestion of endo-proteinase and protease complex at several concentrations and hydrolysis times. The highest ACE inhibitory activity resulted from a hydrolysate that was digested for 4 h with 5 g kg(-1) of both enzymes. An ACE inhibitory peptide was purified and a novel peptide found with a sequence of Phe-Gln-Pro-Ser (IC50 value of 27.0 µmol L(-1) ). Both protein hydrolysates and a synthesised peptide (Phe-Gln-Pro-Ser) demonstrated potent antihypertensive activities in spontaneously hypertensive rats. Protein hydrolysate of Kacang goat meat produced by sequential digestion with endo-proteinase and protease complex has great potential as a functional ingredient, particularly as an antihypertensive agent. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

  10. Screening of inhibitors of angiotensin-converting enzyme (ACE) employing high performance liquid chromatography-electrospray ionization triple quadrupole mass spectrometry (HPLC-ESI-QqQ-MS).

    PubMed

    Musharraf, Syed Ghulam; Bhatti, Muhammad Salman; Choudhary, Muhammad Iqbal; Rahman, Atta-Ur

    2017-04-01

    Angiotensin-converting enzyme (ACE) plays a key role in regulating blood pressure in the body by converting the angiotensin I (AI) into angiotensin II (AII). Angiotensin II is a potent vaso-active peptide that causes arterioles to constrict, resulting in increased blood pressure. A rapid and sensitive method for the identification of inhibitors of ACE was developed, and optimized employing HPLC-ESI-QqQ-MS. In this assay, angiotensin I substrate was converted into the product angiotensin II with the catalytic action of ACE. A calibration curve for depleting concentration of angiotensin I was developed and linearity of R(2)=0.999 with a remarkably low concentration of substrate range 20-200nM. The limit of detection and quantification of angiotensin I was found to be 1.93 and 5.84nM, respectively. The enzymatic reaction was optimized for incubation time, concentration, and volume of enzyme and substrate. All reactions were performed at 37°C at pH7.5 with standard incubation time of 20min. Two standard inhibitors, Captopril and Lisinopril, were checked through the newly developed method for their inhibitory potential, and their IC50 values were found to be 3.969 and 0.852μM, respectively. Reproducibility and precision analysis of different experiments showed <9.9% RSD. The developed method can be used for the identification of new ACE inhibitors.

  11. Association of angiotensin-converting enzyme, CYP46A1 genes polymorphism with senile cataract

    PubMed Central

    Raza, Syed Tasleem; Abbas, Shania; Chandra, Anu; Singh, Luxmi; Rizvi, Saliha; Mahdi, Farzana

    2017-01-01

    Background: Senile cataract is the most common type of cataract characterized by gradual progressive thickening of the lens of the eye. Previously, many studies investigated the association between genetic polymorphism and senile cataract. Angiotensin-converting enzyme (ACE) I/D polymorphism is the potential risk factor for many eye-related diseases such as retinopathy and glaucoma. CYP46A1 enzyme converts cholesterol to 24S-hydroxycholesterol; human lens' membranes contain the highest cholesterol content. Defects in enzymes of cholesterol metabolism can be associated with cataracts. Hence, the present study was carried out to investigate the association of ACE and CYP46A1 genes polymorphism with senile cataract cases and controls. Materials and Methods: ACE (rs 4646994) and CYP46A1 (rs 754203) genes polymorphism in cases and controls were evaluated by polymerase chain reaction and restriction fragment length polymorphism. Results: This study included 103 senile cataract cases (55 were males and 48 were females) and 102 controls (53 were males and 49 were females). Mean age of cases in this study was 52.02 ± 12.11 years while in control group 53.74 ± 11.87 years. Frequencies of ACE ID, DD, and II genotypes in senile cataract cases were 64.07%, 4.85%, and 31.06% and controls were 61.76%, 26.47%, and 11.76%, respectively. The CYP46A1 gene CT, CC, and TT genotype frequencies were 48.54%, 8.73%, and 42.71% in senile cataract cases and 28.43%, 3.92%, and 67.64% in healthy controls, respectively. ACE DD and II genotypes (P < 0.001,P = 0.0008) and CYP46A1 CT and TT genotypes (P = 0.003,P = 0.0003) were significantly associated with senile cataract cases compared to the controls. Conclusion: Findings of this study suggest that ACE and CYP46A1 genes polymorphism may be a predictive marker for early identification of population at risk of senile cataract. This potential role of ACE and CYP46A1 genes polymorphism as a marker of susceptibility to senile cataract needs

  12. Heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease.

    PubMed

    Wang, Wang; Patel, Vaibhav B; Parajuli, Nirmal; Fan, Dong; Basu, Ratnadeep; Wang, Zuocheng; Ramprasath, Tharmarajan; Kassiri, Zamaneh; Penninger, Josef M; Oudit, Gavin Y

    2014-08-01

    Angiotensin-converting enzyme 2 (ACE2) metabolizes Ang II into Ang 1-7 thereby negatively regulating the renin-angiotensin system. However, heart disease in humans and in animal models is associated with only a partial loss of ACE2. ACE2 is an X-linked gene; and as such, we tested the clinical relevance of a partial loss of ACE2 by using female ACE2(+/+) (wildtype) and ACE2(+/-) (heterozygote) mice. Pressure overload in ACE2(+/-) mice resulted in greater LV dilation and worsening systolic and diastolic dysfunction. These changes were associated with increased myocardial fibrosis, hypertrophy, and upregulation of pathological gene expression. In response to Ang II infusion, there was increased NADPH oxidase activity and myocardial fibrosis resulting in the worsening of Ang II-induced diastolic dysfunction with a preserved systolic function. Ang II-mediated cellular effects in cultured adult ACE2(+/-) cardiomyocytes and cardiofibroblasts were exacerbated. Ang II-mediated pathological signaling worsened in ACE2(+/-) hearts characterized by an increase in the phosphorylation of ERK1/2 and JNK1/2 and STAT-3 pathways. The ACE2(+/-) mice showed an exacerbated pressor response with increased vascular fibrosis and stiffness. Vascular superoxide and nitrotyrosine levels were increased in ACE2(+/-) vessels consistent with increased vascular oxidative stress. These changes occurred with increased renal fibrosis and superoxide production. Partial heterozygote loss of ACE2 is sufficient to increase the susceptibility to heart disease secondary to pressure overload and Ang II infusion. Heart disease in humans with idiopathic dilated cardiomyopathy is associated with a partial loss of ACE2. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to pressure overload-induced heart disease. Heterozygote female ACE2 mutant mice showed enhanced susceptibility to Ang II-induced heart and vascular diseases. Partial loss of ACE2 is sufficient to enhance the susceptibility to

  13. T-lymphocyte induction of human monocyte angiotensin converting enzyme (ACE) is not dependent upon T-lymphocyte proliferation

    SciTech Connect

    Vuk-Pavlovic, Z.; Rohrbach, M.S.

    1986-03-05

    Human peripheral blood monocytes cultured in serum free media for seven days show a basal activity of the ectoenzyme ACE which is augmented 2-3 times by the presence of autologous peripheral blood T-lymphocytes. Since these two cell types are also involved in autologous mixed lymphocyte reaction if serum is present, the authors compared the ability of T-cells to stimulate ACE activity in the presence or absence of proliferation (measured by /sup 3/H-thymidine incorporation). By the seventh day, cultures with 5% AB/sup +/ serum showed significant increase in proliferation but no increase in ACE activity compared to the serum free cultures. Even higher proliferation rate achieved by co-culturing T-lymphocytes with allogeneic monocytes did not increase ACE production; on the contrary, ACE activity remained at the basal level. Monocyte-T-cell co-cultures stimulated with increasing concentrations of ConA or PHA showed dose dependent increases in proliferation but parallel decreases in ACE activity. Addition of soluble antigen (Candida albicans) also enhanced proliferation but not ACE synthesis. They conclude that T-lymphocyte induction of monocyte ACE is a result of cooperation between autologous cells which is not dependent upon T-cell proliferation.

  14. ACE and AGTR1 polymorphisms in elite rhythmic gymnastics.

    PubMed

    Di Cagno, Alessandra; Sapere, Nadia; Piazza, Marina; Aquino, Giovanna; Iuliano, Enzo; Intrieri, Mariano; Calcagno, Giuseppe

    2013-02-01

    In the angiotensin-converting enzyme (ACE) gene, Alu deletion, in intron 16, is associated with higher concentrations of ACE serum activity and this may be associated with elite sprint and power performance. The Alu insertion is associated with lower ACE levels and this could lead to endurance performance. Moreover, recent studies have identified a single-nucleotide polymorphism of the angiotensin type 1 receptor gene AGTR1, which seems to be related to ACE activity. The aim of this study was to examine the involvement of the ACE and the AGTR1 gene polymorphisms in 28 Italian elite rhythmic gymnasts (age range 21 ± 7.6 years), and compare them to 23 middle level rhythmic gymnasts (age range 17 ± 10.9 years). The ACE D allele was significantly more frequent in elite athletes than in the control population (χ(2)=4.07, p=0.04). Comparisons between the middle level and elite athletes revealed significant differences (p<0.0001) for the ACE DD genotype (OR=6.48, 95% confidence interval=1.48-28.34), which was more frequent in elite athletes. There were no significant differences in the AGTR1 A/C genotype or allele distributions between the middle level and elite athletes. In conclusion, the ACE D allele genotype could be a contributing factor to high-performance rhythmic gymnastics that should be considered in athlete development and could help to identify which skills should be trained for talent promotion.

  15. A novel design of combining the angiotensin converting enzyme (ACE) inhibitor captopril with the angiotensin receptor blocker (ARB) losartan using homo coupling via PEG diacid linker.

    PubMed

    Hashemzadeh, Mehrnoosh; Park, Shery; Ju, Hee; Movahed, Mohammad R

    2013-12-01

    Cardiovascular disease is the leading cause of death in American adults. Furthermore, the incidence of congestive heart failure is on the rise as a major cause of hospitalization and mortality in this population. Angiotensin Converting Enzyme (ACE) inhibitors prevent the production of angiotensin II, which has been shown to reduce mortality in patients with congestive heart failure. Angiotensin II receptor blockers (ARB) were developed as a direct inhibitor of angiotensin II. ARBs have been shown to be effective in the treatment of patients with systolic heart failure but do not cause chronic coughing which is a common side effect of ACE inhibitors. In theory, a compound that has the combined effect of an ACE inhibitor and an ARB should be more effective in treating heart failure patients than either agents alone. Therefore, the purpose of this manuscript is to design and discuss the benefits of a new molecule, which combines captopril, an ACE inhibitor, with losartan, an ARB. In this experiment Captopril and Losartan were modified and synthesized separately and combined by homo or mono coupling. This was achieved by taking advantage of PEG (Polyethylene glycol) as a linker. It is expected that this molecule will have the combined modes of action of both ACEs and ARBs. Benefits from combination therapy include; increased efficacy, reduced adverse effects, convenience, compliance, and prolonged duration. Consequently, this combined molecule is expected to block the production of angiotensin II more efficiently and effectively. Although captopril and losartan work in the same system by blocking the effect of angiotensin II they have different action sites and mechanisms some patents are also discussed. Losartan blocks the AT1 receptor which is expressed on the cell surface, while captopril inhibits ACE, preventing production of angiotensin II, which is present in both the plasma and on the cell surface, especially on endothelial and smooth muscle cells.

  16. Surfactant protein A (SP-A) and angiotensin converting enzyme (ACE) as early biomarkers for pulmonary edema formation in ventilated human lung lobes.

    PubMed

    Gnadt, Mirjam; Kardziev, Boris; Schmidt, Michael; Högger, Petra

    2012-08-01

    Ex vivo perfused and ventilated lung lobes frequently develop pulmonary edema. We were looking for a suitable and early detectable biomarker in the perfusion fluid indicating lung cell damage and loss of tissue integrity in ventilated human lung lobes. Therefore, we elucidated whether surfactant protein A (SP-A) and angiotensin-converting enzyme (ACE) were measurable in the perfusion fluid and whether they were suitable indicators for edema formation occurring within the experimental time frame of 1-2 h. Patients (n = 39) undergoing a lobectomy, bilobectomy or pneumonectomy due to primary bronchial cell carcinoma were included in the studies. Lung lobes were extracorporally ventilated and perfused for up to 2 h. Two different perfusion fluids were used, plain perfusion buffer and perfusion buffer containing packed erythrocytes or buffy coats. Perfusion fluid samples were analyzed for SP-A and ACE using immunoassays served as perfusion fluids. SP-A and ACE concentrations were analyzed in fluid sample sets of 39 and 33 perfusion experiments, respectively. Degrees of edema formation were arbitrarily classified into three groups (≤ 29, 30-59, ≥ 60 % weight gain). The maximum increase of SP-A and ACE concentrations in the perfusate was significantly higher for more pronounced edemas in case of perfusions using a mixture of blood components and buffer. Interestingly, the time courses of ACE and SP-A were highly similar. We suggest that SP-A and ACE are promising early biochemical markers for the development for pulmonary edema formation in the ex vivo lung lobe perfusion.

  17. Angiotensin I-converting enzyme (ACE) inhibitory activity of Fucus spiralis macroalgae and influence of the extracts storage temperature-A short report.

    PubMed

    Paiva, Lisete; Lima, Elisabete; Neto, Ana Isabel; Baptista, José

    2016-11-30

    Recently, increasing attention has been paid to the marine algae as a natural source of novel angiotensin-I converting enzyme (ACE) inhibitors, such as the phlorotannins that are the predominant polyphenols in brown algae. This study reports, for the first time, the ACE inhibition of methanol extract/fractions from Azorean brown algae Fucus spiralis (Fs) determined by HPLC-UV method, their total phenolic content (TPC) quantified as phloroglucinol equivalents (PE) and the effect of the Fs dry powder methanol extracts (Fs-DME) storage temperature on ACE inhibition. The results indicate that the ACE inhibition of Fs-DME decreased by 28.8% and 78.2% when stored during 15days at -80°C and -13°C, respectively, as compared with the activity of Fs-DME at a refrigerated temperature of 6°C and assayed immediately after extraction that showed a value of 80.1±2.1%. This Fs-DME sample was fractionated by ultrafiltration membranes into three molecular weight ranges (<1kDa, 1-3kDa and >3kDa), presenting the fraction>3kDa remarkably high ACE inhibition (88.8±2.4%), TPC value (156.6±1.4mg PE/g of dry weight fraction) and yield. Furthermore, chromatographic and spectrophotometric analyses corroborate that phenolic compounds were present in Fs methanol extract/fractions, and also revealed that phloroglucinol occurs in Fs. The results seem to suggest that Azorean Fs can be a source of powerful ACE-inhibitory phlorotannins with potential impact on public health, particularly on hypertensive patients. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Screening of Zulu medicinal plants for angiotensin converting enzyme (ACE) inhibitors.

    PubMed

    Duncan, A C; Jäger, A K; van Staden, J

    1999-12-15

    Twenty plants used by traditional healers in South Africa for the treatment of high blood pressure were investigated for their anti-hypertensive properties, utilizing the angiotensin converting enzyme assay. A hit rate of 65% was achieved, with the highest inhibition (97%) obtained by Adenopodia spicata leaves. A further seven plants exhibited an inhibition greater than 70% and five more over 50%. The leaves of the plants showed the greatest levels of inhibition. There was little difference in the overall hit rate between ethanolic and aqueous extracts, although in most cases there was a marked difference in activity between aqueous and ethanolic extracts from the same species. Plants exhibiting inhibition levels greater than 50% were further tested for the presence of tannins in order to eliminate possible false positives. Active plants that did not contain tannins were Agapanthus africanus, Agave americana, Clausena anisata, Dietes iridioides, Mesembruanthemum spp., Stangeria eriopus and Tulbaghia violacea.

  19. Tumor necrosis factor-alpha convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2).

    PubMed

    Lambert, Daniel W; Yarski, Mike; Warner, Fiona J; Thornhill, Paul; Parkin, Edward T; Smith, A Ian; Hooper, Nigel M; Turner, Anthony J

    2005-08-26

    Angiotensin-converting enzyme-2 (ACE2) is a critical regulator of heart function and a cellular receptor for the causative agent of severe-acute respiratory syndrome (SARS), SARS-CoV (coronavirus). ACE2 is a type I transmembrane protein, with an extracellular N-terminal domain containing the active site and a short intracellular C-terminal tail. A soluble form of ACE2, lacking its cytosolic and transmembrane domains, has been shown to block binding of the SARS-CoV spike protein to its receptor. In this study, we examined the ability of ACE2 to undergo proteolytic shedding and investigated the mechanisms responsible for this shedding event. We demonstrated that ACE2, heterologously expressed in HEK293 cells and endogenously expressed in Huh7 cells, undergoes metalloproteinase-mediated, phorbol ester-inducible ectodomain shedding. By using inhibitors with differing potency toward different members of the ADAM (a disintegrin and metalloproteinase) family of proteases, we identified ADAM17 as a candidate mediator of stimulated ACE2 shedding. Furthermore, ablation of ADAM17 expression using specific small interfering RNA duplexes reduced regulated ACE2 shedding, whereas overexpression of ADAM17 significantly increased shedding. Taken together, these data provided direct evidence for the involvement of ADAM17 in the regulated ectodomain shedding of ACE2. The identification of ADAM17 as the protease responsible for ACE2 shedding may provide new insight into the physiological roles of ACE2.

  20. Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region.

    PubMed

    Parchwani, Deepak N; Palandurkar, Kamlesh M; Hema Chandan Kumar, D; Patel, Darshan J

    2015-01-01

    Genetic polymorphism as described with angiotensin-converting enzyme gene has been proposed as a putative mediator of diabetic nephropathy. We substantiate the hypothesis that genetic variants of the ACE have significant impacts on diabetic nephropathy. To assess the possible association between the three ACE polymorphic variants and DN in an ethnically homogeneous type 2 diabetic population from Kutch region. A 287-bp insertion/deletion polymorphism in intron 16 of the ACE gene was examined by polymerase chain reaction using a case-control approach conducted with 309 unrelated type 2 diabetic patients of Kutch origin (159 Ahir and 150 Rabari, with >10 years duration of T2DM). Of the patients, 143 had nephropathy {AER >30 mg/day (Ahir, n:73 and Rabari, n:70)} and were considered as cases; all others {n:166 (86 Ahir and 80 Rabari)} were normoalbuminuric (AER <30 mg/day) and were treated as controls. Suitable descriptive statistics was used for different variables. Genotype frequencies in all groups were all in accordance with the Hardy-Weinberg equilibrium. Genotypic distribution was significantly different between cases and controls (Ahir: x(2) :8.87, 2 d.f. p = 0.0118; Rabari: x(2) :11.01, 2 d.f. p = 0.0041). Multivariate logistic regression analysis revealed that DD genotype was a significant and strongest independent predictor of microalbuminuria (Ahir: p = 0.0362, OR = 2.65, 95 % CI 1.89-6.36; Rabari: p = 0.024, OR = 2.81, 95 % CI 1.9-6.65). However, it did not independently change the odds of having macroalbuminuria versus microalbuminuria. Analysis of the association under various genetic models revealed that ACE I/D polymorphic variant contribute to DN susceptibility under recessive mode only. Genetic variation at the ACE locus as D/D variant in intron 16, contribute to an increased risk of nephropathy in T2DM patients but not extent of DN severity, and thus this polymorphism might be considered as genetic risk factors for DN among patients

  1. ACE inhibitors

    MedlinePlus

    ... ACE inhibitors There are many different names and brands of ACE inhibitors. Most work as well as ... urac.org). URAC's accreditation program is an independent audit to verify that A.D.A.M. follows ...

  2. Duplicate use of angiotesin-converting enzyme (ACE) inhibitors in a community-dwelling elderly population in Poland.

    PubMed

    Rajska-Neumann, A; Wieczorowska-Tobis, K; Schulz, M; Breborowicz, A; Grzeskowiak, E; Oreopoulos, D G

    2007-01-01

    In this paper the data on the duplicate use of ACE inhibitors among a community-dwelling elderly population are presented. Using a questionnaire, 1000 subjects were interviewed concerning the use of drugs, 654 females, mean+/-SD age: 72.6+/-6.5 years. They were divided into two groups: Group A (5%) taking at least two ACE inhibitors (n=50) and Group B: those who used either a single ACE inhibitor or no ACE inhibitor (n=950). In Group A, 49 individuals were taking two different ACE inhibitors concomitantly and one was using three. The most commonly used ACE inhibitor was enalapril (29 of 50 subjects). Subjects in Group A consumed significantly more drugs, both of prescription (Rx) and nonprescription (OTC), compared to those in Group B (total means: 8.4+/-2.8 vs. 6.7+/-3.2; p<0.01, Rx means: 6.3+/-2.5 vs. 5.2+/-2.8, p<0.05, OTC means: 2.0+/-1.6 vs. 1.6+/-1.5, p<0.05). Also, they were more likely to have consulted a cardiologist (17/50 vs. 201/950, p<0.05). The duplicate use of ACE inhibitors in 5% of a population of community-dwelling elderly patients seems to be caused by both poor doctor-doctor communication and polypharmacy. This phenomenon could possibly be dangerous especially when potential additive adverse effects are taken into account.

  3. Effects of Common Polymorphisms in the MTHFR and ACE Genes on Diabetic Peripheral Neuropathy Progression: a Meta-Analysis.

    PubMed

    Wu, Shuai; Han, Yan; Hu, Qiang; Zhang, Xiaojie; Cui, Guangcheng; Li, Zezhi; Guan, Yangtai

    2017-05-01

    Diabetic peripheral neuropathy (DPN) is a microvascular complication of diabetes mellitus. The aim of this meta-analysis was to evaluate the effects of methylenetetrahydrofolate reductase (MTHFR) 677 C>T and ACE I/D polymorphisms in the development of DPN. We systematically reviewed published studies on MTHFR 677 C>T and ACE I/D polymorphisms and DPN found in various types of electronic databases. Strengthening the Reporting of Observational studies in Epidemiology (STROBE) quality score systems were used to determine the quality of the articles selected for inclusion. Odds ratios (ORs) and its corresponding 95 % confidence interval (95 % CI) were calculated. We used STATA statistical software (version 12.0, Stata Corporation, College Station, TX, USA) to deal with statistical data. Our results indicated an association of ACE D>I mutation (OR = 1.43, 95 % CI 1.12-1.83, P = 0.004) and MTHFR 677 C>T mutation (OR = 1.43, 95 % CI 1.08-1.90, P = 0.014) with DPN under the allele model, and similar results were also found under the dominant model (all P < 0.05). Subgroup analysis by country indicated that the MTHFR 677 C>T polymorphism may be the main risk factor for DPN in Turkey under four genetic models. ACE D>I mutation was correlated with DPN in Japanese and Pakistani populations in the majority of groups. The relationships of MTHFR 677 C>T and ACE I/D polymorphisms with DPN patients presented in this meta-analyses support the view that the MTHFR and ACE genes might play an important role in the development of DPN.

  4. Angiotensin I-converting enzyme (ACE) inhibitory activity and structural properties of oven- and freeze-dried protein hydrolysate from fresh water fish (Cirrhinus mrigala).

    PubMed

    Elavarasan, K; Shamasundar, B A; Badii, Faraha; Howell, Nazlin

    2016-09-01

    The angiotensin I-converting enzyme (ACE) inhibitory activity and structural properties of oven-dried (OD-FPH) and freeze-dried (FD-FPH) protein hydrolysates derived from fresh water fish (Cirrhinus mrigala) muscle, using papain, were investigated. Amino acid profiles indicated a higher proportion of hydrophobic residues in OD-FPH and hydrophilic residues in FD-FPH samples. Fourier transform infrared (FT-IR) spectra revealed random coil structure in OD-FPH and β-sheet in FD-FPH samples. The approximate molecular weight of peptides in OD-FPH and FD-FPH was in the range of 7030-339Da. The IC50 values for ACE inhibition by OD-FPH and FD-FPH samples were found to be 1.15 and 1.53mg of proteinml(-1), respectively. The ACE-inhibitory activity of OD-FPH was more stable (during sequential digestion, using pepsin and pancreatin) than that of FD-FPH sample. The study suggested that the ACE inhibitory activity of protein hydrolysate was not affected by oven-drying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Significant correlation of angiotensin converting enzyme and glycoprotein IIIa genes polymorphisms with unexplained recurrent pregnancy loss in north of Iran.

    PubMed

    Fazelnia, Shokoufeh; Farazmandfar, Touraj; Hashemi-Soteh, Seyed Mohammad Bagher

    2016-05-01

    Spontaneous abortion is considered as the most complex problem during pregnancy. Thrombophilia is resumed as a cause of recurrent pregnancy loss (RPL). Glycoprotein IIIa (GPIIIa) gene is involved in thrombosis and abortion. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II and is involved in thrombosis. The most common polymorphism in this gene is the insertion/deletion (I/D). In this study, we analyzed the association between ACE I/D and GPIIIa c.98C >T polymorphisms in women with unexplained RPL from the north of Iran. Sample population consisted of 100 women with unexplained RPL and 100 controls. The ACE I/D and GPIIIa c.98C>T polymorphisms were genotyped by TETRA-ARMS PCR. The association between genotypes frequency and RPL were analyzed using χ(2) and exact fisher tests. Associated risk with double genotype combinations was also investigated by binary logistic regression. There was significant association between ACE DD genotype and RPL (OR=2.04; 95% CI=0.94-4.44; p=0.036). ACE D Allele was also significantly associated with the RPL (OR=1.59; 95% CI=1.05-2.41; p=0.013). No significant association was observed between GPIIIa c.98C>T polymorphism and RPL. ACE I/D polymorphism may probably be a prognostic factor in female family members of women with the history of recurrent abortion.

  6. Angiotensin-converting enzyme gene insertion/deletion polymorphism studies in Asian Indian pregnant women biochemically identifies gestational diabetes mellitus.

    PubMed

    Khan, Imran A; Jahan, Parveen; Hasan, Qurratulain; Rao, Pragna

    2014-12-01

    Gestational diabetes mellitus (GDM) is defined as glucose intolerance first recognized during pregnancy. Insertion/deletion (I/D) polymorphism of a 287 bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been widely investigated in Asian Indian populations with different ethnic origins. The present study examined possible association between I/D polymorphism of the ACE gene and GDM in Asian Indian pregnant women. A total of 200 pregnant women (100 GDM and 100 non-GDM) were recruited in this study and I/D polymorphism of a 287 bp Alu1 element inside intron 16 of the ACE gene was examined by polymerase chain reaction (PCR)-based gel electrophoresis. The distribution of the variants like II, ID, and DD genotypes of ACE gene showed differences between normal GDM versus non-GDM subjects, and the frequency of the ID+ DD Vs II genotype was significant (p=0.0002) in the GDM group. ACE gene polymorphism was associated with GDM in Asian Indian pregnant women. © The Author(s) 2013.

  7. The association of ACE, ACTN3 and PPARA gene variants with strength phenotypes in middle school-age children.

    PubMed

    Ahmetov, Ildus I; Gavrilov, Dmitry N; Astratenkova, Irina V; Druzhevskaya, Anastasiya M; Malinin, Alexandr V; Romanova, Elena E; Rogozkin, Victor A

    2013-01-01

    The aim of the study was to determine the association between ACE I/D, ACTN3 R577X and PPARA intron 7 G/C gene polymorphisms and strength-related traits in 457 middle school-age children (219 boys and 238 girls; aged 11 ± 0.4 years). The assessment of different phenotypes was conducted with a number of performance tests. Gene polymorphisms were determined by PCR. The ACE D allele was associated with high results of standing long-jump test in boys [II 148.3 (16.3) cm, ID 152.6 (19.6) cm, DD 158.2 (19.1) cm; P = 0.037]. The ACTN3 R allele was associated with high results of performance tests in males only in combination with other genes (standing long-jump test: P = 0.021; handgrip strength test: P < 0.0001). Furthermore, the male carriers of the PPARA gene C allele demonstrated the best results of handgrip strength testing than GG homozygotes [GG 14.6 (4.0) kg, GC/CC 15.7 (4.3) kg; P = 0.048]. Thus, the ACE, ACTN3 and PPARA gene variants are associated with strength-related traits in physically active middle school-age boys.

  8. Distribution of performance-related gene polymorphisms (ACTN3 R577X and ACE ID) in different ethnic groups of the Indian Army.

    PubMed

    Bhagi, Shuchi; Srivastava, Swati; Sarkar, Soma; Singh, Shashi Bala

    2013-01-01

    India has a heterogeneous geographical location with varying ethnic groups with distinct genetic pools. Polymorphisms R577X and insertion/deletion (I/D), occurring in α-actinin3 (ACTN3) and angiotensin converting enzyme (ACE) genes, respectively, are reportedly associated with sprint and endurance performance. The normative genetic background of a population provides the baseline genetic diversity of the population. We investigated the distribution of R577X and I/D polymorphisms in four Indian ethnic populations employed in the Indian Army that requires high levels of physical fitness. A total of 598 army subjects with four different ethnicities were recruited for the study: Rajputs, South Indians, Gorkhas, and Ladakhis. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism followed by statistical analysis. The present study reports for the first time the genotypic distribution of ACTN3 R577X polymorphism in four ethnic groups of the Indian population with no significant change in distribution of R and X alleles among these groups and their overall percentage bearing similarity with the Caucasian population. ACE I/D polymorphism showed significant differences between Rajputs and Gorkhas, Rajputs and Ladakhis, Gorkhas and South Indians, and South Indians and Ladakhis. Combined genotypic analysis showed the highest frequencies of ID+RX in all ethnic groups. Our study reports the genetic predominance of ACE I allele in Gorkhas and I allele predominance in Ladakhis for the first time, thus suggesting that they could be better endurance performers. Both these ethnic groups evolved from the Mongolian race and hence could have similar genotypic distribution. This study provides a comparative account of the Indian normative genetic data in performance-related genes.

  9. Associations between genetic variants in the ACE, AGT, AGTR1 and AGTR2 genes and renal function in the Multi-ethnic Study of Atherosclerosis.

    PubMed

    Campbell, Catherine Y; Fang, Belle F; Guo, Xiuqing; Peralta, Carmen A; Psaty, Bruce M; Rich, Stephen S; Young, J Hunter; Coresh, Josef; Kramer, Holly J; Rotter, Jerome I; Post, Wendy S

    2010-01-01

    Some studies suggest that polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AGTR1) and angiotensin II type II receptor (AGTR2) genes may contribute to renal function variation. Genotyping for single nucleotide polymorphisms (SNPs) in these candidate genes was performed in 2,847 participants from four racial/ethnic groups (African American, Chinese, White and Hispanic) without known cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. SNP and haplotype analyses were performed to determine associations between genotypes and cross-sectional renal function measurements, including urine albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C. Twenty-four ACE SNPs, 10 AGT SNPs, 15 AGTR1 SNPs and 6 AGTR2 SNPs were typed successfully. After adjusting for ancestry, age and gender, 3 SNPs (AGT M235T, AGT rs2148582 and AGTR1 rs2131127) showed associations with an empiric p value <0.05 with the same phenotype in multiple racial/ethnic groups, suggesting replication. The AGT M235T SNP has been shown previously to be associated with diabetic and hypertensive nephropathy. These data suggest that genetic polymorphisms in the renin-angiotensin system are associated with renal phenotypes in the general population, but that many associations differ across racial/ethnic groups. 2010 S. Karger AG, Basel.

  10. Associations between Genetic Variants in the ACE, AGT, AGTR1 and AGTR2 Genes and Renal Function in the Multi-Ethnic Study of Atherosclerosis

    PubMed Central

    Campbell, Catherine Y.; Fang, Belle F.; Guo, Xiuqing; Peralta, Carmen A.; Psaty, Bruce M.; Rich, Stephen S.; Young, J. Hunter; Coresh, Josef; Kramer, Holly J.; Rotter, Jerome I.; Post, Wendy S.

    2010-01-01

    Background/Aims Some studies suggest that polymorphisms in angiotensin-converting enzyme (ACE), angiotensinogen (AGT), angiotensin II type I receptor (AGTR1) and angiotensin II type II receptor (AGTR2) genes may contribute to renal function variation. Methods Genotyping for single nucleotide polymorphisms (SNPs) in these candidate genes was performed in 2,847 participants from four racial/ethnic groups (African American, Chinese, White and Hispanic) without known cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. SNP and haplotype analyses were performed to determine associations between genotypes and cross-sectional renal function measurements, including urine albumin excretion (UAE) and estimated glomerular filtration rate (eGFR) using serum creatinine and cystatin C. Results Twenty-four ACE SNPs, 10 AGT SNPs, 15 AGTR1 SNPs and 6 AGTR2 SNPs were typed successfully. After adjusting for ancestry, age and gender, 3 SNPs (AGT M235T, AGT rs2148582 and AGTR1 rs2131127) showed associations with an empiric p value <0.05 with the same phenotype in multiple racial/ethnic groups, suggesting replication. The AGT M235T SNP has been shown previously to be associated with diabetic and hypertensive nephropathy. Conclusions: These data suggest that genetic polymorphisms in the renin-angiotensin system are associated with renal phenotypes in the general population, but that many associations differ across racial/ethnic groups. PMID:20606419

  11. Gene polymorphisms of adducin GLY460TRP, ACE I/D, AND AGT M235T in pediatric hypertension patients.

    PubMed

    Kaplan, İbrahim; Sancaktar, Enver; Ece, Aydın; Şen, Velat; Tekkeşin, Nilgün; Basarali, Mustafa Kemal; Kelekci, Selvi; Evliyaoglu, Osman

    2014-09-28

    Hypertension is a major global public health problem that affects both pediatric and adult populations. ACE I/D, AGT M235T, and ADD Gly460Trp polymorphisms are thought to be associated with primary hypertension. In the present study, we examined the frequency of these polymorphisms in a pediatric population with secondary hypertension. Included in the study were 58 hypertensive and 58 normotensive pediatric patients. ACE I/D and AGT M235T polymorphisms are determined by conventional PCR; ADD Gly460Trp polymorphism was investigated using PCR amplification of genomic DNA. There were significant differences between the control group and pediatric hypertensive group in terms of ACE I/D (P<0.05) and AGT M235T (P<0.05) polymorphisms, but there were no differences in ADD Gly460Trp (P>0.05) polymorphism. We suggest that RAS gene polymorphisms (ACE-I/D, AGT M235T) are significantly associated with susceptibility to diseases that lead to secondary hypertension.

  12. [Protective Effect of Angiotensin Converting Enzyme 2 (ACE2) Against Chronic Intermittent Hypoxia-induced Pulmonary Oxidative Stress Injury in Rats].

    PubMed

    Kou, Yu-le; Zhang, Pan-pan; Wang, Hong-yang; Zhang, Jia-bin; Tan, Xi-shu; Huang, Chao; Zhang, Min

    2016-01-01

    To determine changes of angiotensin converting enzyme 2 (ACE2) in the development of chronic intermittent hypoxia (CIH)-induced pulmonary injury in rats and its mechanism. 96 adult male Wistar rats were randomly allocated into four groups: control (UC) group, chronic intermittent hypoxia (CIH) group, normal saline treated CIH (NS) group, and edaravone treated CIH (NE) group. Each group contained four subgroups of rats (n = 6) subjecting to 1 week, 2 weeks, 3 weeks, and 4 weeks experiment, respectively. No intervention was given to rats in the UC group. Rats in the experimental groups were exposed to alternating cycles of nitrogen and compressed air. Rats in the NS and NE groups received daily injection of 0.9% normal saline (3 mg/ kg) and edaravone (3 mg/kg), respectively. Pulmonary sections were taken and stained with hematoxylin-eosin (HE). The levels of malondialdehyde (MDA), ACE2, ACE2 mRNA, and angiotensin II (Ang II) mRNA in the rat homogenate pulmonary samples were measured. Rats in the CIH and NS groups showed high levels of interstitial edema, alveolar atelectasis, and inflammatory cell infiltration in alveolar epithelial cells. The pulmonary injury got worse over time. Rats in the NE group showed later occurrence-and milder pulmonary injury compared with those in the NS group. Rats in the CIH and NS groups had higher levels of MDA and Ang II mRNA (which increased over time) than those in the UC group (P < 0.05). The expression of ACE2 and the level of ACE2 mRNA increased in rats in the CIH group (P < 0.05), and peaked at 2 weeks (P < 0.05). Rats in the NE group had moderately increased levels of MDA and Ang II mRNA compared with those in the NS group (P < 0.05); moderately increased levels of expression of ACE2 and ACE2 mRNA compared with those in the UC and SC groups (P < 0.05). The pulmonary level of Ang II mRNA was positively correlated with MDA (r = 0.782, P < 0.01) in rats in the CIH group. CIH can activate oxidation stress and Ang II, which maybe an

  13. The higher exercise intensity and the presence of allele I of ACE gene elicit a higher post-exercise blood pressure reduction and nitric oxide release in elderly women: an experimental study

    PubMed Central

    2011-01-01

    Background The absence of the I allele of the angiotensin converting enzyme (ACE) gene has been associated with higher levels of circulating ACE, lower nitric oxide (NO) release and hypertension. The purposes of this study were to analyze the post-exercise salivary nitrite (NO2-) and blood pressure (BP) responses to different exercise intensities in elderly women divided according to their ACE genotype. Methods Participants (n = 30; II/ID = 20 and DD = 10) underwent three experimental sessions: incremental test - IT (15 watts workload increase/3 min) until exhaustion; 20 min exercise 90% anaerobic threshold (90% AT); and 20 min control session without exercise. Volunteers had their BP and NO2- measured before and after experimental sessions. Results Despite both intensities showed protective effect on preventing the increase of BP during post-exercise recovery compared to control, post-exercise hypotension and increased NO2- release was observed only for carriers of the I allele (p < 0.05). Conclusion Genotypes of the ACE gene may exert a role in post-exercise NO release and BP response. PMID:22136292

  14. Purification and characterisation of a novel angiotensin-I converting enzyme (ACE)-inhibitory peptide derived from the enzymatic hydrolysate of Enteromorpha clathrata protein.

    PubMed

    Pan, Saikun; Wang, Shujun; Jing, Lingling; Yao, Dongrui

    2016-11-15

    Hydrolysates containing angiotensin-I converting enzyme (ACE)-inhibitory peptide were prepared from Enteromorpha clathrata protein using alcalase. The hydrolysates were fractionated into two molecular-weight ranges (below and above 10kDa) by ultrafiltration. The below-10kDa fraction showed higher ACE-inhibitory activity and was subsequently purified by Sephadex G-15 gel filtration chromatography. The structure of active peptide was identified as Pro-Ala-Phe-Gly by HPLC-Q-TOF-MS and its IC50 value was 35.9μM. The yield of this peptide from E. clathrata protein was 0.82%. Lineweaver-Burk plots demonstrated that the inhibitory kinetic mechanism of this peptide was non-competitive. Stability study revealed that the purified peptide showed resistance against gastrointestinal proteases. Thus, E. clathrata protein hydrolysate treated with alcalase is a beneficial ingredient of nutraceuticals and pharmaceuticals against hypertension and related diseases.

  15. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats.

    PubMed

    Sadegh Vishkaei, Mahdokht; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2016-09-30

    Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats' heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension.

  16. Angiotensin-I Converting Enzyme (ACE) Inhibitory and Anti-Hypertensive Effect of Protein Hydrolysate from Actinopyga lecanora (Sea Cucumber) in Rats

    PubMed Central

    Sadegh Vishkaei, Mahdokht; Ebrahimpour, Afshin; Abdul-Hamid, Azizah; Ismail, Amin; Saari, Nazamid

    2016-01-01

    Food protein hydrolysates are known to exhibit angiotensin converting enzyme (ACE) inhibitory properties and can be used as a novel functional food for prevention of hypertension. This study evaluated the ACE inhibitory potentials of Actinopyga lecanora proteolysate (ALP) in vivo. The pre-fed rats with ALP at various doses (200, 400, 800 mg/kg body weight) exhibited a significant (p ≤ 0.05) suppression effect after inducing hypertension. To determine the optimum effective dose that will produce maximal reduction in blood pressure, ALP at three doses was fed to the rats after inducing hypertension. The results showed that the 800 mg/kg body weight dose significantly reduced blood pressure without noticeable negative physiological effect. In addition, there were no observable changes in the rats’ heart rate after oral administration of the ALP. It was concluded that Actinopyga lecanora proteolysate could potentially be used for the development of functional foods and nutraceuticals for prevention and treatment of hypertension. PMID:27706040

  17. Influence of ACE gene on differential response to sertraline versus fluoxetine in patients with major depression: a randomized controlled trial.

    PubMed

    Bahramali, Ehsan; Firouzabadi, Negar; Yavarian, Ilnaz; Shayesteh, Mohammad Reza Hooshangi; Erfani, Nasrallah; Shoushtari, Ali Alavi; Asadpour, Roja

    2016-09-01

    Extensive distribution of the different components of renin angiotensin system (RAS) in the brain, along with their roles in promoting anxiety, depression and brain inflammation, opposes RAS as a potential therapeutic target in major depression. Actions of angiotensin II, the main product of RAS, are reduced by antidepressants and this signifies the complex interplay of different mechanisms involved in response to therapy. Here, we hypothesized that genetic polymorphisms of RAS may affect the outcome of therapy in depressed patients. The frequencies of variants of genes encoding for angiotensin-converting enzyme (ACE) insertion/deletion (I/D), rs4291 and rs4343 polymorphisms were determined in extracted DNAs of 200 newly diagnosed depressed patients. Patients were randomly divided into two groups, one treated with fluoxetine and the other treated with sertraline for 12 weeks. Responsive patients were determined by psychiatrist using Hamilton questionnaire and were compared with regard to their genetic variants. Carriers of the D allele and patients with DD genotype responded significantly better to sertraline than to fluoxetine (P = 0.0006, odds ratio (OR) = 3.0, 95 % confidence interval (CI) = 1.80-5.08; P = 0.006, OR = 3.7, 95 % CI = 1.66-8.29, respectively). Mutant genotypes (GG and TT) of rs4343 and rs4291 polymorphisms were also more frequent in patients responding to sertraline, though not achieving the significance level (P = 0.162 and P = 0.256, respectively). These findings suggest that special genetic variants of RAS may influence or be an indicator for better response to sertraline.

  18. Analysis of Polymorphism of Angiotensin System Genes (ACE, AGTR1, and AGT) and Gene ITGB3 in Patients with Arterial Hypertension in Combination with Metabolic Syndrome.

    PubMed

    Zotova, T Yu; Kubanova, A P; Azova, M M; Aissa, A Ait; Gigani, O O; Frolov, V A

    2016-07-01

    Changes in the frequencies of genotypes and mutant alleles of ACE, AGTR1, AGT, and ITGB3 genes were analyzed in patients with arterial hypertension coupled with metabolic syndrome (N=15) and compared with population data and corresponding parameters in patients with isolated hypertension (N=15). Increased frequency of genotype ID of ACE gene (hypertension predictor) was confirmed for both groups. In case of isolated hypertension, M235M genotype (gene AGT) was more frequent, in case of hypertension combined with metabolic syndrome, the frequency of genotypes A1166C and C1166C of the gene AGTR1 was higher in comparison with population data. Comparison of mutant allele frequencies in the two groups showed that at the 90% significance level allele T of the AGT gene was more frequent in hypertension coupled with metabolic syndrome (OR=1.26) and genotype A1166A of the AGTR1 gene was more frequent in the group with isolated hypertension.

  19. Dynamics of ADAM17-Mediated Shedding of ACE2 Applied to Pancreatic Islets of Male db/db Mice

    PubMed Central

    Pedersen, Kim Brint; Chodavarapu, Harshita; Porretta, Constance; Robinson, Leonie K.

    2015-01-01

    Angiotensin-converting enzyme 2 (ACE2) gene therapy aimed at counteracting pancreatic ACE2 depletion improves glucose regulation in two diabetic mouse models: db/db mice and angiotensin II-infused mice. A disintegrin and metalloproteinase 17 (ADAM17) can cause shedding of ACE2 from the cell membrane. The aim of our studies was to determine whether ADAM17 depletes ACE2 levels in pancreatic islets and β-cells. Dynamics of ADAM17-mediated ACE2 shedding were investigated in 832/13 insulinoma cells. Within a wide range of ACE2 expression levels, including the level observed in mouse pancreatic islets, overexpression of ADAM17 increases shed ACE2 and decreases cellular ACE2 levels. We provide a mathematical description of shed and cellular ACE2 activities as a function of the ADAM17 activity. The effect of ADAM17 on the cellular ACE2 content was relatively modest with an absolute control strength value less than 0.25 and approaching 0 at low ADAM17 activities. Although we found that ADAM17 and ACE2 are both expressed in pancreatic islets, the β-cell is not the major cell type expressing ACE2 in islets. During diabetes progression in 8-, 12-, and 15-week-old db/db mice, ACE2 mRNA and ACE2 activity levels in pancreatic islets were not decreased over time nor significantly decreased compared with nondiabetic db/m mice. Levels of ADAM17 mRNA and ADAM17 activity were also not significantly changed. Inhibiting basal ADAM17 activity in mouse islets failed to affect ACE2 levels. We conclude that whereas ADAM17 has the ability to shed ACE2, ADAM17 does not deplete ACE2 from pancreatic islets in diabetic db/db mice. PMID:26441236

  20. Association of angiotensin converting enzyme gene insertion/deletion polymorphism and familial hypercholesterolemia in the Saudi population

    PubMed Central

    2013-01-01

    Background The study of the association between genotype and phenotype is of great importance for the prediction of multiple diseases and pathophysiological conditions. The relationship between angiotensin converting enzyme (ACE) Insertion/Deletion (I/D) polymorphism and Familial Hypercholesterolemia (FH) has been not fully investigated in all the ethnicities. In this study we sought to determine the frequency of I/D polymorphism genotypes of ACE gene in Saudi patients with FH. Results This is a case–control study carried out purely in Saudi population. Genomic DNA was isolated from 128 subjects who have participated in this study. ACE gene I/D polymorphism was analyzed by polymerase chain reaction in 64 FH cases and 64 healthy controls. There was no statistically significant difference between the groups with respect to genotype distribution. Furthermore, we did not find any significant difference in the frequency of ACE I/D polymorphism in FH subjects when stratified by gender (p = 0.43). Conclusion Our data suggest that ACE gene I/D polymorphism examined in this study has no role in predicting the occurrence and diagnosis of FH. PMID:24289455

  1. ACE insertion/deletion (I/D) polymorphism and diabetic nephropathy.

    PubMed

    Rahimi, Zohreh

    2012-10-01

    Angiotensin converting enzyme (ACE) gene encodes ACE, a key component of renin angiotensin system (RAS), plays an important role in blood pressure homeostasis by generating the vasoconstrictor peptide angiotensin II. Directory of Open Access Journals (DOAJ), Google Scholar, Pubmed (NLM), LISTA (EBSCO) and Web of Science have been searched. The presence of ACE insertion/deletion (I/D) polymorphism affects the plasma level of ACE. ACE DD genotype is associated with the highest systemic and renal ACE levels compared with the lowest ACE activity in carriers of II genotype. In this review focus has been performed on the study of ACE I/D polymorphism in various populations and its influence on the risk of onset and progression of diabetic nephropathy. Also, association between ACE I/D polymorphism and response to ACE inhibitor and angiotensin II receptor antagonists will be reviewed. Further, synergistic effect of this polymorphism and variants of some genes on the risk of development of diabetic nephropathy will be discussed.

  2. Enzymes are enriched in bacterial essential genes.

    PubMed

    Gao, Feng; Zhang, Randy Ren

    2011-01-01

    Essential genes, those indispensable for the survival of an organism, play a key role in the emerging field, synthetic biology. Characterization of functions encoded by essential genes not only has important practical implications, such as in identifying antibiotic drug targets, but can also enhance our understanding of basic biology, such as functions needed to support cellular life. Enzymes are critical for almost all cellular activities. However, essential genes have not been systematically examined from the aspect of enzymes and the chemical reactions that they catalyze. Here, by comprehensively analyzing essential genes in 14 bacterial genomes in which large-scale gene essentiality screens have been performed, we found that enzymes are enriched in essential genes. Essential enzymes have overrepresented ligases (especially those forming carbon-oxygen bonds and carbon-nitrogen bonds), nucleotidyltransferases and phosphotransferases, while have underrepresented oxidoreductases. Furthermore, essential enzymes tend to associate with more gene ontology domains. These results, from the aspect of chemical reactions, provide further insights into the understanding of functions needed to support natural cellular life, as well as synthetic cells, and provide additional parameters that can be integrated into gene essentiality prediction algorithms.

  3. Simulated digestion of proanthocyanidins in grape skin and seed extracts and the effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory activity.

    PubMed

    Fernández, Katherina; Labra, Javiera

    2013-08-15

    This study investigated the effect of in vitro gastrointestinal digestion on the stability and composition of flavan-3-ols from red grape skin and seed extracts (raw and purified, which are high in proanthocyanidins (PAs)). In addition, the effects of digestion on the angiotensin I-converting enzyme (ACE) inhibitory activities of these extracts were evaluated. The extracts were digested with a mixture of pepsin-HCl for 2 h, followed by a 2 h incubation with pancreatin and bile salts including a cellulose dialysis tubing (molecular weight cut-off 12 kDa) at 37°C with shaking in the dark and under N2. Under gastric conditions, the mean degree of polymerisation (mDP) of seed extracts, raw (mDP≈6, p<0.05), and purified (mDP≈10, p<0.05) was stable. The mDP of the raw skin extracts increased from 19 to 25 towards the end of the digestion. The PAs were significantly degraded (up to 80%) during the pancreatic digestion, yielding low-molecular-weight compounds that diffused into the serum-available fraction (mDP≈2). The overall mass transfer coefficient (K) of the seed extracts was 10(-7) m(2)/s. After simulated gastrointestinal digestion, over 80% of ACE inhibition by raw seed and skin extracts was preserved. However, the purified seed and skin extracts lost their ability to inhibit ACE after intestinal digestion.

  4. Diagnostic use of angiotensin converting enzyme (ACE)-inhibited renal scintigraphy in the identification of selective renal artery stenosis in the presence of multiple renal arteries: A case report

    SciTech Connect

    Morton, K.A.; Rose, S.C.; Haakenstad, A.O.; Handy, J.E.; Scuderi, A.J.; Datz, F.L. )

    1990-11-01

    In patients with renovascular hypertension, it is unknown whether the angiotensin converting enzyme-(ACE) inhibited renal scan will identify stenosis of a segmental branch of a single renal artery or of an accessory artery where multiple renal arteries are present. Since multiple renal arteries may be present in approximately 25% of all individuals, it will be important to establish whether the ACE-inhibited renal scan is useful in this population. We report a case of stenosis involving a renal artery in a patient with multiple renal arteries, successfully identified by ACE-inhibited renal scintigraphy.

  5. ACTN3 R577X and ACE I/D gene variants influence performance in elite sprinters: a multi-cohort study.

    PubMed

    Papadimitriou, Ioannis D; Lucia, Alejandro; Pitsiladis, Yannis P; Pushkarev, Vladimir P; Dyatlov, Dmitry A; Orekhov, Evgeniy F; Artioli, Guilherme G; Guilherme, João Paulo L F; Lancha, Antonio H; Ginevičienė, Valentina; Cieszczyk, Pawel; Maciejewska-Karlowska, Agnieszka; Sawczuk, Marek; Muniesa, Carlos A; Kouvatsi, Anastasia; Massidda, Myosotis; Calò, Carla Maria; Garton, Fleur; Houweling, Peter J; Wang, Guan; Austin, Krista; Druzhevskaya, Anastasiya M; Astratenkova, Irina V; Ahmetov, Ildus I; Bishop, David J; North, Kathryn N; Eynon, Nir

    2016-04-13

    To date, studies investigating the association between ACTN3 R577X and ACE I/D gene variants and elite sprint/power performance have been limited by small cohorts from mixed sport disciplines, without quantitative measures of performance. To examine the association between these variants and sprint time in elite athletes. We collected a total of 555 best personal 100-, 200-, and 400-m times of 346 elite sprinters in a large cohort of elite Caucasian or African origin sprinters from 10 different countries. Sprinters were genotyped for ACTN3 R577X and ACE ID variants. On average, male Caucasian sprinters with the ACTN3 577RR or the ACE DD genotype had faster best 200-m sprint time than their 577XX (21.19 ± 0.53 s vs. 21.86 ± 0.54 s, p = 0.016) and ACE II (21.33 ± 0.56 vs. 21.93 ± 0.67 sec, p = 0.004) counterparts and only one case of ACE II, and no cases of ACTN3 577XX, had a faster 200-m time than the 2012 London Olympics qualifying (vs. 12 qualified sprinters with 577RR or 577RX genotype). Caucasian sprinters with the ACE DD genotype had faster best 400-m sprint time than their ACE II counterparts (46.94 ± 1.19 s vs. 48.50 ± 1.07 s, p = 0.003). Using genetic models we found that the ACTN3 577R allele and ACE D allele dominant model account for 0.92 % and 1.48 % of sprint time variance, respectively. Despite sprint performance relying on many gene variants and environment, the % sprint time variance explained by ACE and ACTN3 is substantial at the elite level and might be the difference between a world record and only making the final.

  6. Influence of the ACE gene insertion/deletion polymorphism on insulin sensitivity and impaired glucose tolerance in healthy subjects.

    PubMed

    Bonnet, Fabrice; Patel, Sheila; Laville, Martine; Balkau, Beverley; Favuzzi, Angela; Monti, Lucilla D; Lalic, Nebojsa; Walker, Mark

    2008-04-01

    Recent studies suggested that the blockade of the renin-angiotensin system (RAS) may be associated with metabolic benefits. However, data about the potential influence of the ACE insertion/deletion (I/D) genotype on insulin resistance have been contradictory with studies of limited sample sizes. The purpose of this study was to investigate the relationship between the ACE gene I/D polymorphism and both insulin sensitivity and glucose intolerance in a large cohort of healthy subjects. A total of 1,286 participants in the Relationship Between Insulin Sensitivity and Cardiovascular Disease Risk Study had a 75-g oral glucose tolerance test and a hyperinsulinemic-euglycemic clamp to assess whole-body insulin sensitivity. Age, BMI, waist, fat-free mass (ffm), and physical activity did not differ by ACE genotype. Fasting glucose and insulin were similar among genotypes, but 2-h glucose levels were higher in DD than in ID and II subjects (DD: 5.9 +/- 1.7; ID: 5.7 +/- 1.5; II: 5.6 +/- 1.5 mmol/l) (P = 0.004). Participants with the DD genotype were more likely to have impaired glucose tolerance than those with the ID and II genotypes (13.1 vs. 8.7%; P = 0.02). Insulin sensitivity was lower in participants with the DD genotype than in those with the II genotype (136 +/- 63 vs. 147 +/- 65 micromol x min(-1)x kg ffm(-1) x mmol(-1) x l(-1); P = 0.02). The presence of the D allele was associated with a trend, albeit not significant, for reduced insulin secretion during the oral glucose tolerance test (P = 0.07). The ACE I/D polymorphism is associated with whole-body insulin sensitivity and with impaired glucose tolerance in our healthy population. These findings confirm potential interactions between the RAS and glucose metabolism.

  7. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia.

    PubMed

    Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

    2017-01-01

    Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases.

  8. Association between ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133), FTO (rs9939609) Genes Polymorphism and Type 2 Diabetes with Dyslipidemia

    PubMed Central

    Raza, Syed Tasleem; Abbas, Shania; Siddiqi, Zeba; Mahdi, Farzana

    2017-01-01

    Diabetic dyslipidemia is one of the leading causes of coronary artery disease (CAD) death. Genetic and environmental factors play an important role in the development of type 2 diabetes mellitus (T2DM) and dyslipidemia. The present study was aimed to investigate the association of ACE (rs4646994), FABP2 (rs1799883), MTHFR (rs1801133) and FTO (rs9939609) genes polymorphism in T2DM with dyslipidemia. Totally, 559 subjects including 221 T2DM cases with dyslipidemia, 158 T2DM without dyslipidemia and 180 controls were enrolled. ACE genes polymorphism was evaluated by polymerase chain reaction (PCR), while MTHFR, FABP2, FTO genes polymorphisms were evaluated by PCR and restriction fragment length polymorphism (RFLP). Significant association of ACE and MTHFR genes polymorphisms were found in both group of cases [T2DM with dyslipidemia (P<0.001, and P=0.008, respectively) and T2DM without dyslipidemia (P=0.003, and P=0.010, respectively)] while FABP2 and FTO genes polymorphisms were significantly associated with T2DM without dyslipidemia (P=0.038, and P= 0.019, respectively). This study concludes that ACE, FABP2, FTO and MTHFR genes are associated with T2DM. Additionally, it also seems that ACE and MTHFR genes might be further associated with the development of dyslipidemia in T2DM cases. PMID:28890888

  9. Influence of erroneous fractional product extraction values on the estimation of angiotensin converting enzyme (ACE) substrate utilization

    SciTech Connect

    Catravas, J.D.; Ryan, J.W.; Chen, X.L.; Orphanos, S.E.; Chung, A.Y.K. Univ. of Miami, FL )

    1990-02-26

    Kinetic parameters of endothelial or plasma ACE can be estimated from the hydrolysis of radiolabeled substrates (S), e.g., {sup 3}H-benzoyl-Phe-Ala-Pro (BPAP) to {sup 3}H-benzoyl-Phe and subsequent extraction of product from an acidified aqueous phase into toluene. Since fractional S (f{sub s}) and product (f{sub p}) extraction values, used to calculate S utilization, vary widely with duration and temperature of extraction and ratio of aqueous to organic phase, the authors investigated the effect of using erroneous f{sub s} or f{sub p} values on calculated BPAP hydrolysis by guinea pig and rabbit plasma ACE in vitro, under first order reaction conditions. Deviations as little as 0.03 from the actual f{sub p} value (0.61: 48 hours, single vial extraction at 23C, 1:1 aqueous (0.12N HCl) : 4% omnifluor in toluene) caused serious miscalculations in S utilization, ((S{sub o}) and (S) are initial and final S concentrations, respectively) particularly at levels of BPAP hydrolysis normally observed in vivo (>70%). Similar deviations in f{sub s} had no significant effect on computation of BPAP hydrolysis. This was true with both guinea pig and rabbit plasma ACE, and, utilizing the actual f{sub p} and f{sub s} (0.05, under identical conditions) values, BPAP concentration declined logarithmically to undetectable levels (more than 99% S utilization) as predicted by Michaelis-Menten kinetics.

  10. Human gut endogenous proteins as a potential source of angiotensin-I-converting enzyme (ACE-I)-, renin inhibitory and antioxidant peptides.

    PubMed

    Dave, Lakshmi A; Hayes, Maria; Montoya, Carlos A; Rutherfurd, Shane M; Moughan, Paul J

    2016-02-01

    It is well known that endogenous bioactive proteins and peptides play a substantial role in the body's first line of immunological defence, immune-regulation and normal body functioning. Further, the peptides derived from the luminal digestion of proteins are also important for body function. For example, within the peptide database BIOPEP (http://www.uwm.edu.pl/biochemia/index.php/en/biopep) 12 endogenous antimicrobial and 64 angiotensin-I-converting enzyme (ACE-I) inhibitory peptides derived from human milk and plasma proteins are listed. The antimicrobial peptide database (http://aps.unmc.edu/AP/main.php) lists over 111 human host-defence peptides. Several endogenous proteins are secreted in the gut and are subject to the same gastrointestinal digestion processes as food proteins derived from the diet. The human gut endogenous proteins (GEP) include mucins, serum albumin, digestive enzymes, hormones, and proteins from sloughed off epithelial cells and gut microbiota, and numerous other secreted proteins. To date, much work has been carried out regarding the health altering effects of food-derived bioactive peptides but little attention has been paid to the possibility that GEP may also be a source of bioactive peptides. In this review, we discuss the potential of GEP to constitute a gut cryptome from which bioactive peptides such as ACE-I inhibitory, renin inhibitory and antioxidant peptides may be derived. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Haplotype-based association of ACE I/D, AT1R 1166A>C, and AGT M235T polymorphisms in renin-angiotensin-aldosterone system genes in Korean women with idiopathic recurrent spontaneous abortions.

    PubMed

    Choi, Yi Seul; Kwon, Hwang; Kim, Ji Hyang; Shin, Ji Eun; Choi, Youngsok; Yoon, Tae Ki; Choi, Dong Hee; Kim, Nam Keun

    2011-10-01

    The objective of this study was to determine whether or not the angiotensin-converting enzyme insertion/deletion (ACE I/D), angiotensin II type 1 receptor (AT1R), and angiotensinogen (AGT) gene polymorphisms are associated with idiopathic recurrent spontaneous abortions (RSAs) in Korean women. A total of 251 patients with unexplained consecutive pregnancy losses, and 126 healthy controls with at least one live birth and no history of pregnancy loss. The odds ratios (ORs) of the ACE ID (OR=2.423; 95% confidence interval (CI)=1.417-4.142; p=0.001) and the ACE II (OR=2.050; 95% CI=1.143-3.675; p=0.018) for the ACE DD genotype were significantly different between patients with idiopathic RSA and controls; however, there were no significant differences between patients and controls with respect to the AT1R 1166A>C and AGT M235T polymorphisms. In a haplotype-based analysis of I-A (p=0.010), D-A (p=0.004), I-A-T (p=0.033), D-A-T (p=0.0005), and D-C-T (p=0.013) polymorphism pairs with synergistic effects derived by the MDR method in patients and in controls showed significant results. This study suggests that ACE, AT1R and AGT polymorphisms and haplotypes are a genetic determinant for the risk of idiopathic RSA in Korean women. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Correlation of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease: a meta-analysis.

    PubMed

    Tian, Yulong; Ge, Zhongchun; Xing, Yuliang; Sun, Yan; Ying, Jie

    2016-12-01

    Rheumatic heart disease (RHD) is a serious cardiovascular disorder worldwide. Several articles have reported the effect of angiotensin I-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in RHD risk. However, the results still remain inconsistent. The objective of the present study was to assess more precise estimations of the relationship between ACE I/D variant and RHD susceptibility. Relevant case-control studies published between January 2000 and 2016 were searched in the electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of the effect. A total of nine articles were retrieved, including 1333 RHD patients and 1212 healthy controls. Overall, our result did not detect a significant association between ACE I/D polymorphism and RHD risk under each genetic model (P > 0.05). Subgroup analysis by ethnicity showed no positive relationship in Asians as well (P > 0.05). With respect to the severity of RHD, our result found that the frequency differences between mitral valve lesion (MVL), combined valve lesion (CVL) and healthy controls were not significantly different. Furthermore, no significant association was found between female, male RHD patients and the controls regarding to the ACE I/D polymorphism. In conclusion, our result indicated that ACE I/D polymorphism might not be a risk factor for RHD progression based on the existing research results. Additional well-designed studies with larger samples are still needed to confirm these findings.

  13. Correlation of angiotensin I-converting enzyme gene insertion/deletion polymorphism with rheumatic heart disease: a meta-analysis

    PubMed Central

    Tian, Yulong; Ge, Zhongchun; Xing, Yuliang; Sun, Yan; Ying, Jie

    2016-01-01

    Rheumatic heart disease (RHD) is a serious cardiovascular disorder worldwide. Several articles have reported the effect of angiotensin I-converting enzyme gene insertion/deletion (ACE I/D) polymorphism in RHD risk. However, the results still remain inconsistent. The objective of the present study was to assess more precise estimations of the relationship between ACE I/D variant and RHD susceptibility. Relevant case–control studies published between January 2000 and 2016 were searched in the electronic databases. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate the strength of the effect. A total of nine articles were retrieved, including 1333 RHD patients and 1212 healthy controls. Overall, our result did not detect a significant association between ACE I/D polymorphism and RHD risk under each genetic model (P > 0.05). Subgroup analysis by ethnicity showed no positive relationship in Asians as well (P > 0.05). With respect to the severity of RHD, our result found that the frequency differences between mitral valve lesion (MVL), combined valve lesion (CVL) and healthy controls were not significantly different. Furthermore, no significant association was found between female, male RHD patients and the controls regarding to the ACE I/D polymorphism. In conclusion, our result indicated that ACE I/D polymorphism might not be a risk factor for RHD progression based on the existing research results. Additional well-designed studies with larger samples are still needed to confirm these findings. PMID:27758878

  14. Malaysian brown seaweeds Sargassum siliquosum and Sargassum polycystum: Low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase inhibition activities.

    PubMed

    Nagappan, Hemlatha; Pee, Poh Ping; Kee, Sandra Hui Yin; Ow, Ji Tsong; Yan, See Wan; Chew, Lye Yee; Kong, Kin Weng

    2017-09-01

    Two Malaysian brown seaweeds, Sargassum siliquosum and Sargassum polycystum were first extracted using methanol to get the crude extract (CE) and further fractionated to obtain fucoxanthin-rich fraction (FRF). Samples were evaluated for their phenolic, flavonoid, and fucoxanthin contents, as well as their inhibitory activities towards low density lipoprotein (LDL) oxidation, angiotensin converting enzyme (ACE), α-amylase, and α-glucosidase. In LDL oxidation assay, an increasing trend in antioxidant activity was observed as the concentration of FRF (0.04-0.2mg/mL) and CE (0.2-1.0mg/mL) increased, though not statistically significant. As for serum oxidation assay, significant decrease in antioxidant activity was observed as concentration of FRF increased, while CE showed no significant difference in inhibitory activity across the concentrations used. The IC50 values for ACE inhibitory activity of CE (0.03-0.42mg/mL) were lower than that of FRF (0.94-1.53mg/mL). When compared to reference drug Voglibose (IC50 value of 0.61mg/mL) in the effectiveness in inhibiting α-amylase, CE (0.58mg/mL) gave significantly lower IC50 values while FRF (0.68-0.71mg/mL) had significantly higher IC50 values. The α-glucosidase inhibitory activity of CE (IC50 value of 0.57-0.69mg/mL) and FRF (IC50 value of 0.50-0.53mg/mL) were comparable to that of reference drug (IC50 value of 0.54mg/mL). Results had shown the potential of S. siliquosum and S. polycystum in reducing cardiovascular diseases related risk factors following their inhibitory activities on ACE, α-amylase and α-glucosidase. In addition, it is likelihood that FRF possessed antioxidant activity at low concentration level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Increased angiotensin-I converting enzyme gene expression in the failing human heart. Quantification by competitive RNA polymerase chain reaction.

    PubMed Central

    Studer, R; Reinecke, H; Müller, B; Holtz, J; Just, H; Drexler, H

    1994-01-01

    Local activation of the components of the renin angiotensin system in the heart is regarded as an important modulator of cardiac phenotype and function; however, little is known about their presence, regulation, and potential activation in the human heart. To investigate the gene expression of major angiotensin-II-forming enzymes in left ventricles of normal (n = 9) and failing human hearts (n = 20), we established a competitive RNA-polymerase chain reaction (PCR) for mRNA quantification of angiotensin-I converting enzyme (ACE) and human heart chymase. For each gene, competitor RNA targets with small internal deletions were used as internal standards to quantify the original number of transcripts and to control reverse transcription and PCR. In PCR, each target and the corresponding competitor were amplified by competing for the same primer oligonucleotides. The variability of ACE RNA-PCR was 11% indicating a high reproducibility of this method. In addition, ACE mRNA levels obtained by competitive RNA-PCR correlated favorably with traditional slot blot hybridization (r = 0.69, n = 10; P < 0.05). Compared with nonfailing hearts, the number of ACE transcripts referred to 100 ng of total RNA was increased threefold in patients with chronic heart failure (4.2 +/- 2.5 vs. 12.8 +/- 6 x 10(5); P < 0.0005). In contrast, no significant difference was found in chymase gene expression between normal and failing hearts. Thus, the expression of the cardiac ACE but not of human heart chymase is upregulated in failing human heart indicating an activation of the cardiac renin-angiotensin system in patients with advanced heart failure. Images PMID:8040271

  16. Human intestine luminal ACE2 and amino acid transporter expression increased by ACE-inhibitors.

    PubMed

    Vuille-dit-Bille, Raphael N; Camargo, Simone M; Emmenegger, Luca; Sasse, Tom; Kummer, Eva; Jando, Julia; Hamie, Qeumars M; Meier, Chantal F; Hunziker, Schirin; Forras-Kaufmann, Zsofia; Kuyumcu, Sena; Fox, Mark; Schwizer, Werner; Fried, Michael; Lindenmeyer, Maja; Götze, Oliver; Verrey, François

    2015-04-01

    Sodium-dependent neutral amino acid transporter B(0)AT1 (SLC6A19) and imino acid (proline) transporter SIT1 (SLC6A20) are expressed at the luminal membrane of small intestine enterocytes and proximal tubule kidney cells where they exert key functions for amino acid (re)absorption as documented by their role in Hartnup disorder and iminoglycinuria, respectively. Expression of B(0)AT1 was shown in rodent intestine to depend on the presence of the carboxypeptidase angiotensin-converting enzyme 2 (ACE2). This enzyme belongs to the renin-angiotensin system and its expression is induced by treatment with ACE-inhibitors (ACEIs) or angiotensin II AT1 receptor blockers (ARBs) in many rodent tissues. We show here in the Xenopus laevis oocyte expression system that human ACE2 also functionally interacts with SIT1. To investigate in human intestine the potential effect of ACEIs or ARBs on ACE2, we analysed intestinal biopsies taken during routine gastroduodenoscopy and ileocolonoscopy from 46 patients of which 9 were under ACEI and 13 ARB treatment. Analysis of transcript expression by real-time PCR and of proteins by immunofluorescence showed a co-localization of SIT1 and B(0)AT1 with ACE2 in the brush-border membrane of human small intestine enterocytes and a distinct axial expression pattern of the tested gene products along the intestine. Patients treated with ACEIs displayed in comparison with untreated controls increased intestinal mRNA levels of ACE2, peptide transporter PEPT1 (SLC15A1) and AA transporters B(0)AT1 and PAT1 (SLC36A1). This study unravels in human intestine the localization and distribution of intestinal transporters involved in amino acid absorption and suggests that ACEIs impact on their expression.

  17. ACE2 orthologues in non-mammalian vertebrates (Danio, Gallus, Fugu, Tetraodon and Xenopus).

    PubMed

    Chou, Chih-Fong; Loh, Chay Boon; Foo, Yik Khoon; Shen, Shuo; Fielding, Burtram C; Tan, Timothy H P; Khan, Sehaam; Wang, Yue; Lim, Seng Gee; Hong, Wanjin; Tan, Yee-Joo; Fu, Jianlin

    2006-08-01

    Angiotensin-converting enzyme 2 (ACE2), a newly identified member in the renin-angiotensin system (RAS), acts as a negative regulator of ACE. It is mainly expressed in cardiac blood vessels and the tubular epithelia of kidneys and abnormal expression has been implicated in diabetes, hypertension and heart failure. The mechanism and physiological function of this zinc metallopeptidase in mammals are not yet fully understood. Non-mammalian vertebrate models offer attractive and simple alternatives that could facilitate the exploration of ACE2 function. In this paper we report the in silico analysis of Ace2 genes from the Gallus (chicken), Xenopus (frog), Fugu and Tetraodon (pufferfish) genome assembly databases, and from the Danio (zebrafish) cDNA library. Exon ambiguities of Danio and Xenopus Ace2s were resolved by RT-PCR and 3'RACE. Analyses of the exon-intron structures, alignment, phylogeny and hydrophilicity plots, together with the conserved synteny among these vertebrates, support the orthologous relationship between mammalian and non-mammalian ACE2s. The putative promoters of Ace2 from human, Tetraodon and Xenopus tropicalis drove the expression of enhanced green fluorescent protein (EGFP) specifically in the heart tissue of transgenic Xenopus thus making it a suitable model for future functional genomic studies. Additionally, the search for conserved cis-elements resulted in the discovery of WGATAR motifs in all the putative Ace2 promoters from 7 different animals, suggesting a possible role of GATA family transcriptional factors in regulating the expression of Ace2.

  18. Novel approach of molecular genetic understanding of iridology: relationship between iris constitution and angiotensin converting enzyme gene polymorphism.

    PubMed

    Um, Jae-Young; An, Nyeon-Hyoung; Yang, Gui-Bi; Lee, Geon-Mok; Cho, Ju-Jang; Cho, Jae-Woon; Hwang, Woo-Jun; Chae, Han-Jung; Kim, Hyung-Ryong; Hong, Seung-Heon; Kim, Hyung-Min

    2005-01-01

    Iridology is the study of the iris of the eye to detect the conditions of the body and its organs, genetic strengths and weaknesses, etc. Although iridology is not widely used as a scientific tool for healthcare professionals to get to the source of people's health conditions, it has been used as a supplementary source to help the diagnosis of medical conditions by noting irregularities of the pigmentation in the iris among some Korean Oriental medical doctors. Angiotensin converting enzyme (ACE) gene polymorphism is one of the most well studied genetic markers of vascular disease. We investigated the relationship between iridological constitution and ACE polymorphism in hypertensives. We classified 87 hypertensives and 79 controls according to iris constitution and determined the ACE genotype of each individual. DD genotype was more prevalent in patients with a neurogenic constitution than in controls. This finding supports the hypothesis that D allele is a candidate gene for hypertension and demonstrates the association among ACE genotype, Korean hypertensives and iris constitution.

  19. The relationship between ACE polymorphism and panic disorder.

    PubMed

    Gulec-Yılmaz, Seda; Gulec, Huseyın; Dalan, Altay Burak; Cetın, Bugra; Tımırcı-Kahraman, Ozlem; Ogut, Dıcle Bılge; Atasoy, Hande; Dırımen, Gulız Arikan; Gultekın, Guldal Inal; Isbır, Turgay

    2014-01-01

    The angiotensin converting enzyme (ACE) gene, which has been found to have an insertion and deletion polymorphism (I/D), is of increasing interest in etiology and treatment of various psychiatric disorders such as panic disorder. The present study aimed to investigate the relationship between ACE polymorphism and panic disorder. In this study, 43 patients diagnosed with panic disorder at the Erenköy Mental and Neurological Diseases Training and Research Hospital, Istanbul and 41 healthy controls were enrolled. The ACE gene insertion/deletion polymorphism of exon 16 was evaluated using the polymerase chain reaction method. There was a significant association between I/D genotype and panic disorder (p=0.003). However, the frequency of the I allele was found to be significantly higher in patients compared to controls (p=0.002). In addition, we recognized a significant association between I/D polymorphism and respiratory-type panic disorder in patients. Carriers of the D allele also had an increased risk of respiratory type panic disorder patients (p=0.034). Moreover, the result of Spearman correlation analysis showed an association with ACE D allele and severity of panic disorder (p<0.001). We suggest that the I/D polymorphism of the ACE gene is associated with panic disorder and particularly respiratory-type panic disorder in patients. The I/D polymorphism of the ACE gene seems to influence therapeutic outcome in patients suffering from panic disorder. Our results indicate that ACE D allele is associated with the severity of panic disorder. Copyright © 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  20. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment.

    PubMed

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration.

  1. Association of Increased Serum ACE Activity with Logical Memory Ability in Type 2 Diabetic Patients with Mild Cognitive Impairment

    PubMed Central

    Tian, Sai; Han, Jing; Huang, Rong; Xia, Wenqing; Sun, Jie; Cai, Rongrong; Dong, Xue; Shen, Yanjue; Wang, Shaohua

    2016-01-01

    Background: Angiotensin-converting enzyme (ACE) is involved in the chronic complications of type 2 diabetes mellitus (T2DM) and Alzheimer's disease. This study aimed to assess the pathogenetic roles of ACE and the genetic predisposition of its insertion/deletion (I/D) polymorphism in mild cognitive impairment (MCI) among T2DM patients. Methods: A total of 210 T2DM patients were enrolled. Among these patients, 116 satisfied the MCI diagnostic criteria and 94 exhibited healthy cognition. The cognitive functions of the patients were extensively assessed. The serum level and activity of ACE were measured via enzyme-linked immunosorbent assay and ultraviolet spectrophotography. The single-nucleotide polymorphisms of I/D gene of ACE were analyzed. Results: The serum level and activity of ACE in diabetic MCI patients (p = 0.022 and p = 0.008, respectively) were both significantly higher than those in the healthy controls. A significant negative correlation was found between their ACE activity and logical memory test score (LMT) (p = 0.002). Multiple stepwise regression iterated the negative correlation between ACE activity and LMT score (p = 0.035). Although no significant difference was found in the genotype or allele distribution of ACE I/D polymorphism between the groups, the serum levels and activity of ACE were higher in the DD group than in the ID and II groups (p < 0.05). Conclusions: Serum ACE activity could better predict logical memory in T2DM patients than ACE level. Further investigations on a large population size are necessary to test whether the D-allele of the ACE gene polymorphism is susceptible to memory deterioration. PMID:28066203

  2. The critical role of tissue angiotensin-converting enzyme as revealed by gene targeting in mice.

    PubMed Central

    Esther, C R; Marino, E M; Howard, T E; Machaud, A; Corvol, P; Capecchi, M R; Bernstein, K E

    1997-01-01

    Angiotensin-converting enzyme (ACE) generates the vasoconstrictor angiotensin II, which plays a critical role in maintenance of blood pressure in mammals. Although significant ACE activity is found in plasma, the majority of the enzyme is bound to tissues such as the vascular endothelium. We used targeted homologous recombination to create mice expressing a form of ACE that lacks the COOH-terminal half of the molecule. This modified ACE protein is catalytically active but entirely secreted from cells. Mice that express only this modified ACE have significant plasma ACE activity but no tissue-bound enzyme. These animals have low blood pressure, renal vascular thickening, and a urine concentrating defect. The phenotype is very similar to that of completely ACE-deficient mice previously reported, except that the renal pathology is less severe. These studies strongly support the concept that the tissue-bound ACE is essential to the control of blood pressure and the structure and function of the kidney. PMID:9153279

  3. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse

    PubMed Central

    Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

    2017-01-01

    Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS. PMID:28273875

  4. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse.

    PubMed

    Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose

    2017-03-05

    Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS.

  5. AAV8-Mediated Angiotensin-Converting Enzyme 2 Gene Delivery Prevents Experimental Autoimmune Uveitis by Regulating MAPK, NF-κB and STAT3 Pathways

    PubMed Central

    Qiu, Yiguo; Tao, Lifei; Zheng, Shijie; Lin, Ru; Fu, Xinyu; Chen, Zihe; Lei, Chunyan; Wang, Jiaming; Li, Hongwei; Li, Qiuhong; Lei, Bo

    2016-01-01

    Renin angiotensin system (RAS) is a key hormonal system which regulates the cardiovascular function and is implicated in several autoimmune diseases. With the discovery of the angiotensin-converting enzyme 2 (ACE2), a protective axis of RAS namely ACE2/Ang-(1–7)/Mas that counteracts the deleterious ACE/AngII/AT1R axis has been established. This axis is emerging as a novel target to attenuate ocular inflammation. However, the underlying molecular mechanisms remain unclear. We investigated the hypothesis that enhancing the activity of the protective axis of RAS by subretinal delivery of an AAV8 (Y733F)-ACE2 vector would protect against the ocular inflammation in experimental autoimmune uveitis (EAU) mice through regulating the local immune responses. Our studies demonstrated that increased ACE2 expression exerts protective effects on inflammation in EAU mouse by modulating ocular immune responses, including the differentiation of Th1/Th17 cells and the polarization of M1/M2 macrophages; whereas the systemic immune responses appeared not affected. These effects were mediated by activating the Ang-(1–7)/Mas and inhibiting the MAPK, NF-κB and STAT3 signaling pathways. This proof-of-concept study suggests that activation of ocular ACE2/Ang-(1–7)/Mas axis with AAV gene transfer modulates local immune responses and may be a promising, long-lasting therapeutic strategy for refractory and recurrent uveitis, as well as other inflammatory eye diseases. PMID:27558087

  6. [Association of I/D and -786 Polymorphisms of ACE and NOS3 Genes With Features of the Course of Ischemic Heart Disease and Diabetes Mellitus Type 2].

    PubMed

    Afanasiev, S A; Muslimova, E F; Rebrov, T Y; Sergienko, T N; Repin, A N

    2016-09-01

    to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

  7. ACE Phenotyping as a Guide Toward Personalized Therapy With ACE Inhibitors.

    PubMed

    Danilov, Sergei M; Tovsky, Stan I; Schwartz, David E; Dull, Randal O

    2017-07-01

    Angiotensin-converting enzyme (ACE) inhibitors (ACEI) are widely used in the management of cardiovascular diseases but with significant interindividual variability in the patient's response. To investigate whether interindividual variability in the response to ACE inhibitors is explained by the "ACE phenotype"-for example, variability in plasma ACE concentration, activity, and conformation and/or the degree of ACE inhibition in each individual. The ACE phenotype was determined in plasma of 14 patients with hypertension treated chronically for 4 weeks with 40 mg enalapril (E) or 20 mg E + 16 mg candesartan (EC) and in 20 patients with hypertension treated acutely with a single dose (20 mg) of E with or without pretreatment with hydrochlorothiazide. The ACE phenotyping included (1) plasma ACE concentration; (2) ACE activity (with 2 substrates: Hip-His-Leu and Z-Phe-His-Leu and calculation of their ratio); (3) detection of ACE inhibitors in patient's blood (indicator of patient compliance) and the degree of ACE inhibition (ie, adherence); and (4) ACE conformation. Enalapril reduced systolic and diastolic blood pressure in most patients; however, 20% of patients were considered nonresponders. Chronic treatment results in 40% increase in serum ACE concentrations, with the exception of 1 patient. There was a trend toward better response to ACEI among patients who had a higher plasma ACE concentration. Due to the fact that "20% of patients do not respond to ACEI by blood pressure drop," the initial blood ACE level could not be a predictor of blood pressure reduction in an individual patient. However, ACE phenotyping provides important information about conformational and kinetic changes in ACE of individual patients, and this could be a reason for resistance to ACE inhibitors in some nonresponders.

  8. Smoking has no impact on survival and it is not associated with ACE gene I/D polymorphism in hemodialysis patients.

    PubMed

    Kiss, István; Kiss, Zoltán; Kerkovits, Lóránt; Paksy, András; Ambrus, Csaba

    2017-01-01

    The relationship between smoking and mortality in patients on hemodialysis is controversial. Earlier studies showed that the insertion/deletion (I/D) polymorphism of the ACE gene might have an effect on mortality. The aim of this study was to test the impact of smoking on survival and whether this association was influenced by ACE gene I/D polymorphism in patients on maintenance hemodialysis. In this prospective, multicenter cohort study we analyzed 709 prevalent patients on maintenance hemodialysis. Patients were allocated into groups based on their smoking habit. Outcome data were collected during the 144-month follow-up period. Outcomes of current smokers and lifelong non-smokers were compared. In order to control for interactions between predictor variables, we also identified 160 matched pairs for further sub-analysis. The vast majority of patients (67%) were non-smokers, followed by current smokers (22.2%) and ex-smokers (9.8%). Smoking had no impact on survival in the matched pair analysis ( p = 0.99). After adjustment for ACE I/D polymorphism and other co-variates, smoking had no effect on survival. Our data suggest that smoking has no impact on survival; neither is it associated with ACE gene I/D polymorphism in hemodialysis patients.

  9. Angiotensin I converting enzyme gene polymorphisms in systemic lupus erythematosus: decreased prevalence of DD genotype in African American patients.

    PubMed

    Tassiulas, I O; Aksentijevich, I; Salmon, J E; Kim, Y; Yarboro, C H; Vaughan, E M; Davis, J C; Scott, D L; Austin, H A; Klippel, J H; Balow, J E; Gourley, M F; Boumpas, D T

    1998-07-01

    The presence of the D (deletion) allele at the angiotensin converting enzyme (ACE) gene has been associated with a) adverse vascular events contributing to early mortality and b) progressive deterioration of renal function in a variety of chronic glomerular diseases. We investigated the potential role of ACE polymorphisms in patients with systemic lupus erythematosus (SLE). Two hundred and sixteen (216) SLE patients (121 Caucasians; 78 African Americans; and 17 other) and 200 normal controls were studied; 134 patients had evidence of renal disease. ACE genotypes were determined by a polymerase chain reaction based assay. The frequency of genotype DD was increased in African American normal controls compared to Caucasians (55% vs. 37%, p = 0.017) and in African American normal controls vs. African American lupus patients (55% vs. 30%, p = 0.008). Trend analysis of the genotype distribution across the three African American groups (renal, non-renal, controls) revealed a trend of increased frequency of I and decreased frequency of D as likelihood of renal disease increases (p = 0.008). No association between any ACE genotype with parameters of renal disease and/or response to therapy was identified. African American patients with lupus have a lower frequency of DD genotype as compared to African American normal controls. Further studies will be necessary to address whether this is due to decreased survival of these patients, a protective effect of DD genotype from developing the disease or a chance sample effect.

  10. Angiotensin-converting enzyme gene polymorphism predicts the time-course of blood pressure response to angiotensin converting enzyme inhibition in the AASK trial

    PubMed Central

    Bhatnagar, Vibha; O’Connor, Daniel T.; Schork, Nicholas J.; Salem, Rany M.; Nievergelt, Caroline M.; Rana, Brinda K.; Smith, Douglas W.; Bakris, George L.; Middleton, John P.; Norris, Keith C.; Wright, Jackson T.; Cheek, Deanna; Hiremath, Leena; Contreras, Gabriel; Appel, Lawrence J.; Lipkowitz, Michael S.

    2009-01-01

    Objective It has yet to be determined whether genotyping at the angiotensin-converting enzyme (ACE) locus is predictive of blood pressure response to an ACE inhibitor. Methods Participants from the African American Study of Kidney Disease and Hypertension trial randomized to the ACE inhibitor ramipril (n = 347) were genotyped at three polymorphisms on ACE, just downstream from the ACE insertion/deletion polymorphism (Ins/Del): G12269A, C17888T, and G20037A. Time to reach target mean arterial pressure (≤ 107 mmHg) was analyzed by genotype and ACE haplotype using Kaplan–Meier survival curves and Cox proportional hazard models. Results Individuals with a homozygous genotype at G12269A responded significantly faster than those with a heterozygous genotype; the adjusted (average number of medications and baseline mean arterial pressure) hazard ratio (homozygous compared to heterozygous genotype) was 1.86 (95% confidence limits 1.32–3.23; P < 0.001 for G12269A genotype). The adjusted hazard ratio for participants with homozygous ACE haplotypes compared to those heterozygous ACE haplotypes was 1.40 (1.13–1.75; P = 0.003 for haplotype). The ACE genotype effects were specific for ACE inhibition (i.e., not seen among those randomized to a calcium channel blocker), and were independent of population stratification. Conclusions African-Americans with a homozygous genotype at G12269A or homozygous ACE haplotypes responded to ramipril significantly faster than those with a heterozygous genotype or heterozygous haplotypes, suggesting that heterosis may be an important determinant of responsiveness to an ACE inhibitor. These associations may be a result of biological activity of this polymorphism, or of linkage disequilibrium with nearby variants such as the ACE Ins/Del, perhaps in the regulation of ACE splicing. PMID:17885551

  11. Genes Encoding Enzymes Involved in Ethanol Metabolism

    PubMed Central

    Hurley, Thomas D.; Edenberg, Howard J.

    2012-01-01

    The effects of beverage alcohol (ethanol) on the body are determined largely by the rate at which it and its main breakdown product, acetaldehyde, are metabolized after consumption. The main metabolic pathway for ethanol involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven different ADHs and three different ALDHs that metabolize ethanol have been identified. The genes encoding these enzymes exist in different variants (i.e., alleles), many of which differ by a single DNA building block (i.e., single nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with altered kinetic properties. For example, certain ADH1B and ADH1C variants that are commonly found in East Asian populations lead to more rapid ethanol breakdown and acetaldehyde accumulation in the body. Because acetaldehyde has harmful effects on the body, people carrying these alleles are less likely to drink and have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced activity results in acetaldehyde buildup and also has a protective effect against alcoholism. In addition to affecting drinking behaviors and risk for alcoholism, ADH and ALDH alleles impact the risk for esophageal cancer. PMID:23134050

  12. Hepatic Xenobiotic Metabolizing Enzyme Gene Expression ...

    EPA Pesticide Factsheets

    BACKGROUND: Differences in responses to environmental chemicals and drugs between life stages are likely due in part to differences in the expression of xenobiotic metabolizing enzymes and transporters (XMETs). No comprehensive analysis of the mRNA expression of XMETs has been carried out through life stages in any species. RESULTS: Using full-genome arrays, the mRNA expression of all XMETs and their regulatory proteins was examined during fetal (gestation day (GD) 19), neonatal (postnatal day (PND) 7), prepubescent (PND32), middle age (12 months), and old age (18 and 24 months) in the C57BL/6J (C57) mouse liver and compared to adults. Fetal and neonatal life stages exhibited dramatic differences in XMET mRNA expression compared to the relatively minor effects of old age. The total number of XMET probe sets that differed from adults was 636, 500, 84, 5, 43, and 102 for GD19, PND7, PND32, 12 months, 18 months and 24 months, respectively. At all life stages except PND32, under-expressed genes outnumbered over-expressed genes. The altered XMETs included those in all of the major metabolic and transport phases including introduction of reactive or polar groups (Phase I), conjugation (Phase II) and excretion (Phase III). In the fetus and neonate, parallel increases in expression were noted in the dioxin receptor, Nrf2 components and their regulated genes while nuclear receptors and regulated genes were generally down-regulated. Suppression of male-specific XMETs w

  13. A Modern Understanding of the Traditional and Nontraditional Biological Functions of Angiotensin-Converting Enzyme

    PubMed Central

    Ong, Frank S.; Blackwell, Wendell-Lamar B.; Shah, Kandarp H.; Giani, Jorge F.; Gonzalez-Villalobos, Romer A.; Shen, Xiao Z.; Fuchs, Sebastien

    2013-01-01

    Angiotensin-converting enzyme (ACE) is a zinc-dependent peptidase responsible for converting angiotensin I into the vasoconstrictor angiotensin II. However, ACE is a relatively nonspecific peptidase that is capable of cleaving a wide range of substrates. Because of this, ACE and its peptide substrates and products affect many physiologic processes, including blood pressure control, hematopoiesis, reproduction, renal development, renal function, and the immune response. The defining feature of ACE is that it is composed of two homologous and independently catalytic domains, the result of an ancient gene duplication, and ACE-like genes are widely distributed in nature. The two ACE catalytic domains contribute to the wide substrate diversity of ACE and, by extension, the physiologic impact of the enzyme. Several studies suggest that the two catalytic domains have different biologic functions. Recently, the X-ray crystal structure of ACE has elucidated some of the structural differences between the two ACE domains. This is important now that ACE domain-specific inhibitors have been synthesized and characterized. Once widely available, these reagents will undoubtedly be powerful tools for probing the physiologic actions of each ACE domain. In turn, this knowledge should allow clinicians to envision new therapies for diseases not currently treated with ACE inhibitors. PMID:23257181

  14. Apolipoproteins B and E, and angiotensin I-converting enzyme (ACE) genetic polymorphisms in Italian women with coronary artery disease (CAD) and their relationships with plasma lipid and apolipoprotein levels.

    PubMed

    Corbo, R M; Vilardo, T; Mantuano, E; Ruggeri, M; Gemma, A T; Scacchi, R

    1997-08-01

    The XbaI, EcoRI and the signal peptide insertion/deletion (I/D) polymorphic sites of APOB gene, the CfoI polymorphic site of apolipoprotein E gene (APOE), and the insertion/deletion polymorphism of angiotensin I-converting enzyme (ACE) gene were studied using polymerase chain reaction (PCR) in 55 postmenopausal women with coronary artery disease (CAD) and in 119 control women of equivalent age. Patients and controls were recruited from the population of Rome, considered representative of Central and Southern Italy. There were no significant differences in allele frequencies between the two groups, though APOB X-, R- and I, APOE*3, and ACE D alleles were slightly more frequent in the cases than in the controls. The patients did not differ from the controls for plasma total cholesterol (TC), HDL-cholesterol, LDL-cholesterol, and apoAI values, while they presented significantly higher levels of triglycerides and apoB, and lower apoE levels. TC, apoE, and apoB quantitative values, adjusted for age, varied significantly among APOB XbaI and APOE genotypes. APOB X-X- genotype was associated in patients with a significantly lower mean TC concentration than the other two genotypes pooled together. APOE 3-2 genotype in the controls had significantly lower TC levels with respect to the other two pooled genotypic classes and higher apoE levels compared to 3-3 and 4-3 genotypes. In the patients, 3-2 genotype had significantly lower apoB levels than the pooled 3-3 and 4-3 class. We conclude that in the Italian women the DNA polymorphisms studied in this work do not seem to be important risk factors for CAD occurrence; that apoE quantitation could be another useful parameter to identify subjects at risk of CAD; and that APOB X- and APOE*2 are the alleles that most influence the interindividual plasma lipid variation among CAD female patients.

  15. Two Bombyx mori acetylcholinesterase genes influence motor control and development in different ways

    USDA-ARS?s Scientific Manuscript database

    Among its other biological roles, acetylcholinesterase (AChE, EC 3.1.1.7), encoded by two ace genes in most insects, catalyses the breakdown of acetylcholine, thereby terminating synaptic transmission. ace1 encodes the synaptic enzyme and ace2 has other essential actions in many insect species, such...

  16. In Vitro Modulation of Renin-Angiotensin System Enzymes by Amaranth (Amaranthus hypochondriacus) Protein-Derived Peptides: Alternative Mechanisms Different from ACE Inhibition.

    PubMed

    Quiroga, Alejandra V; Aphalo, Paula; Nardo, Agustina E; Añón, María C

    2017-08-30

    Among the factors affecting the development of cardiovascular diseases, hypertension is one of the most important. Research done on amaranth proteins has demonstrated their hypotensive capacity in vivo and in vitro; nevertheless, the mechanism underlying this effect remains unclear. The aim of this study was to analyze in vitro the inhibition of peptides derived from an amaranth hydrolysate (AHH) on other RAS enzymes other than ACE. The chymase and renin activities were studied. AHH was not able to inhibit chymase activity, although a dose-response effect was found on renin activity (IC50 0.6 mg/mL). To provide an approach to the renin inhibition mechanism, we analyzed AHH renin inhibition kinetics and performed a structural characterization of the peptides involved in the effect in terms of molecular size and hydrophobicity. Results suggest that amaranth peptides exhibit renin competitive inhibition behavior. Renin inhibition potency was directly related to peptide hydrophobicity. RP-HPLC separation of AHH and subsequent analysis of the peptide sequences showed 6 peptides belonging to 11S globulin (that can be grouped into 3 families) that would be responsible for renin inhibition. These results demonstrate that Amaranthus hypochondriacus seeds are an adequate source of peptides with renin inhibitory properties that could be used in functional food formulations.

  17. ACE I/D Polymorphism in Hypertensive Patients of Kashmiri Population

    PubMed Central

    Sameer, A. Syed; Syeed, Nidda; Tak, Shahid A.; Bashir, Samina; Nissar, Saniya; Siddiqi, Mushtaq A.

    2010-01-01

    Background The angiotensin-converting enzyme (ACE) gene in humans has an insertion-deletion (I/D) polymorphic state in intron 16 on chromosome 17q23. This polymorphism has been widely investigated in different diseases. In this study we aimed to investigate the ACE I/D genotype frequency in hypertensive cases in Kashmiri population. Materials and Methods We designed a case control study, where 52 hypertensive cases were studied for ACE I/D polymorphism against 150 age/sex matched controls taken from general population. The polymorphisms of ACE gene were investigated using polymerase chain reaction for detection of ACE I/D genotype. Fisher’s Chi square test was used for calculation of P value and OR. Results We found the frequency of ACE DD genotype to be 46.15% (24/52), II 23.07% (12/52) and DI 30.77% (16/52) in 52 hypertensive cases. Conclusions The ACE I/D genotype is positively associated with hypertension in our population.

  18. Clinical Relevance of MTHFR, eNOS, ACE, and ApoE Gene Polymorphisms and Serum Vitamin Profile among Malay Patients with Ischemic Stroke.

    PubMed

    Wei, Loo Keat; Au, Anthony; Menon, Saras; Gan, Siew Hua; Griffiths, Lyn R

    2015-09-01

    The purpose of this study was threefold. First, it was to determine the relationship between serum vitamin profiles and ischemic stroke. The second purpose was to investigate the association of methylenetetrahydrofolate reductase (MTHFR), endothelial nitric oxide synthase (eNOS), angiotensin converting enzyme (ACE), and apolipoprotein-E (ApoE) gene polymorphisms with ischemic stroke and further correlate with serum vitamin profiles among ischemic stroke patients. The third purpose of the study was to highlight the interaction of MTHFR and eNOS haplotypes with serum vitamin profiles and ischemic stroke risks. Polymorphisms of these genes were analyzed in age-, sex-, and ethnicity-matched case-controls (n = 594); serum vitamin profiles were determined using immunoassays. The MTHFR 677C>T, 1298A>C, eNOS intron 4a/b, and ApoE polymorphisms were significantly associated with the increased risk of ischemic stroke. Elevated serum homocysteine and vitamin B12 levels were associated with MTHFR 677C>T and eNOS intron 4a/b polymorphisms. The ApoE and eNOS -786T>C polymorphisms were associated with increased serum vitamin B12 levels. However, none of the polymorphisms influenced serum folate levels except for the MTHFR 1298A>C. Different patterns of MTHFR and eNOS haplotypes tend to affect serum vitamin profiles to different degrees, which contribute to either different susceptibility risk or protective effect on ischemic stroke. Overall, increased levels of serum homocysteine and vitamin B12 levels were associated with higher risk of ischemic stroke in the investigated population. The present study suggests that the genotypes and haplotypes of MTHFR 677C>T and eNOS intron 4a/b polymorphisms are potential serum biomarkers in the pathophysiological processes of ischemic stroke, by modulating homocysteine and vitamin B12 levels. Copyright © 2015 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  19. ACE blood test

    MedlinePlus

    ... to help diagnose and monitor a disorder called sarcoidosis . People with sarcoidosis may have their ACE level tested regularly to ... normal ACE level may be a sign of sarcoidosis. ACE levels may rise or fall as sarcoidosis ...

  20. High Incidence of ACE/PAI-1 in Association to a Spectrum of Other Polymorphic Cardiovascular Genes Involving PBMCs Proinflammatory Cytokines in Hypertensive Hypercholesterolemic Patients: Reversibility with a Combination of ACE Inhibitor and Statin

    PubMed Central

    Mouawad, Charbel; Haddad, Katia; Hamoui, Samar; Azar, Albert; Fajloun, Ziad; Makdissy, Nehman

    2015-01-01

    Cardiovascular diseases (CVDs) are significantly high in the Lebanese population with the two most predominant forms being atherosclerosis and venous thrombosis. The purpose of our study was to assess the association of a spectrum of CVD related genes and combined state of hypertension hypercholesterolemia (HH) in unrelated Lebanese. Twelve polymorphisms were studied by multiplex PCR and reverse hybridization of DNA from 171 healthy individuals and 144 HH subjects. Two genes were significantly associated with HH: ACE (OR: 9.20, P<0.0001) and PAI-1 (OR: 2.29, P = 0.007), respectively with the occurrence of the risky alleles “Del” and “4G”. The frequencies of the Del and 4G alleles were found to be 0.98 and 0.90 in the HH group versus 0.84 and 0.79 in the healthy group, respectively. Serum ACE activity and PAI-I increased significantly with Del/Del and 4G/5G genotypes. The co-expression of Del/4G(+/+) was detected in 113 out of 171 (66.0%) controls and 125 out of 144 (86.8%) HH subjects. Del/4G(-/-) was detected in only 6 (3.5%) controls and undetected in the HH group. Three venous thrombosis related genes [FV(Leiden), MTHFR(A1298C) and FXIII(V34L)] were significantly related to the prominence of the co-expression of Del/4G(+/+). A range of 2 to 8 combined polymorphisms co-expressed per subject where 5 mutations were the most detected. In Del/4G(+/+) subjects, peripheral blood mononuclear cells (PBMCs) produced significant elevated levels of IFN-γ and TNF-α contrary to IL-10, and no variations occurred for IL-4. ACE inhibitor (ramipril) in combination with statin (atorvastatin) and not alone reversed significantly the situation. This first report from Lebanon sheds light on an additional genetic predisposition of a complex spectrum of genes involved in CVD and suggests that the most requested gene FVL by physicians may not be sufficient to diagnose eventual future problems that can occur in the cardiovascular system. Subjects expressing the double mutations

  1. ACE/ACE2 Ratio and MMP-9 Activity as Potential Biomarkers in Tuberculous Pleural Effusions

    PubMed Central

    Hsieh, Wen-Yeh; Kuan, Tang-Ching; Cheng, Kun-Shan; Liao, Yan-Chiou; Chen, Mu-Yuan; Lin, Pei-Heng; Hsu, Yuan-Chang; Huang, Chen-Yi; Hsu, Wei-Hua; Yu, Sheng-Yao; Lin, Chih-Sheng

    2012-01-01

    Objective: Pleural effusion is common problem, but the rapid and reliable diagnosis for specific pathogenic effusions are lacking. This study aimed to identify the diagnosis based on clinical variables to differentiate pleural tuberculous exudates from other pleural effusions. We also investigated the role of renin-angiotensin system (RAS) and matrix metalloproteinase (MMPs) in the pathogenesis of pleural exudates. Experimental design: The major components in RAS and extracellular matrix metabolism, including angiotensin converting enzyme (ACE), ACE2, MMP-2 and MMP-9 activities, were measured and compared in the patients with transudative (n = 45) and exudative (n = 80) effusions. The exudative effusions were come from the patients with tuberculosis (n = 20), pneumonia (n = 32), and adenocarcinoma (n = 28). Results: Increased ACE and equivalent ACE2 activities, resulting in a significantly increased ACE/ACE2 ratio in exudates, were detected compared to these values in transudates. MMP-9 activity in exudates was significantly higher than that in transudates. The significant correlation between ACE and ACE2 activity that was found in transudates was not found in exudates. Advanced analyses showed significantly increased ACE and MMP-9 activities, and decreased ACE2 activity in tuberculous pleural effusions compared with those in pneumonia and adenocarcinoma effusions. The results indicate that increased ACE and MMP-9 activities found in the exudates were mainly contributed from a higher level of both enzyme activities in the tuberculous pleural effusions. Conclusion: Interplay between ACE and ACE2, essential functions in the RAS, and abnormal regulation of MMP-9 probably play a pivotal role in the development of exudative effusions. Moreover, the ACE/ACE2 ratio combined with MMP-9 activity in pleural fluid may be potential biomarkers for diagnosing tuberculous pleurisy. PMID:23091417

  2. Angiotensin converting enzyme 2 abrogates bleomycin-induced lung injury.

    PubMed

    Rey-Parra, G J; Vadivel, A; Coltan, L; Hall, A; Eaton, F; Schuster, M; Loibner, H; Penninger, J M; Kassiri, Z; Oudit, G Y; Thébaud, B

    2012-06-01

    Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin-angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice-male (ACE2(-/y)) and female (ACE2(-/-))-and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2(-/y) BLM injured mice exhibited poorer exercise capacity, worse lung function and exacerbated lung fibrosis and collagen deposition compared with WT. These changes were associated with increased expression of the profibrotic genes α-smooth muscle actin (α-SMA) and Transforming Growth Factor ß1. Compared with ACE2(-/y) exposed to BLM, ACE2(-/-) exhibited better lung function and architecture and decreased collagen deposition. Treatment with intraperitoneal recombinant human (rh) ACE2 (2 mg/kg) for 21 days improved survival, exercise capacity, and lung function and decreased lung inflammation and fibrosis in male BLM-WT mice. Female BLM WT mice had mild fibrosis and displayed a possible compensatory upregulation of the AT2 receptor. We conclude that ACE2 gene deletion worsens BLM-induced lung injury and more so in males than females. Conversely, ACE2 protects against BLM-induced fibrosis. rhACE2 may have therapeutic potential to attenuate respiratory morbidity in ALI/ARDS.

  3. ACE insert/delete polymorphism and atherosclerosis.

    PubMed

    Scheer, W Douglas; Boudreau, Donald A; Hixson, James E; McGill, Henry C; Newman, William P; Tracy, Richard E; Zieske, Arthur W; Strong, Jack P

    2005-02-01

    We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

  4. ACE2 alterations in kidney disease

    PubMed Central

    Soler, María José; Wysocki, Jan; Batlle, Daniel

    2013-01-01

    Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase that degrades angiotensin (Ang) II to Ang-(1–7). ACE2 is highly expressed within the kidneys, it is largely localized in tubular epithelial cells and less prominently in glomerular epithelial cells and in the renal vasculature. ACE2 activity has been shown to be altered in diabetic kidney disease, hypertensive renal disease and in different models of kidney injury. There is often a dissociation between tubular and glomerular ACE2 expression, particularly in diabetic kidney disease where ACE2 expression is increased at the tubular level but decreased at the glomerular level. In this review, we will discuss alterations in circulating and renal ACE2 recently described in different renal pathologies and disease models as well as their possible significance. PMID:23956234

  5. Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression.

    PubMed

    Ancelin, M L; Carrière, I; Scali, J; Ritchie, K; Chaudieu, I; Ryan, J

    2013-11-05

    Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis, which shows hyperactivity in depressed patients. ACE could thus be a promising candidate gene for late-life depression but this has not been examined previously. Depression was assessed in 1005 persons aged at least 65 years, at baseline and over the 10-year follow-up. A clinical level of depression (DEP) was defined as having a score of > or =16 on the Centre for Epidemiology Studies-Depression scale or a diagnosis of current major depression based on the Mini International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) in the ACE gene were genotyped and diurnal cortisol secretion, as an index of HPA axis activity, was measured. Multivariable analyses were adjusted for socio-demographic and vascular factors, cognitive impairment, and apolipoprotein E. Strong significant associations were found between all seven SNPs and DEP and, in particular, first-onset DEP in persons without a past history of depression (P-values ranging from 0.005 to 0.0004). These associations remained significant after correction for multiple testing. The genotypes that were associated with an increased risk of DEP were also significantly associated with an increase in cortisol secretion under stress conditions. Variants of the ACE gene influence cortisol secretion and appear as susceptibility factors for late-life depression in the elderly population. Whether this could represent a common pathophysiological mechanism linking HPA axis and late-life depression remains to be explored.

  6. Effect of angiotensin I-converting enzyme and α-actinin-3 gene polymorphisms on sport performance.

    PubMed

    Gunel, Tuba; Gumusoglu, Ece; Hosseini, Mohammad Kazem; Yilmazyildirim, Eda; Dolekcap, Ismail; Aydinli, Kilic

    2014-04-01

    Genetic polymorphism is considered to be associated with human physical performance. The angiotensin I-converting enzyme insertion/deletion (ACE I/D) and the α-actinin-3 gene (ACTN3) R577X polymorphisms have been widely investigated for such associations, and functional ACE I/D and ACTN3 R577X polymorphisms have been associated with sprinter performance. The aim of this study was to determine the effect of these polymorphisms on sport performance among 37 elite athletes and 37 healthy controls. The ACE II genotype was identified in 32.43% of the control group and 8.11% of elite athletes, the DD genotype in 37.84% of the control group and 51.35% of the elite athletes, and the ID genotype in 29.73% of the control group and 40.54% of the elite athletes. With regard to the ACTN3 gene, the XX genotype, which confers an advantage for endurance activities, was identified in 10.81% of the control group and 35.14% of the elite athletes. The XX genotype was observed more frequently than the RR genotype (advantageous for sprinting), which was identified in 2.70% of the control group and 10.81% of elite athletes. The RX genotype (observed in 86.48% of the control group and in 54.05% of the elite athletes) was the most common genotype of the individuals in the present study. The study showed that ACTN3 and ACE gene polymorphisms have an effect on muscle power; however, larger studies are required.

  7. MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly

    ERIC Educational Resources Information Center

    Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj

    2009-01-01

    Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…

  8. MTHFR and ACE Gene Polymorphisms and Risk of Vascular and Degenerative Dementias in the Elderly

    ERIC Educational Resources Information Center

    Pandey, Pratima; Pradhan, Sunil; Modi, Dinesh Raj; Mittal, Balraj

    2009-01-01

    Focal lacunar infarctions due to cerebral small vessel atherosclerosis or single/multiple large cortical infarcts lead to vascular dementia, and different genes and environmental factors have been implicated in causation or aggravation of the disease. Previous reports suggest that some of the risk factors may be common to both vascular as well as…

  9. Is there an ACE ID - ACTN3 R577X polymorphisms interaction that influences sprint performance?

    PubMed

    Eynon, N; Alves, A J; Yamin, C; Sagiv, M; Duarte, J A; Oliveira, J; Ayalon, M; Goldhammer, E; Sagiv, M; Meckel, Y

    2009-12-01

    Functional R577X (rs.1815739) and ID (rs.5186) polymorphisms in the alpha-actinin-3 ( ACTN3) and the angiotensin converting enzyme (ACE) genes, respectively, have been associated with sprint performance. The aim of this study was to determine their effect on sprint performance among 81 Israeli sprinters and 240 healthy controls. Results revealed that the ACE II genotype+ ACTN3 R allele (P=0.003 for sprinters vs. controls), and the ACTN3 RR genotype +ACE I allele (P=0.001 for sprinters vs. controls) might be the genotype for sprinters. In the whole cohort the probability of ACTN3 RR genotype+ ACE I allele being a sprinter (odds ratio 2.67, 95% confidence interval 1.45-4.93) and of ACE II genotype+ ACTN3 R allele being a sprinter (odds ratio 3.57, 95% confidence interval 1.78-7.15) was significantly higher than that in the controls. In conclusion, the above data suggest that ACE ID/ ACTN3 R577X genotype combination is associated with sprint ability. However, ACE ID/ ACTN3 R577X genotype combination is not related to the level of performance.

  10. ACE--Some Issues.

    ERIC Educational Resources Information Center

    Campbell, Annie, Ed.; Curtin, Penelope, Ed.

    This publication contains four papers that identify issues within the adult and community education (ACE) sector. "Overview" (Annie Campbell, Peter Thomson) considers what defines ACE; who offers ACE programs; who participates in ACE programs and who does not participate; what are the barriers to participation; who is responsible for…

  11. Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure

    PubMed Central

    Duque, Gustavo Salgado; da Silva, Dayse Aparecida; de Albuquerque, Felipe Neves; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; de Albuquerque, Denilson Campos

    2016-01-01

    Background Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. Objectives To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Methods Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. Results The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. Conclusions More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. PMID:27812677

  12. Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population

    PubMed Central

    Al-Saikhan, Fahad I.; Abd-Elaziz, Mohamed A.; Ashour, Rehab H.

    2017-01-01

    The link between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the prevalence of type 2 diabetes mellitus (T2DM) developing in the Saudi Arabian population remains controversial. The aim of the present study was to evaluate the association between the ACE I/D gene polymorphism and the risk of developing T2DM and hypertension (HTN) in Saudi Arabian individuals. A total of 220 individuals consisting of 48 control subjects, 70 T2DM, 48 HTN, and 54 T2DM with HTN patients were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of the DD genotypes was conducted with an insertion-specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene was 6.8, 42.6 and 48.6% in T2DM patients, 4.2, 50 and 45.8% in HTN patients, 5.6, 55.5 and 38.9% in T2DM patients with HTN and 58.3, 37.5 and 4.2% in control subjects, respectively. The frequency for the D allele was 70% in T2DM patients, 70.8% in HTN patients and 66.7% in T2DM patients with HTN as compared with 22.9% in the control subjects. The genotype and allele frequency of the ACE gene polymorphism varied significantly (P<0.05) in the patients when compared with the control subjects. The current study demonstrated that the ID/DD genotype and the D allele of the ACE gene I/D polymorphism were strongly associated with the risk of T2DM and HTN developing in a Saudi Arabian population. PMID:28685061

  13. Association between risk of type 2 diabetes mellitus and angiotensin-converting enzyme insertion/deletion gene polymorphisms in a Saudi Arabian population.

    PubMed

    Al-Saikhan, Fahad I; Abd-Elaziz, Mohamed A; Ashour, Rehab H

    2017-07-01

    The link between the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and the prevalence of type 2 diabetes mellitus (T2DM) developing in the Saudi Arabian population remains controversial. The aim of the present study was to evaluate the association between the ACE I/D gene polymorphism and the risk of developing T2DM and hypertension (HTN) in Saudi Arabian individuals. A total of 220 individuals consisting of 48 control subjects, 70 T2DM, 48 HTN, and 54 T2DM with HTN patients were recruited. Genotyping was performed by polymerase chain reaction initially and mistyping of the DD genotypes was conducted with an insertion-specific primer. The genotyping frequency for the II, ID and DD polymorphism of the ACE gene was 6.8, 42.6 and 48.6% in T2DM patients, 4.2, 50 and 45.8% in HTN patients, 5.6, 55.5 and 38.9% in T2DM patients with HTN and 58.3, 37.5 and 4.2% in control subjects, respectively. The frequency for the D allele was 70% in T2DM patients, 70.8% in HTN patients and 66.7% in T2DM patients with HTN as compared with 22.9% in the control subjects. The genotype and allele frequency of the ACE gene polymorphism varied significantly (P<0.05) in the patients when compared with the control subjects. The current study demonstrated that the ID/DD genotype and the D allele of the ACE gene I/D polymorphism were strongly associated with the risk of T2DM and HTN developing in a Saudi Arabian population.

  14. Characterization of the mammalian DNA polymerase gene(s) and enzyme(s). Annual progress report

    SciTech Connect

    Mishra, N.C.

    1994-01-01

    Consistent with the long term goal of our research to understand the nature of the key enzymes in eukaryotic DNA replication we have characterized the properties of the wild type DNA polymerases of the {alpha}-family and their mutants. We have also provided evidence for the role of aphidicolin in the elongation process of the in vivo DNA replication in eukaryotic cells. We also developed a technology for planned prep from a large numbers of clones for direct screening by size or restriction digestion in order to facilitate our goals to clone the DNA polymerase gene.

  15. A novel angiotensin-І converting enzyme (ACE) inhibitory peptide from gastrointestinal protease hydrolysate of silkworm pupa (Bombyx mori) protein: Biochemical characterization and molecular docking study.

    PubMed

    Wu, Qiongying; Jia, Junqiang; Yan, Hui; Du, Jinjuan; Gui, Zhongzheng

    2015-06-01

    Silkworm pupa (Bombyx mori) protein was hydrolyzed using gastrointestinal endopeptidases (pepsin, trypsin and α-chymotrypsin). Then, the hydrolysate was purified sequentially by ultrafiltration, gel filtration chromatography and RP-HPLC. A novel ACE inhibitory peptide, Ala-Ser-Leu, with the IC50 value of 102.15μM, was identified by IT-MS/MS. This is the first report of Ala-Ser-Leu from natural protein. Lineweaver-Burk plots suggest that the peptide is a competitive inhibitor against ACE. The molecular docking studies revealed that the ACE inhibition of Ala-Ser-Leu is mainly attributed to forming very strong hydrogen bonds with the S1 pocket (Ala354) and the S2 pocket (Gln281 and His353). The results indicate that silkworm pupa (B. mori) protein or its gastrointestinal protease hydrolysate could be used as a functional ingredient in auxiliary therapeutic foods against hypertension.

  16. Angiotensin-converting enzyme insertion/deletion gene polymorphism in Egyptian children with systemic lupus erythematosus: a possible relation to proliferative nephritis.

    PubMed

    Hammad, A; Yahia, S; Laimon, W; Hamed, S M; Shouma, A; Shalaby, N M; Abdel-Hady, D; Ghanem, R; El-Farahaty, R M; El-Bassiony, S R; Hammad, E M

    2017-06-01

    Introduction Angiotensin-converting enzyme (ACE) is crucial in the pathogenesis of systemic lupus erythematosus through angiotensin II which regulates vascular tone and endothelial functions. Objectives To study the frequency of ACE insertion/deletion (I/D) gene polymorphism in Egyptian children with systemic lupus erythematosus and its possible relation to the renal pathology in cases with lupus nephritis. Subjects and methods The frequency of ACE gene insertion/deletion polymorphism genotypes was determined in 78 Egyptian children with systemic lupus erythematosus and compared to a matched group of 140 healthy controls using polymerase chain reaction. Results The DD genotype of the ACE gene was higher in systemic lupus erythematosus patients when compared to controls ( P<0.0001; odds ratio (OR) 2.4; 95% confidence interval (CI) 1.7-3.3) and the D allele was more frequent than the I allele in systemic lupus erythematosus patients in comparison to controls ( P < 0.0001; OR = 2.2; 95% CI = (1.6-3.1). In the lupus nephritis group, the DD genotype was significantly higher in those with proliferative lupus nephritis when compared to those with non-proliferative lupus nephritis ( P = 0.02; OR = 1.45; 95% CI = 1.4-1.6). Also, patients with proliferative lupus nephritis showed a higher frequency of the D allele ( P < 0.001; OR = 1.98; 95% CI = 1.3-2.9). Conclusion The D allele and DD genotype of the ACE gene appear to be a risk factor for the susceptibility of systemic lupus erythematosus and occurrence of proliferative nephritis in Egyptian children.

  17. ACE2 Therapy Using Adeno-associated Viral Vector Inhibits Liver Fibrosis in Mice

    PubMed Central

    Mak, Kai Y; Chin, Ruth; Cunningham, Sharon C; Habib, Miriam R; Torresi, Joseph; Sharland, Alexandra F; Alexander, Ian E; Angus, Peter W; Herath, Chandana B

    2015-01-01

    Angiotensin converting enzyme 2 (ACE2) which breaks down profibrotic peptide angiotensin II to antifibrotic peptide angiotensin-(1–7) is a potential therapeutic target in liver fibrosis. We therefore investigated the long-term therapeutic effect of recombinant ACE2 using a liver-specific adeno-associated viral genome 2 serotype 8 vector (rAAV2/8-ACE2) with a liver-specific promoter in three murine models of chronic liver disease, including carbon tetrachloride-induced toxic injury, bile duct ligation-induced cholestatic injury, and methionine- and choline-deficient diet-induced steatotic injury. A single injection of rAAV2/8-ACE2 was administered after liver disease has established. Hepatic fibrosis, gene and protein expression, and the mechanisms that rAAV2/8-ACE2 therapy associated reduction in liver fibrosis were analyzed. Compared with control group, rAAV2/8-ACE2 therapy produced rapid and sustained upregulation of hepatic ACE2, resulting in a profound reduction in fibrosis and profibrotic markers in all diseased models. These changes were accompanied by reduction in hepatic angiotensin II levels with concomitant increases in hepatic angiotensin-(1–7) levels, resulting in significant reductions of NADPH oxidase assembly, oxidative stress and ERK1/2 and p38 phosphorylation. Moreover, rAAV2/8-ACE2 therapy normalized increased intrahepatic vascular tone in fibrotic livers. We conclude that rAAV2/8-ACE2 is an effective liver-targeted, long-term therapy for liver fibrosis and its complications without producing unwanted systemic effects. PMID:25997428

  18. Regulation of steady-state beta-amyloid levels in the brain by neprilysin and endothelin-converting enzyme but not angiotensin-converting enzyme.

    PubMed

    Eckman, Elizabeth A; Adams, Stephanie K; Troendle, Frederick J; Stodola, Becky A; Kahn, Murad A; Fauq, Abdul H; Xiao, Hong D; Bernstein, Kenneth E; Eckman, Christopher B

    2006-10-13

    The deposition of beta-amyloid in the brain is a pathological hallmark of Alzheimer disease (AD). Normally, the accumulation of beta-amyloid is prevented in part by the activities of several degradative enzymes, including the endothelin-converting enzymes, neprilysin, insulin-degrading enzyme, and plasmin. Recent reports indicate that another metalloprotease, angiotensin-converting enzyme (ACE), can degrade beta-amyloid in vitro and in cellular overexpression experiments. In addition, ACE gene variants are linked to AD risk in several populations. Angiotensin-converting enzyme, neprilysin and endothelin-converting enzyme function as vasopeptidases and are the targets of drugs designed to treat cardiovascular disorders, and ACE inhibitors are commonly prescribed. We investigated the potential physiological role of ACE in regulating endogenous brain beta-amyloid levels for two reasons: first, to determine whether beta-amyloid degradation might be the mechanism by which ACE is associated with AD, and second, to determine whether ACE inhibitor drugs might block beta-amyloid degradation in the brain and potentially increase the risk for AD. We analyzed beta-amyloid accumulation in brains from ACE-deficient mice and in mice treated with ACE inhibitors and found that ACE deficiency did not alter steady-state beta-amyloid concentration. In contrast, beta-amyloid levels are significantly elevated in endothelin-converting enzyme and neprilysin knock-out mice, and inhibitors of these enzymes cause a rapid increase in beta-amyloid concentration in the brain. The results of these studies do not support a physiological role for ACE in the degradation of beta-amyloid in the brain but confirm roles for endothelin-converting enzyme and neprilysin and indicate that reductions in these enzymes result in additive increases in brain amyloid beta-peptide levels.

  19. Polymorphisms of the insertion / deletion ACE and M235T AGT genes and hypertension: surprising new findings and meta-analysis of data.

    PubMed

    Mondry, Adrian; Loh, Marie; Liu, Pengbo; Zhu, Ai-Ling; Nagel, Mato

    2005-01-11

    Essential hypertension is a common, polygenic, complex disorder resulting from interaction of several genes with each other and with environmental factors such as obesity, dietary salt intake, and alcohol consumption. Since the underlying genetic pathways remain elusive, currently most studies focus on the genes coding for proteins that regulate blood pressure as their physiological role makes them prime suspects. The present study examines how polymorphisms of the insertion/deletion (I/D) ACE and M235T AGT genes account for presence and severity of hypertension, and embeds the data in a meta-analysis of relevant studies. The I/D polymorphisms of the ACE and M235T polymorphisms of the AGT genes were determined by RFLP (restriction fragment length polymorphism) and restriction analysis in 638 hypertensive patients and 720 normotensive local blood donors in Weisswasser, Germany. Severity of hypertension was estimated by the number of antihypertensive drugs used. No difference was observed in the allele frequencies and genotype distributions of ACE gene polymorphisms between the two groups, whereas AGT TT homozygotes were more frequent in controls (4.6% vs. 2.7%, P = .08). This became significant (p = 0.035) in women only. AGT TT genotype was associated with a 48% decrease in the risk of having hypertension (odds ratio: 0.52; 95% CI, 0.28 to 0.96), and this risk decreased more significantly in women (odds ratio: 0.28; 95% CI, 0.1 to 0.78). The meta-analysis showed a pooled odds ratio for hypertension of 1.21 (TT vs. MM, 95% CI: 1.11 to 1.32) in Caucasians. No correlation was found between severity of hypertension and a specific genotype. The ACE I/D polymorphism does not contribute to the presence and severity of essential hypertension, while the AGT M235T TT genotype confers a significantly decreased risk for the development of hypertension in the population studied here. This contrasts to the findings of meta-analyses, whereby the T allele is associated with

  20. Effect of combined ultrasonic and alkali pretreatment on enzymatic preparation of angiotensin converting enzyme (ACE) inhibitory peptides from native collagenous materials.

    PubMed

    Zhang, Yuhao; Ma, Liang; Cai, Luyun; Liu, Yi; Li, Jianrong

    2017-05-01

    The combined effect of ultrasonic and alkali pretreatment for the hydrolysis of native collagenous materials and release of ACE inhibitory peptides was investigated. The ultrasonic and alkali pretreatment of pig skin could accelerate the release of the ACE inhibitory peptides from the triple helix of collagen in early stages of hydrolysis. Furthermore, the pretreatment could also accelerate collapse of the triple helix and release more ACE inhibitory peptides during hydrolysis than collagen samples left untreated. Compared to untreated and alkali pretreated samples, the ultrasonic and alkali pretreatment could decrease the thermostability of pig skin significantly (P<0.05) because the ultrasonic and alkali pretreatment could weaken hydrogen bonds and break parts of covalent bonds in collagen, leading to damage of the triple helical structure in collagen. Therefore, the ultrasonic and alkali pretreatment could damage the triple helical structure of collagen in native collagenous materials and expose more inner sites for subsequent hydrolysis, and it could be a potential way to prepare ACE inhibitory peptides effectively from collagen-rich raw material.

  1. An SNP within the Angiotensin-Converting Enzyme Distinguishes between Sprint and Distance Performing Alaskan Sled Dogs in a Candidate Gene Analysis

    PubMed Central

    Huson, Heather J.; Byers, Alexandra M.; Runstadler, Jonathan

    2011-01-01

    The Alaskan sled dog offers a unique mechanism for studying the genetics of elite athletic performance. They are a group of mixed breed dogs, comprised of multiple common breeds, and a unique breed entity seen only as a part of the sled dog mix. Alaskan sled dogs are divided into 2 primary groups as determined by their racing skills. Distance dogs are capable of running over 1000 miles in 10 days, whereas sprint dogs run much shorter distances, approximately 30 miles, but in faster times, that is, 18–25 mph. Finding the genes that distinguish these 2 types of performers is likely to illuminate genetic contributors to human athletic performance. In this study, we tested for association between polymorphisms in 2 candidate genes; angiotensin-converting enzyme (ACE) and myostatin (MSTN) and enhanced speed and endurance performance in 174 Alaskan sled dogs. We observed 81 novel genetic variants within the ACE gene and 4 within the MSTN gene, including a polymorphism within the ACE gene that significantly (P value 2.38 × 10−5) distinguished the sprint versus distance populations. PMID:21846742

  2. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case–control study

    PubMed Central

    Bahramali, Ehsan; Rajabi, Mona; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

    2016-01-01

    Objectives To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Design Case control study. Setting An Iranian referral university hospital. Participants 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. Results The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. Conclusions In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. PMID:26861937

  3. Tissue-Specific Expression of Transgenic Secreted ACE in Vasculature Can Restore Normal Kidney Functions, but Not Blood Pressure, of Ace-/- Mice

    PubMed Central

    Chattopadhyay, Saurabh; Kessler, Sean P.; Colucci, Juliana Almada; Yamashita, Michifumi; Senanayake, Preenie deS; Sen, Ganes C.

    2014-01-01

    Angiotensin-converting enzyme (ACE) regulates normal blood pressure and fluid homeostasis through its action in the renin-angiotensin-system (RAS). Ace-/- mice are smaller in size, have low blood pressure and defective kidney structure and functions. All of these defects are cured by transgenic expression of somatic ACE (sACE) in vascular endothelial cells of Ace-/- mice. sACE is expressed on the surface of vascular endothelial cells and undergoes a natural cleavage secretion process to generate a soluble form in the body fluids. Both the tissue-bound and the soluble forms of ACE are enzymatically active, and generate the vasoactive octapeptide Angiotensin II (Ang II) with equal efficiency. To assess the relative physiological roles of the secreted and the cell-bound forms of ACE, we expressed, in the vascular endothelial cells of Ace-/- mice, the ectodomain of sACE, which corresponded to only the secreted form of ACE. Our results demonstrated that the secreted form of ACE could normalize kidney functions and RAS integrity, growth and development of Ace-/- mice, but not their blood pressure. This study clearly demonstrates that the secreted form of ACE cannot replace the tissue-bound ACE for maintaining normal blood pressure; a suitable balance between the tissue-bound and the soluble forms of ACE is essential for maintaining all physiological functions of ACE. PMID:24475296

  4. Angiotensin-converting enzyme gene polymorphism, left ventricular remodeling, and exercise capacity in strength-trained athletes.

    PubMed

    Kasikcioglu, Erdem; Kayserilioglu, Abidin; Ciloglu, Figen; Akhan, Hulya; Oflaz, Huseyin; Yildiz, Safinaz; Peker, Ismail

    2004-11-01

    The mechanisms that regulate the development of human physiological cardiac hypertrophy remain poorly understood. The renin-angiotensin system, which is modulated by genetic polymorphism, plays an important role in the regulation of vascular tone and myocardial hypertrophy. Although a few studies have analyzed the association of angiotensin-converting enzyme (ACE) polymorphism and left ventricular (LV) hypertrophy in isotonic exercise-trained subjects who developed eccentric cardiac hypertrophy, there has been no research done in power athletes who developed concentric cardiac hypertrophy. We have hypothesized that ACE genotypic modulation characteristics may affect LV mass in power athletes. This study included 29 elite Caucasian wrestlers (mean age, 22.6 years) and 51 age-matched sedentary subjects. According to the absence or presence of the insertion segment in the polymerase chain reaction (PCR) product, the subjects were classified as homozygous deletion-deletion (DD), insertion-insertion (II), or heterozygous insertion-deletion (ID). The association of LV hypertrophy with ACE gene insertion/deletion (I/D) polymorphism was analyzed. Left ventricular mass and index were determined by echocardiography. Angiotensin-converting enzyme genotyping was performed on peripheral leukocytes using the polymerase chain reaction technique. The study and control group subjects were similar in height and weight. Left ventricular hypertrophy in the athletes was more apparent than in the controls. Angiotensin-converting enzyme genotype II frequency was 17.2% (5) in the athletes, 17.6% (9) in the controls; ID frequency was 51.7% (15) in the athletes, 56.8% (29) in the controls; and the DD frequency was 31% (9) in the athletes and 25.4% (13) in the controls. Left ventricular mass and mass index were found to be higher in genotype DD (126.2 +/- 2.9g/m2) than genotype II (85.5 +/- 4.0g/m2) or genotype ID (110.1 +/- 2.3g/m2) in the athletes (P < 0.001). Furthermore, maximal oxygen

  5. Estimation of the relationship between the polymorphisms of selected genes: ACE, AGTR1, TGFβ1 and GNB3 with the occurrence of primary vesicoureteral reflux.

    PubMed

    Życzkowski, Marcin; Żywiec, Joanna; Nowakowski, Krzysztof; Paradysz, Andrzej; Grzeszczak, Władyslaw; Gumprecht, Janusz

    2017-03-01

    Etiopathogenesis of VUR is composite and not fully understood. Many data indicate the importance of genetic predisposition. The aim of this study was to establish the relationship of selected polymorphisms: 14094 polymorphism of the ACE, polymorphism rs1800469 of TGFβ-1, rs5443 gene polymorphism of the GNB3 and receptor gene polymorphism rs5186 type 1 AGTR1 with the occurrence of the primary vesicoureteral reflux. The study included 190 children: 90 with the primary VUR confirmed with the voiding cystourethrogram and excluded secondary VUR and a control group of 100 children without a history of the diseases of the genitourinary tract. The study was planned in the scheme: "tested case versus control." Genomic DNA was isolated from the leukocytes of peripheral blood samples. The results were statistically analyzed in the Statistica 10 using χ (2) test and analysis of the variance Anova. Any of the four studied polymorphisms showed no difference in the distribution of genotypes between patients with primary vesicoureteral reflux and the control group. In patients with VUR and TT genotype polymorphism rs5443 GNB3 gene, the glomerular filtration rate was significantly higher than in patients with genotype CC or CT. (1) No relationship was found between the studied polymorphisms (14094 ACE gene, rs1800469 gene TGFβ1, GNB3 gene rs5443, rs5186 AGTR1 gene) and the occurrence of primary vesicoureteral reflux. (2) TT genotype polymorphism rs5443 GNB3 gene may be a protective factor for the improved renal function in patients with primary vesicoureteral reflux in patients with genotype CC or CT.

  6. Comprehensive Database Service : ACE

    NASA Astrophysics Data System (ADS)

    Hiroki, Morio; Abe, Tetsuya

    The Data base, ACE commercialized by Chunichi Shimbun in Feb. 1986, aims at covering not only newspaper articles but also the other information which composes different data bases. This paper introduces newspaper articles, new material information and character information which are included in ACE. The content of ACE, how to use the online service, and future subjects are described.

  7. Association between angiotensin converting enzyme gene insertion/deletion polymorphism and renal scar risk in children vesicoureteral reflex: a reappraise meta-analysis

    PubMed Central

    Ai, Jin-Wei; Zeng, Xian-Tao; Liu, Ying; Fu, Yu; Liu, Tong-Zu; Pei, Bin

    2016-01-01

    Vesicoureteral reflex(VUR) is a common disease in children. Some studies indicated that the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism associated with the renal scar in VUR, but not all researchers agreed with it. To clarify the effect of ACE I/D polymorphism on renal scar risk in children with VUR, we performed the present meta-analysis. PubMed, CNKI, CBM, and Embase databases were searched for studies that examined the relationship between ACE I/D polymorphism and renal scar risk in children with VUR. The Stata 12.0 software was used for statistical analyses. 11 case-control studies with 1,032 VUR patients were analyzed. The results showed that the DD genotype and D allele were associated with renal scar risk in overall VUR patients, DD vs. DI + II: OR = 1.61, 95% CI = 1.04–2.49, P = 0.03; DD vs. II: OR = 1.78, 95% CI = 1.20–2.65, P < 0.01; D vs. I: OR = 1.38, 95% CI = 1.02–1.86, P = 0.04. Similar results were revealed in Turks, but not in Caucasians and Asians. Our meta-analysis indicated that the ACE DD genotype may increase the risk of renal scar in children with VUR. PMID:27506878

  8. Implications of the angiotensin converting enzyme gene insertion/deletion polymorphism in health and disease: a snapshot review

    PubMed Central

    Gard, Paul R

    2010-01-01

    This review considers the 250+ papers concerning the association of the angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism (rs1799752) and various disease conditions published in 2009. The deletion allele occurs in approximately 55% of the population and is associated with increased activity of the ACE enzyme. It might be predicted that the D allele, therefore, might be associated with pathologies involving increased activity of the renin-angiotensin system. The D allele was seen to be associated with an increased risk of hypertension, pre-eclampsia, heart failure, cerebral infarct, diabetic nephropathy, encephalopathy, asthma, severe hypoglycaemia in diabetes, gastric cancer (in Caucasians) and poor prognosis following kidney transplant. On the positive side, the D allele appears to offer protection against schizophrenia and chronic periodontitis and confers greater up-per-body strength in old age. The I allele, meanwhile, offers improved endurance/athletic performance and aerobic capacity as determined by lung function tests, although it does increase the risk of oral squamous cell carcinoma and obstructive sleep apnoea in hypertensives. PMID:21537387

  9. The ACE Gene Is Associated with Late-Life Major Depression and Age at Dementia Onset in a Population-Based Cohort.

    PubMed

    Zettergren, Anna; Kern, Silke; Gustafson, Deborah; Gudmundsson, Pia; Sigström, Robert; Östling, Svante; Eriksson, Elias; Zetterberg, Henrik; Blennow, Kaj; Skoog, Ingmar

    2017-02-01

    Depression and dementia in the elderly have been suggested to share similar risk factors and pathogenetic background, and recently the authors reported that the APOEɛ4 allele is a risk factor for both disorders in the general population. The aim of the present study was to examine the influence of the well-known polymorphisms rs1799752 in the angiotensin-converting enzyme (ACE) and rs5186 in the angiotensin receptor II type 1 (AGTR1) on late-life depression and dementia in a population-based Swedish cohort of older individuals followed over 12 years. In 2000-2001, 900 individuals underwent neuropsychiatric and neuropsychological examinations. Follow-up evaluations were performed in 2005-2006 and 2009-2010, and register data on dementia to 2012 were included. Cross-sectional associations between genotypes/alleles and depression and dementia at baseline and between genotypes/alleles and depression on at least one occasion during the study period and dementia onset to 2012 were investigated. As previously found for rs1799752 in ACE, rs5186 in AGTR1 was associated with dementia at baseline (OR: 3.25 [CI: 1.42-7.06], z = 2.90, p = 0.004). These associations became substantially weaker, or disappeared, when dementia onset to 2012 was included. For rs1799752 this could be explained by a significant association with age at onset (mean: 79.5 [SD: 6.45] years for risk-genotype carriers and 81.7 [SD: 7.12] years for carriers of other genotypes, b = -2.43, t = -2.38, df = 192, p = 0.02). When individuals with major depression on at least one occasion were analyzed, a significant association (OR: 2.14 [95% CI: 1.13-4.20], z = 2.28, p = 0.02), remaining after exclusion of dementia, with rs1799752 in ACE was found. In this population-based sample of older individuals, genetic variations in ACE seem to be important both for late-life major depression and dementia. Copyright © 2017 American Association for Geriatric Psychiatry. Published by

  10. Polymorphisms in angiotensin II type 1 receptor and angiotensin I-converting enzyme genes and breast cancer risk among Chinese women in Singapore.

    PubMed

    Koh, Woon-Puay; Yuan, Jian-Min; Van Den Berg, David; Lee, Hin-Peng; Yu, Mimi C

    2005-02-01

    Angiotensin II is converted from its precursor by angiotensin I-converting enzyme (ACE) and has been shown to mediate growth in breast cancer cell lines via ligand-induced activity through the angiotensin II type 1 receptor (AGTR1). Earlier we showed that women with the low activity genotype of the ACE gene have a statistically significantly ( approximately 50%) reduced breast cancer risk compared with those possessing the high activity ACE genotype. To further test the hypothesis that angiotensin II participates in breast carcinogenesis through AGTR1, we examined genetic polymorphisms in the 5'-region of the AGTR1 gene (A-168G, C-535T and T-825A) in relation to risk of breast cancer in 258 breast cancer cases and 670 female controls within the Singapore Chinese Health Study. Relative to the homozygotes, individual genotypes with one or two copies of the respective allelic variants (putative low risk genotypes) were each associated with an approximately 30% reduction in risk of breast cancer. Risk of breast cancer decreased with increasing number of low risk AGTR1 genotypes after adjustment for potential confounders. Relative to those carrying no low risk genotypes (homozygous for A, C and T alleles for the three polymorphisms, respectively), the odds ratios (95% confidence intervals) were 0.84 (0.51-1.37) for women possessing one low risk genotype and 0.68 (0.46-1.01) for women possessing two or three low risk genotypes (P for trend = 0.05). When both AGTR1 and ACE gene polymorphisms were examined simultaneously, women possessing at least one AGTR1 low risk genotype in combination with the ACE low activity genotype had an odds ratio of 0.35 (95% confidence interval, 0.20-0.62) compared with those possessing the ACE high activity genotype and no AGTR1 low risk genotype. Our findings suggest that pharmacological inhibition of the angiotensin II effect by blockade of ACE and/or AGTR1 could be potential targets for the prevention and treatment of breast cancer.

  11. [Polymorphic markers of GNB3 (C825T), AGTR1 (A1166C) and ACE (A2350G and I/D) genes in patients with arterial hypertension combined with diabetes mellitus type 2].

    PubMed

    Karpov, R S; Puzyrev, K V; Koshel'skaia, O A; Makeeva, O A; Suslova, T E; Efimova, E V; Fal'kovskaia, A Iu; Atroshenkov, A V

    2004-01-01

    To elicit correlations of polymorphic markers of GNB3 (C825T), AGTR1 (A1166C), ACE (A2350G and I/D) genes with arterial pressure, left ventricular hypertrophy (LVH) and blood concentrations of proinflammatory cytokines in hypertensive patients with diabetes mellitus type 2 (DM2). Clinical parameters (24-h arterial pressure profile, echocardiographic findings, immunoenzymes level) were studied in 89 hypertensive patients with DM2. These patients had different genotypes by the studied allele variants of the genes determined by polymerase chain reaction. Polymorphism of A1166C gene of type 1 vascular receptor of angiotensin II (AGTR1) contributes to formation of arterial hypertension (AH) signs diversity in DM2 patients. GNB3, a gene C825T polymorphic marker, showed a correlation with diastolic arterial pressure but this variant of the gene locus is not associated with LVH. However, G-allele of ACE gene contributes much to appearance of this pathological sign. Mean values of IL-1beta and TNF-alpha as well as the presence of LVH depended on genotypes by ACE gene (polymorphism I/D). Polymorphic markers of ACE and GNB3 candidate genes influence clinical diversity of pathological signs in DM2 patients through modification of AH and LVH severity and the level of proinflammatory cytokines.

  12. The Evaluation of Dipeptidyl Peptidase (DPP)-IV, α-Glucosidase and Angiotensin Converting Enzyme (ACE) Inhibitory Activities of Whey Proteins Hydrolyzed with Serine Protease Isolated from Asian Pumpkin (Cucurbita ficifolia).

    PubMed

    Konrad, Babij; Anna, Dąbrowska; Marek, Szołtysik; Marta, Pokora; Aleksandra, Zambrowicz; Józefa, Chrzanowska

    2014-01-01

    In the present study, whey protein concentrate (WPC-80) and β-lactoglobulin were hydrolyzed with a noncommercial serine protease isolated from Asian pumpkin (Cucurbita ficifolia). Hydrolysates were further fractionated by ultrafiltration using membranes with cut-offs equal 3 and 10 kDa. Peptide fractions of molecular weight lower than 3 and 3-10 kDa were further subjected to the RP-HPLC. Separated preparations were investigated for their potential as the natural inhibitors of dipeptidyl peptidase (DPP-IV), α-glucosidase and angiotensin converting enzyme (ACE). WPC-80 hydrolysate showed higher inhibitory activities against the three tested enzymes than β-lactoglobulin hydrolysate. Especially high biological activities were exhibited by peptide fractions of molecular weight lower than 3 kDa, with ACE IC50 <0.64 mg/mL and DPP-IV IC50 <0.55 mg/mL. This study suggests that peptides generated from whey proteins may support postprandial glycemia regulation and blood pressure maintenance, and could be used as functional food ingredients in the diet of patients with type 2 diabetes.

  13. Triple ACE-ECE-NEP inhibition in heart failure: a comparison with ACE and dual ECE-NEP inhibition.

    PubMed

    Mellin, Virginie; Jeng, Arco Y; Monteil, Christelle; Renet, Sylvanie; Henry, Jean Paul; Thuillez, Christian; Mulder, Paul

    2005-09-01

    Mortality remains high in chronic heart failure (CHF) because under ACE inhibitor treatment other neurohumoral systems remain/become (de)activated, such as the endothelin and atrial natriuretic peptide pathways. Dual endothelin-converting enzyme-neutral endopeptidase (ECE-NEP) inhibition exerts beneficial effects in experimental CHF, but whether "triple" ACE-ECE-NEP inhibition is superior to ACE or ECE-NEP inhibition is unknown. We compared, in rats with CHF, ACE-ECE-NEP to ACE or ECE-NEP inhibition in terms of left ventricular (LV) hemodynamics and remodeling. Benazepril (2 mg/kg/d) or the ECE-NEP inhibitor CGS26303 (10 mg/kg/d) were administered alone or in combination (subcutaneously for 28 days starting 7 days after coronary ligation). ACE-ECE-NEP inhibition reduced blood pressure more markedly than ACE or ECE-NEP inhibition. All treatments increased cardiac output to the same extent, but ACE-ECE-NEP inhibition reduced LV diameter and LV end-diastolic pressure more markedly than ACE or ECE-NEP inhibition. The reduction of LV weight and collagen accumulation in the "viable" myocardium was most pronounced after ACE-ECE-NEP inhibition. These results, obtained in experimental CHF, illustrate a further improvement of LV hemodynamics and structure after ACE-ECE-NEP inhibition compared with either ACE or ECE-NEP inhibition, but whether this is associated with a further improvement of exercise tolerance and/or survival remains to be determined.

  14. Enzymes To Die For: Exploiting Nucleotide Metabolizing Enzymes for Cancer Gene Therapy

    PubMed Central

    Ardiani, Andressa; Johnson, Adam J.; Ruan, Hongmei; Sanchez-Bonilla, Marilyn; Serve, Kinta; Black, Margaret E.

    2012-01-01

    Suicide gene therapy is an attractive strategy to selectively destroy cancer cells while minimizing unnecessary toxicity to normal cells. Since this idea was first introduced more than two decades ago, numerous studies have been conducted and significant developments have been made to further its application for mainstream cancer therapy. Major limitations of the suicide gene therapy strategy that have hindered its clinical application include inefficient directed delivery to cancer cells and the poor prodrug activation capacity of suicide enzymes. This review is focused on efforts that have been and are currently being pursued to improve the activity of individual suicide enzymes towards their respective prodrugs with particular attention to the application of nucleotide metabolizing enzymes in suicide cancer gene therapy. A number of protein engineering strategies have been employed and our discussion here will center on the use of mutagenesis approaches to create and evaluate nucleotide metabolizing enzymes with enhanced prodrug activation capacity and increased thermostability. Several of these studies have yielded clinically important enzyme variants that are relevant for cancer gene therapy applications because their utilization can serve to maximize cancer cell killing while minimizing the prodrug dose, thereby limiting undesirable side effects. PMID:22384805

  15. Effect of mitochondrial, APOE, ACE and NOS3 gene polymorphisms on cardiovascular risk factors among the Vaqueiros de Alzada, a Northern Spain human isolate.

    PubMed

    Gómez, Pedro; Gómez, Juan; Corao, Ana I; De Canga, Julio; Coto, Eliecer

    2014-01-01

    The Vaqueiros de Alzada are a human isolate from Asturias, a Northern Spain region. Several hypotheses have been proposed to explain the origin of Vaqueiros. To determine whether the Vaqueiros and non-Vaqueiros from the same region have different genetic backgrounds, this study analysed nine mtDNA polymorphisms that define the common European mitochondrial haplogroups in a cohort of Vaqueiros (n = 60) and non-Vaqueiros (n = 110). Haplogroup H was the most frequent in Vaqueiros (42%) and non-Vaqueiros (46%). A total of 37% Vaqueiros were H1, compared to 31% of the non-Vaqueiros. This study also genotyped the two groups for three polymorphisms at the NOS3. APOE and ACE genes, that have previously been linked to risk of cardiovascular diseases. Allele and genotype frequencies did not differ between Vaqueiros and non-Vaqueiros. In addition, none of these polymorphisms were related to risk of hypertension, diabetes or hypercholesterolaemia in the two groups. The data suggested that Vaqueiros share the main haplogroup distribution as their non-Vaqueiros neighbours and other Cantabrian populations. In addition, no effect of the mitochondrial, NOS3. APOE and ACE polymorphisms on cardiovascular risk factors was observed.

  16. Microdiversity of extracellular enzyme genes among sequenced prokaryotic genomes

    PubMed Central

    Zimmerman, Amy E; Martiny, Adam C; Allison, Steven D

    2013-01-01

    Understanding the relationship between prokaryotic traits and phylogeny is important for predicting and modeling ecological processes. Microbial extracellular enzymes have a pivotal role in nutrient cycling and the decomposition of organic matter, yet little is known about the phylogenetic distribution of genes encoding these enzymes. In this study, we analyzed 3058 annotated prokaryotic genomes to determine which taxa have the genetic potential to produce alkaline phosphatase, chitinase and β-N-acetyl-glucosaminidase enzymes. We then evaluated the relationship between the genetic potential for enzyme production and 16S rRNA phylogeny using the consenTRAIT algorithm, which calculated the phylogenetic depth and corresponding 16S rRNA sequence identity of clades of potential enzyme producers. Nearly half (49.2%) of the genomes analyzed were found to be capable of extracellular enzyme production, and these were non-randomly distributed across most prokaryotic phyla. On average, clades of potential enzyme-producing organisms had a maximum phylogenetic depth of 0.008004–0.009780, though individual clades varied broadly in both size and depth. These values correspond to a minimum 16S rRNA sequence identity of 98.04–98.40%. The distribution pattern we found is an indication of microdiversity, the occurrence of ecologically or physiologically distinct populations within phylogenetically related groups. Additionally, we found positive correlations among the genes encoding different extracellular enzymes. Our results suggest that the capacity to produce extracellular enzymes varies at relatively fine-scale phylogenetic resolution. This variation is consistent with other traits that require a small number of genes and provides insight into the relationship between taxonomy and traits that may be useful for predicting ecological function. PMID:23303371

  17. Quantitative assessment of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism and digestive system cancer risk.

    PubMed

    Wang, J; Yang, S; Guo, F H; Mao, X; Zhou, H; Dong, Y Q; Wang, Z M; Luo, F

    2015-11-13

    The angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been reported to be associated with digestive system cancer; however, the results from previous studies have been conflicting. The present study aimed to investigate the association between the ACE I/D polymorphism and the risk of digestive system cancer using a meta-analysis of previously published studies. Databases were systematically searched to identify relevant studies published prior to December 2014. We estimated the pooled OR with its 95%CI to assess the association. The meta-analysis consisted of thirteen case-control studies that included 2557 patients and 4356 healthy controls. Meta-analysis results based on all the studies showed no significant association between the ACE I/D polymorphism and the risk of digestive system cancer (DD vs II: OR = 0.85, 95%CI = 0.59-1.24; DI vs II: OR = 0.94, 95%CI = 0.78-1.15; dominant model: OR = 0.96, 95%CI = 0.81- 1.15; recessive model: OR = 1.06, 95%CI = 0.76-1.48). Subgroup analyses by race and cancer type did not detect an association between the ACE I/D polymorphism and digestive system cancer risk. However, when the analyses were restricted to smaller studies (N < 500 patients), the summary OR of DI vs II was 0.80 (95%CI = 0.66-0.97). Our analyses detected a possibility of publication bias with a misestimate of the true association by smaller studies. Overall, meta-analysis results suggest the ACE I/D polymorphism might not be associated with susceptibility to digestive system cancer. Further large and well-designed studies are needed to confirm these conclusions.

  18. Distribution of ACE insertion/deletion (I/D) polymorphism in Iranian populations

    PubMed Central

    Saadat, Mostafa

    2015-01-01

    Angiotensin converting enzyme (ACE; OMIM: 106180) has an important role in the conversion of angiotensin I to angiotensin II and degradation of bradykinin. Genetic polymorphism I/D (rs4646994) in the gene encoding ACE has been well defined. To get more insight into the genetic structure of Iranian populations, the distribution of the ACE I/D polymorphism among Iranians was compared with each other and with other populations. Prevalence of the D allele was 0.5886 (95% CI: 0.5725-0.6047) in Iran. There was significant difference between Iranian populations (x2=27.7, df=6, P<0.001). The major part of this difference was due to difference between Zahedan study and the other populations, as by removing this population, the heterogeneity between populations, remarkably decreased (x2=10.15, df=5, P=0.071). The D allele showed high frequency in Iran which is similar to Caucasians. PMID:27843997

  19. Association of ACE gene D polymorphism with left ventricular hypertrophy in patients with diastolic heart failure: a case-control study.

    PubMed

    Bahramali, Ehsan; Rajabi, Mona; Jamshidi, Javad; Mousavi, Seyyed Mohammad; Zarghami, Mehrdad; Manafi, Alireza; Firouzabadi, Negar

    2016-02-09

    To explore the association between ACE gene insertion/deletion (I/D) polymorphism with left ventricular hypertrophy (LVH) in patients with hypertension who have developed heart failure with preserved ejection fraction (HFpEF). Being a major contributor to the development of diastolic heart dysfunction, the renin angiotensin aldosterone system and its genetic variations are thought to induce LVH in hypertensive hearts apart from haemodynamic factors. Case control study. An Iranian referral university hospital. 176 patients with hypertension and a diagnosis of HFpEF on presence of symptoms of heart failure plus Doppler echocardiographic documentation of left ventricular (LV) diastolic dysfunction and/or elevated NT-proBNP levels. Those with significant coronary, valvular, pericardial and structural heart diseases were excluded as well as patients with atrial fibrillation, renal failure and pulmonary causes of dyspnoea. They were divided into two cohorts of 88 cases with and 88 controls without LVH, after determination of LV mass index, using two-dimensional and M-mode echocardiography. The I/D polymorphism of the ACE gene was determined using the PCR method. The D allele was significantly more prevalent among cases with compared with controls without LVH (p=0.0007). Genotype distributions also differed significantly under additive (p=0.005, OR=0.53, 95% CI 0.34 to 0.84) and recessive (p=0.001, OR=0.29, 95% CI 0.13 to 0.66) models. In patients with hypertension who develop HFpEF, the D allele of the ACE gene is probably associated with the development of LVH. With the detrimental effects of LVH on the heart's diastolic properties, this can signify the role of genetic contributors to the development of HFpEF in patients with hypertension and may serve as a future risk predictor for the disease. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  20. Characterization of the mammalian DNA polymerase gene(s) and enzyme(s). Annual progress report

    SciTech Connect

    Mishra, N.C.

    1995-01-01

    Two Genes for DNA polymerase delta were identified from the wild type Chinese hamster ovary cells. These genes were cloned via RT-PCR from mRNA prepared the Chinese hamster ovary cells using primers specific to conserved sequences of the DNA polymerase {delta} gene. The first gene encodes a PCNA dependent DNA polymerase {delta} gene whereas the second gene encodes a PCNA independent DNA polymerase {delta} gene. Methods were developed to clone these genes in expression vector and host systems. The role of the two genes in DNA replication and repair was determined.

  1. Brain-targeted ACE2 overexpression attenuates neurogenic hypertension by inhibiting COX mediated inflammation

    PubMed Central

    Sriramula, Srinivas; Xia, Huijing; Xu, Ping; Lazartigues, Eric

    2014-01-01

    Overactivity of the renin angiotensin system (RAS), oxidative stress, and cyclooxygenases (COX) in the brain are implicated in the pathogenesis of hypertension. We previously reported that Angiotensin-Converting Enzyme 2 (ACE2) overexpression in the brain attenuates the development of DOCA-salt hypertension, a neurogenic hypertension model with enhanced brain RAS and sympathetic activity. To elucidate the mechanisms involved, we investigated whether oxidative stress, mitogen activated protein kinase signaling and cyclooxygenase (COX) activation in the brain are modulated by ACE2 in neurogenic hypertension. DOCA-salt hypertension significantly increased expression of Nox-2 (+61 ±5 %), Nox-4 (+50 ±13 %) and nitrotyrosine (+89 ±32 %) and reduced activity of the antioxidant enzymes, catalase (−29 ±4 %) and SOD (−31 ±7 %), indicating increased oxidative stress in the brain of non-transgenic mice. This increased oxidative stress was attenuated in transgenic mice overexpressing ACE2 in the brain. DOCA-salt-induced reduction of nNOS expression (−26 ±7 %) and phosphorylated eNOS/total eNOS (−30 ±3 %), and enhanced phosphorylation of Akt and ERK1/2 in the paraventricular nucleus (PVN), were reversed by ACE2 overexpression. In addition, ACE2 overexpression blunted the hypertension-mediated increase in gene and protein expression of COX-1 and COX-2 in the PVN. Furthermore, gene silencing of either COX-1 or COX-2 in the brain, reduced microglial activation and accompanied neuro-inflammation, ultimately attenuating DOCA-salt hypertension. Together, these data provide evidence that brain ACE2 overexpression reduces oxidative stress and COX-mediated neuro-inflammation, improves anti-oxidant and nitric oxide signaling, and thereby attenuates the development of neurogenic hypertension. PMID:25489058

  2. Angiotensin converting enzyme gene polymorphism is associated with severity of coronary artery disease in men with high total cholesterol levels.

    PubMed

    Borzyszkowska, Joanna; Stanislawska-Sachadyn, Anna; Wirtwein, Marcin; Sobiczewski, Wojciech; Ciecwierz, Dariusz; Targonski, Radoslaw; Gruchala, Marcin; Rynkiewicz, Andrzej; Limon, Janusz

    2012-05-01

    This study examines whether renin-angiotensin-aldosterone system gene polymorphisms: ACE (encoding for angiotensin converting enzyme) c.2306-117_404 I/D, AGTR1 (encoding for angiotensin II type-1 receptor) c.1080*86A>C and CYP11B2 (encoding for aldosterone synthase) c.-344C>T are associated with the extension of coronary atherosclerosis in a group of 647 patients who underwent elective coronary angiography. The extension of CAD was evaluated using the Gensini score. The polymorphisms were determined by PCR and RFLP assays. The associations between genotypes and the extent of coronary atherosclerosis were tested by the Kruskal-Wallis test, followed by pairwise comparisons using Wilcoxon test. The population has been divided into groups defined by: sex, smoking habit, past myocardial infarction, BMI (>, ≤ 25), age (>, ≤ 55), diabetes mellitus, level of total cholesterol (>, ≤ 200 mg/dl), LDL cholesterol (>, ≤ 130 mg/dl), HDL cholesterol (>, ≤ 40 mg/dl), triglycerides (>, ≤ 150 mg/dl). Significant associations between the ACE c.2306-117_404 I/D polymorphism and the Gensini score in men with high total cholesterol levels (P(Kruskal-Wallis) = 0.008; P(adjusted) = 0.009), high level of LDL cholesterol (P(Kruskal-Wallis) = 0.016; P(adjusted) = 0.028) and low level of HDL cholesterol (P(Kruskal-Wallis) = 0.04; P(adjusted) = 0.055) have been found. No association between the AGTR1 c.1080*86A>C and CYP11B2 c.-344C>T and the Gensini score has been found. These results suggest that men who carry ACE c.2306-117_404 DD genotype and have high total cholesterol, high LDL cholesterol and low HDL cholesterol levels may be predisposed to the development of more severe CAD.

  3. Association of cardiovascular response to an acute resistance training session with the ACE gene polymorphism in sedentary women: a randomized trial

    PubMed Central

    2013-01-01

    Background The aim of the present study was to verify the effects of an acute resistance training (RT) session and insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) on systolic (SBP), diastolic (DBP) and mean blood pressure (MBP), and heart rate (HR). Methods The sample consisted of 27 sedentary women (33.3 ± 8.2 yrs; 69.1 ± 13.8 kg; 1.57 ± 0.05 m; 27.6 ± 5.1 kg/m2) divided into two groups according to their polymorphism I/D (DD = 9; II + ID = 18). Volunteers underwent two experimental sessions: RT – an acute session performed with three sets at 60% of one-repetition maximum (1RM) interspersed with 1 minute rest interval between exercises and sets, and a control session (CON) in which they remained seated for 30 minutes in the laboratory. SBP, DBP, MBP and HR were measured before exercise and during one hour every 10 minutes after sessions, in the seated position. A two-way ANOVA for repeated measures with Tukey’s post hoc test was used for the intra and inter-group comparisons. Results There were no statistically significant differences on SBP, DBP and MBP after the experimental protocols, and no effect of ACE polymorphism (P > 0.05). However, comparing CON versus exercise effect size values (ES), homozygotic carriers of the allele D presented a drop in SBP which was considered moderate, while in allele I carriers it was small, 30 minutes after exercise. In MBP, homozygotic D carriers exhibited a large ES 20 minutes post-exercise. HR was higher at 10, 20 and 30 minutes after exercise as compared to pre-exercise only for carriers of the I allele (P < 0.05). Conclusions Therefore, an acute RT session reduces clinical BP. In addition to this; it seems that ACE polymorphism had some influence on cardiovascular response to exercise. Trial Registration RBR-6GDYVZ PMID:23305118

  4. Undercover: gene control by metabolites and metabolic enzymes

    PubMed Central

    van der Knaap, Jan A.; Verrijzer, C. Peter

    2016-01-01

    To make the appropriate developmental decisions or maintain homeostasis, cells and organisms must coordinate the expression of their genome and metabolic state. However, the molecular mechanisms that relay environmental cues such as nutrient availability to the appropriate gene expression response remain poorly understood. There is a growing awareness that central components of intermediary metabolism are cofactors or cosubstrates of chromatin-modifying enzymes. As such, their concentrations constitute a potential regulatory interface between the metabolic and chromatin states. In addition, there is increasing evidence for a direct involvement of classic metabolic enzymes in gene expression control. These dual-function proteins may provide a direct link between metabolic programing and the control of gene expression. Here, we discuss our current understanding of the molecular mechanisms connecting metabolism to gene expression and their implications for development and disease. PMID:27881599

  5. Segregation and linkage analysis of serum angiotensin I-converting enzyme levels: Evidence for two quantitative-trait loci

    SciTech Connect

    McKenzie, C.A.; Keavney, B.; Farrall, M.

    1995-12-01

    Human serum angiotensin I-converting enzyme (ACE) levels vary substantially between individuals and are highly heritable. Segregation analysis in European families has shown that more than half of the total variability in ACE levels is influenced by quantitative-trait loci (QTL). One of these QTLs is located within or close to the ACE locus itself. Combined segregation/linkage analysis in a series of African Caribbean families from Jamaica shows that the ACE insertion-deletion polymorphism is in moderate linkage disequilibrium with an ACE-linked QTL. Linkage analysis with a highly informative polymorphism at the neighboring growth hormone gene (GH) shows surprisingly little support for linkage (LOD score [Z] = 0.12). An extended analysis with a two-QTL model, where an ACE-linked QTL interacts additively with an unlinked QTL, significantly improves both the fit of the model (P = .002) and the support for linkage between the ACE-linked QTL and GH polymorphism (Z = 5.0). We conclude that two QTLs jointly influence serum ACE levels in this population. One QTL is located within or close to the ACE locus and explains 27% of the total variability; the second QTL is unlinked to the ACE locus and explains 52% of the variability. The identification of the molecular mechanisms underlying both QTLs is necessary in order to interpret the role of ACE in cardiovascular disease. 44 refs., 7 tabs.

  6. Angiotensin-converting enzyme 2/angiotensin-(1–7)/Mas axis activates Akt signaling to ameliorate hepatic steatosis

    PubMed Central

    Cao, Xi; Yang, Fangyuan; Shi, Tingting; Yuan, Mingxia; Xin, Zhong; Xie, Rongrong; Li, Sen; Li, Hongbing; Yang, Jin-Kui

    2016-01-01

    The classical axis of renin-angiotensin system (RAS), angiotensin (Ang)-converting enzyme (ACE)/Ang II/AT1, contributes to the development of non-alcoholic fatty liver disease (NAFLD). However, the role of bypass axis of RAS (Angiotensin-converting enzyme 2 (ACE2)/Ang-(1–7)/Mas) in hepatic steatosis is still unclear. Here we showed that deletion of ACE2 aggravates liver steatosis, which is correlated with the increased expression of hepatic lipogenic genes and the decreased expression of fatty acid oxidation-related genes in the liver of ACE2 knockout (ACE2−/y) mice. Meanwhile, oxidative stress and inflammation were also aggravated in ACE2−/y mice. On the contrary, overexpression of ACE2 improved fatty liver in db/db mice, and the mRNA levels of fatty acid oxidation-related genes were up-regulated. In vitro, Ang-(1–7)/ACE2 ameliorated hepatic steatosis, oxidative stress and inflammation in free fatty acid (FFA)-induced HepG2 cells, and what’s more, Akt inhibitors reduced ACE2-mediated lipid metabolism. Furthermore, ACE2-mediated Akt activation could be attenuated by blockade of ATP/P2 receptor/Calmodulin (CaM) pathway. These results indicated that Ang-(1–7)/ACE2/Mas axis may reduce liver lipid accumulation partly by regulating lipid-metabolizing genes through ATP/P2 receptor/CaM signaling pathway. Our findings support the potential role of ACE2/Ang-(1–7)/Mas axis in prevention and treatment of hepatic lipid metabolism. PMID:26883384

  7. Marketing ACE in Victoria.

    ERIC Educational Resources Information Center

    2001

    This publication presents options raised through various forums for marketing adult and community education (ACE) in Victoria, Australia, and suggested strategies. After an introduction (chapter 1), chapters 2 and 3 provide a broad view of the current situation for marketing ACE. Chapter 2 discusses general issues in the current position--ACE…

  8. Resveratrol Inhibits Growth of Experimental Abdominal Aortic Aneurysm Associated With Upregulation of Angiotensin-Converting Enzyme 2.

    PubMed

    Moran, Corey S; Biros, Erik; Krishna, Smriti M; Wang, Yutang; Tikellis, Chris; Moxon, Joseph V; Cooper, Mark E; Norman, Paul E; Burrell, Louise M; Thomas, Merlin C; Golledge, Jonathan

    2017-09-21

    Recent evidence suggests an important role for angiotensin-converting enzyme 2 (ACE2) in limiting abdominal aortic aneurysm (AAA). This study examined the effect of ACE2 deficiency on AAA development and the efficacy of resveratrol to upregulate ACE2 in experimental AAA. APPROACH AND RESULTS: Ace2 deletion in apolipoprotein-deficient mice (ApoE(-/)(-)Ace2(-/y) ) resulted in increased aortic diameter and spontaneous aneurysm of the suprarenal aorta associated with increased expression of inflammation and proteolytic enzyme markers. In humans, serum ACE2 activity was negatively associated with AAA diagnosis. ACE2 expression was lower in infrarenal biopsies of patients with AAA than organ donors. AAA was more severe in ApoE(-/-)Ace2(-/y) mice compared with controls in 2 experimental models. Resveratrol (0.05/100-g chow) inhibited growth of pre-established AAAs in ApoE(-/-) mice fed high-fat chow and infused with angiotensin II continuously for 56 days. Reduced suprarenal aorta dilatation in mice receiving resveratrol was associated with elevated serum ACE2 and increased suprarenal aorta tissue levels of ACE2 and sirtuin 1 activity. In addition, the relative phosphorylation of Akt and ERK (extracellular signal-regulated kinase) 1/2 within suprarenal aorta tissue and gene expression for nuclear factor of kappa light polypeptide gene enhancer in B cells 1, angiotensin type-1 receptor, and metallopeptidase 2 and 9 were significantly reduced. Upregulation of ACE2 in human aortic smooth muscle cells by resveratrol in vitro was sirtuin 1-dependent. This study provides experimental evidence of an important role for ACE2 in limiting AAA development and growth. Resveratrol upregulated ACE2 and inhibited AAA growth in a mouse model. © 2017 American Heart Association, Inc.

  9. Angiotensin I-converting enzyme gene polymorphism in two ethnic groups living in Brazil's southern region: association with age.

    PubMed

    Da Cruz, Ivana Beatrice Mânica; Oliveira, Graziela; Taufer, Maristela; Leal, Ney Furhmann; Schwanke, Carla Helena; Glock, Luiz; Moriguchi, Yukio; Moriguchi, Emilio Hideyuki

    2003-09-01

    Several studies have been published on the association between ACE (angiotensin I-converting enzyme) polymorphism and longevity. However, the results are controversial. We analyzed the association between ACE polymorphism and age in two different ethnic populations: a population originating from different European countries (Gaucha Population, GP) and a population originating from Japan (JP). Both populations live in Brazil's southern region. We determined the ACE genotype in 834 persons aged 10-104 years. The ACE genotype and allele frequencies differed between the two populations, with the D allele being more frequent in GP than JP. We found an association between the DD genotype and D allele and age in the GP group only. The ACE polymorphism-age association occurred at age >60 years in the GP population with decreasing II frequency. We cannot dismiss the possibility of the association between ACE polymorphism and age involving linkage disequilibrium, since the nature of this phenomenon is still controversial. From our studies, it appears that there is a correlation between age, ethnicity, and ACE polymorphism. More of such studies are warranted, as further investigation in this area will have a high clinical relevance to cardiovascular disease and aging research.

  10. Isolated gene encoding an enzyme with UDP-glucose pyrophosphorylase and phosphoglucomutase activities from Cyclotella cryptica

    DOEpatents

    Jarvis, E.E.; Roessler, P.G.

    1999-07-27

    The present invention relates to a cloned gene which encodes an enzyme, the purified enzyme, and the applications and products resulting from the use of the gene and enzyme. The gene, isolated from Cyclotella cryptica, encodes a multifunctional enzyme that has both UDP-glucose pyrophosphorylase and phosphoglucomutase activities. 8 figs.

  11. Isolated gene encoding an enzyme with UDP-glucose pyrophosphorylase and phosphoglucomutase activities from Cyclotella cryptica

    DOEpatents

    Jarvis, Eric E.; Roessler, Paul G.

    1999-01-01

    The present invention relates to a cloned gene which encodes an enzyme, the purified enzyme, and the applications and products resulting from the use of the gene and enzyme. The gene, isolated from Cyclotella cryptica, encodes a multifunctional enzyme that has both UDP-glucose pyrophosphorylase and phosphoglucomutase activities.

  12. ACE and AGTR1 polymorphisms and left ventricular hypertrophy in endurance athletes.

    PubMed

    Di Mauro, Michele; Izzicupo, Pascal; Santarelli, Francesco; Falone, Stefano; Pennelli, Alfonso; Amicarelli, Fernanda; Calafiore, Antonio M; Di Baldassarre, Angela; Gallina, Sabina

    2010-05-01

    This study aimed to evaluate the role of angiotensin type 1 receptor gene (AGTR1) polymorphism (A1166C) in left ventricular hypertrophy (LVH) mediated by the angiotensin-converting enzyme (ACE) in endurance athletes. A group of 74 white, healthy male endurance athletes, aged between 25 and 40 yr, were enrolled in this study. All of them participated primarily in isotonic sports, training for at least >10 h x wk(-1), for at least 5 yr. The ACE genotype (insertion [I] or deletion [D] alleles) was ascertained by polymerase chain reaction (DD in 35, ID in 36, and II in 3). Group II was excluded from the analysis because of its small size. No difference was found between the two groups as regards age, blood pressure, HR, and echocardiographic data. The left ventricular mass index (LVMI) was significantly higher in group DD rather than in group ID (P = 0.029). The group DD showed a slightly higher prevalence of subjects with LVH (LVMI > 131 g x m(-2); 62.9%) than group ID (44.4%, P = 0.120). No association was found between ACE-DD and LVH (odds ratio (OR) = 2.12, 95% confidence interval = 0.82-5.46). Concerning the role of AGTR1 polymorphism, the highest LVMI was found in 15 athletes with ACE-DD and AGTR1-AC/CC genotypes (150 +/- 23 g x m(-2)); the lowest value of LVMI was found in the case of ACE-ID and AGTR1-AA (127 g x m(-2) +/- 18 g x m(-2)), whereas LVMI in subjects with ACE-DD + AGTR1-AA was similar to that in the ACE-ID + AGTR1-AC/CC group (134 +/- 18 g x m(-2) vs 133 +/- 20 g x m(-2), P = 0.880). The presence of ACE-DD + AGTR1 + AC/CC was strongly associated with LVH (OR = 4.6, P = 0.029). Moreover, subjects with LVH showed longer left ventricular isovolumetric relaxation time and higher end-systolic wall stress. The latter was strongly correlated to LVMI (r = 0.588), especially in the presence of ACE-DD + AGTR1 + AC/CC (r = 0.728). LVMI may be greater in the presence of ACE- DD and AGTR1-AC/CC polymorphisms.

  13. Gene polymorphisms of angiotensin-converting enzyme and angiotensin II type 1 receptor among chronic kidney disease patients in a Chinese population.

    PubMed

    Su, Sui-Lung; Lu, Kuo-Cheng; Lin, Yuh-Feng; Hsu, Yu-Juei; Lee, Pong-Ying; Yang, Hsin-Yi; Kao, Sen-Yeong

    2012-03-01

    Chronic kidney disease (CKD) is highly prevalent in Taiwan and an increasing number of patients are affected, with a high risk of progression to end-stage renal disease and huge medical expenses. It has been predicted that the presence of hypertension increases with decreasing renal function due to a decrease in sodium excretion and activation of the renin-angiotensin system (RAS). The aim of this study was to investigate the influence of genetic variants of the RAS gene on CKD. We performed a case control association study and genotyped 135 CKD patients and 270 healthy controls among Han Chinese in Taiwan. All subjects were genotyped for angiotensinogen (AGT-M235T, T174M, A-20C), angiotensin-I converting enzyme (ACE-A2350G) and angiotensin II type 1 receptor (AGTR1-A1166C, C573T, C-521T) polymorphisms of RAS genes by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Significant associations were observed in ACE-A2350G and AGTR1-C573T polymorphism between CKD patients and controls. In regard to ACE-A2350G, compared with the AA genotype the GG genotype protected against CKD (adjusted odds ratio [OR] = 0.34; p = 0.01). In regard to AGTR1-C573T, the CT genotype was a risk for CKD compared with the CC genotype (adjusted OR = 1.82; p = 0.03). We conclude that ACE-A2350G and AGTR1-C573T polymorphisms are likely candidate determinants of CKD.

  14. ACE insertion/deletion polymorphism is associated with periodontal disease in Korean population.

    PubMed

    Kang, Sang Wook; Han, Seung Yeop; Lim, Sung Bin; Cho, Kyu Bong; Ban, Ju Yeon

    2015-03-01

    Angiotensin-converting enzyme (ACE) is the core enzyme in the renin-angiotensin system (RAS), which catalyzes the production of angiotensin II (Ang II). The aim of this study was to determine whether ACE gene is associated with the development of the periodontal disease. To investigate whether ACE is involved in the development of the periodontal disease, 199 periodontal disease patients and 165 control subjects were studied. The ACE insertion/deletion polymorphism was analyzed using polymerase chain reaction (PCR). SNPStats and SPSS 18.0 were used for the analysis of genetic data. Logistic regression models were performed to determine odds ratio (OR), 95% confidence interval (CI), and P value. Genotypic frequencies of I/I, I/D, and D/D were 25.4%, 42.3%, and 32.3% vs. 35.3%, 41.7%, and 23.1% (periodontal disease group vs. control group), respectively. In the genotype analysis of the ACE insertion/deletion polymorphism, codominant and log-additive models both showed significant association with periodontal disease [OR = 1.94, 95% CI = 1.05-3.61, P=0.036 in the codominant model (I/I vs. D/D); OR = 1.39, 95% CI = 1.02-1.90, P = 0.034 in the log-additive model (I/I vs. I/D vs. D/D)]. These results suggest that the ACE insertion/deletion polymorphism may be associated with the susceptibility to the periodontal disease in the Korean population. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Angiotensin-converting enzyme gene insertion/deletion polymorphism in Saudi patients with rheumatic heart disease

    PubMed Central

    Al-Harbi, Khalid M.; Almuzaini, Ibrahim S.; Morsy, Mohamed M.; Abdelaziz, Nada A.; Al-Balawi, Alia M.; Abdallah, Atiyeh M.

    2015-01-01

    Objectives: To investigate the association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and rheumatic heart disease (RHD) in Saudi patients. Methods: A case-control study was conducted in Saudi RHD patients. Genomic DNA was isolated from 99 RHD patients attending the Pediatric Cardiology Clinic at the Maternity and Children Hospital, Al-Madinah, Saudi Arabia from March 2013 to June 2014, and from 145 age- and gender-matched controls. Patient clinical records were reviewed to report major and minor modified Jones’ criteria for diagnosis. The diagnosis was confirmed by echocardiography. The ACE I/D polymorphism was identified by polymerase chain reaction. Results: A significant difference in ACE D allele carriage (DD+ID) distribution between RHD cases and controls was identified (p=0.02, odds ratio = 3.6, 95% confidence interval: 1.2-10.8). The D allele carriage was significantly associated with development of mitral valve lesions alone (p=0.03). Conclusion: The ACE I/D polymorphism is associated with an increased risk of RHD in the Saudi population. Further studies are needed to confirm our findings and to understand the molecular mechanisms underlying this association. PMID:25719581

  16. A Single Nucleotide Polymorphism Uncovers a Novel Function for the Transcription Factor Ace2 during Candida albicans Hyphal Development

    PubMed Central

    Orellana-Muñoz, Sara; Gutiérrez-Escribano, Pilar; Arnáiz-Pita, Yolanda; Dueñas-Santero, Encarnación; Suárez, M. Belén; Bougnoux, Marie-Elisabeth; del Rey, Francisco; Sherlock, Gavin; d’Enfert, Christophe; Correa-Bordes, Jaime; de Aldana, Carlos R. Vázquez

    2015-01-01

    Candida albicans is a major invasive fungal pathogen in humans. An important virulence factor is its ability to switch between the yeast and hyphal forms, and these filamentous forms are important in tissue penetration and invasion. A common feature for filamentous growth is the ability to inhibit cell separation after cytokinesis, although it is poorly understood how this process is regulated developmentally. In C. albicans, the formation of filaments during hyphal growth requires changes in septin ring dynamics. In this work, we studied the functional relationship between septins and the transcription factor Ace2, which controls the expression of enzymes that catalyze septum degradation. We found that alternative translation initiation produces two Ace2 isoforms. While full-length Ace2, Ace2L, influences septin dynamics in a transcription-independent manner in hyphal cells but not in yeast cells, the use of methionine-55 as the initiation codon gives rise to Ace2S, which functions as the nuclear transcription factor required for the expression of cell separation genes. Genetic evidence indicates that Ace2L influences the incorporation of the Sep7 septin to hyphal septin rings in order to avoid inappropriate activation of cell separation during filamentous growth. Interestingly, a natural single nucleotide polymorphism (SNP) present in the C. albicans WO-1 background and other C. albicans commensal and clinical isolates generates a stop codon in the ninth codon of Ace2L that mimics the phenotype of cells lacking Ace2L. Finally, we report that Ace2L and Ace2S interact with the NDR kinase Cbk1 and that impairing activity of this kinase results in a defect in septin dynamics similar to that of hyphal cells lacking Ace2L. Together, our findings identify Ace2L and the NDR kinase Cbk1 as new elements of the signaling system that modify septin ring dynamics in hyphae to allow cell-chain formation, a feature that appears to have evolved in specific C. albicans lineages

  17. Understanding Antegrade Colonic Enema (ACE) Surgery

    MedlinePlus

    ... Enema (ACE) Surgery Understanding Antegrade Colonic Enema (ACE) Surgery Antegrade colonic enema surgery (ACE) or Malone antegrade ... Email Print What is antegrade colonic enema (ACE) surgery? Antegrade colonic enema surgery (ACE) or Malone antegrade ...

  18. Polymorphisms of three genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system are not associated with blood pressure salt sensitivity: A systematic meta-analysis.

    PubMed

    Sun, Jiahong; Zhao, Min; Miao, Song; Xi, Bo

    2016-01-01

    Many studies have suggested that polymorphisms of three key genes (ACE, AGT and CYP11B2) in the renin-angiotensin-aldosterone system (RAAS) play important roles in the development of blood pressure (BP) salt sensitivity, but they have revealed inconsistent results. Thus, we performed a meta-analysis to clarify the association. PubMed and Embase databases were searched for eligible published articles. Fixed- or random-effect models were used to pool odds ratios and 95% confidence intervals based on whether there was significant heterogeneity between studies. In total, seven studies [237 salt-sensitive (SS) cases and 251 salt-resistant (SR) controls] for ACE gene I/D polymorphism, three studies (130 SS cases and 221 SR controls) for AGT gene M235T polymorphism and three studies (113 SS cases and 218 SR controls) for CYP11B2 gene C344T polymorphism were included in this meta-analysis. The results showed that there was no significant association between polymorphisms of these three polymorphisms in the RAAS and BP salt sensitivity under three genetic models (all p > 0.05). The meta-analysis suggested that three polymorphisms (ACE gene I/D, AGT gene M235T, CYP11B2 gene C344T) in the RAAS have no significant effect on BP salt sensitivity.

  19. Human monoamine oxidase A gene determines levels of enzyme activity.

    PubMed Central

    Hotamisligil, G S; Breakefield, X O

    1991-01-01

    Monoamine oxidase (MAO) is a critical enzyme in the degradative deamination of biogenic amines throughout the body. Two biochemically distinct forms of the enzyme, A and B, are encoded in separate genes on the human X chromosome. In these studies we investigated the role of the structural gene for MAO-A in determining levels of activity in humans, as measured in cultured skin fibroblasts. The coding sequence of the mRNA for MAO-A was determined by first-strand cDNA synthesis, PCR amplification, and direct dideoxy sequencing. Two single-basepair substitutions were observed in cDNAs from cells with a 30-fold difference in activity levels. These two substitutions were in the third base of a triplet codon and hence did not affect the deduced amino acid sequence but did affect the presence or absence of restriction-enzyme sites for EcoRV and Fnu4HI, which could be elucidated on PCR fragments derived from genomic DNA or cDNAs. A third polymorphism for MspI in the noncoding region of the MAOA gene was also evaluated by Southern blot analysis using genomic DNA. Statistically significant associations were observed between the alleles for MAOA and levels of MAO activity in human male fibroblast lines. This association indicates that the MAOA gene itself is a major determinant of activity levels, apparently, in part, through noncoding, regulatory elements. Images Figure 3 Figure 4 Figure 5 PMID:1678250

  20. Validated ligand mapping of ACE active site

    NASA Astrophysics Data System (ADS)

    Kuster, Daniel J.; Marshall, Garland R.

    2005-08-01

    Crystal structures of angiotensin-converting enzyme (ACE) complexed with three inhibitors (lisinopril, captopril, enalapril) provided experimental data for testing the validity of a prior active site model predicting the bound conformation of the inhibitors. The ACE active site model - predicted over 18 years ago using a series of potent ACE inhibitors of diverse chemical structure - was recreated using published data and commercial software. Comparison between the predicted structures of the three inhibitors bound to the active site of ACE and those determined experimentally yielded root mean square deviation (RMSD) values of 0.43-0.81 Å, among the distances defining the active site map. The bound conformations of the chemically relevant atoms were accurately deduced from the geometry of ligands, applying the assumption that the geometry of the active site groups responsible for binding and catalysis of amide hydrolysis was constrained. The mapping of bound inhibitors at the ACE active site was validated for known experimental compounds, so that the constrained conformational search methodology may be applied with confidence when no experimentally determined structure of the enzyme yet exists, but potent, diverse inhibitors are available.

  1. Molecular and Recombinational Mapping of Mutations in the Ace Locus of Drosophila melanogaster

    PubMed Central

    Nagoshi, Rodney N.; Gelbart, William M.

    1987-01-01

    The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region within which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize three recessive Ace lethals relative to unselected restriction site variations. These three mutations fall into a segment of 7 kb within the Ace interval. Fine structure recombinational analysis was also used to confirm that the Ace- phenotype of one deletion, Df(3R)AceHD1, co-segregated with the molecular deletion. This deletion does not fully remove Ace activity, but it behaves as a recessive Ace lethal. Df(3R)AceHD1 is the most distal Ace lesion identified and indicates that the Ace locus must extend at least 16 kb. Several poly(A)transcripts are detectable in the region defined by the Ace lesions. The position and extent of the Ace locus, as well as the types of transcripts found, is consistent with the recent findings which identified Torpedo-AChE homologous cDNA sequences in this region. PMID:2826288

  2. Molecular and recombinational mapping of mutations in the Ace locus of Drosophila melanogaster

    SciTech Connect

    Nagoshi, R.N.; Gelbart, W.M.

    1987-11-01

    The Ace locus in Drosophila melanogaster is known to be the structural gene for acetylcholinesterase. Ace is located in a region of chromosome arm 3R which has been subjected to intensive genetic and molecular analysis. Previous deletion mapping studies have identified a 40-kb region with which the Ace gene resides. This report focuses on the further localization of Ace within this 40-kb interval. Within this region, selective fine structure recombinational analysis was employed to localize three recessive Ace lethals relative to unselected restriction site variations. These three mutations fall into a segment of 7 kb within the Ace interval. Fine structure recombinational analysis was also used to confirm that the Ace/sup -/ phenotype of one deletion, Df(3R)Ace/sup HD1/, co-segregated with the molecular deletion. This deletion does not fully remove Ace activity, but it behaves as a recessive Ace lethal. Df(3R)Ace/sup HD1/ is the most distal Ace lesion identified and indicates that the Ace locus must extend at least 16 kb. Several poly(A)transcripts are detectable in the region defined by the Ace lesions. The position and extent of the Ace locus, as well as the types of transcripts found, is consistent with the recent findings which identified Torpedo-AChE homologous cDNA sequences in this region.

  3. Not just angiotensinases: new roles for the angiotensin-converting enzymes.

    PubMed

    Lambert, Daniel W; Clarke, Nicola E; Turner, Anthony J

    2010-01-01

    The renin-angiotensin system (RAS) is a critical regulator of blood pressure and fluid homeostasis. Angiotensin II, the primary bioactive peptide of the RAS, is generated from angiotensin I by angiotensin-converting enzyme (ACE). A homologue of ACE, ACE2, is able to convert angiotensin II to a peptide with opposing effects, angiotensin-(1-7). It is proposed that disturbance of the balance of ACE and ACE2 expression and/or function is important in pathologies in which angiotensin II plays a role. These include cardiovascular and renal disease, lung injury and liver fibrosis. The critical roles of ACE and ACE2 in regulating angiotensin II levels have traditionally focussed attention on their activities as angiotensinases. Recent discoveries, however, have illuminated the roles of these enzymes and of the ACE2 homologue, collectrin, in intracellular trafficking and signalling. This paper reviews the key literature regarding both the catalytic and non-catalytic roles of the angiotensin-converting enzyme gene family.

  4. Association of GSTM1, GSTT1, GSTP1-ILE105VAL and ACE I/D polymorphisms with ankylosing spondylitis.

    PubMed

    İnal, Esra Erkol; Görükmez, Orhan; Eroğlu, Selma; Görükmez, Özlem; Solak, Özlem; Topak, Ali; Yakut, Tahsin

    2016-01-01

    Ankylosing spondylitis (AS) is a chronic inflammatory disease of unknown origin. The aim of this study is to clarify the relationships between susceptibility and severity of AS and GST-mu1 (GSTM1), GST-theta1 (GSTT1), GST-pi1 (GSTP1)-Ile105Val and angiotensin-converting enzyme (ACE) I/D polymorphisms in AS patients. One hundred thirty-eight AS patients and seventy-one healthy controls were enrolled in this study. Erythrocyte sedimentation rate and C-reactive protein (CRP) levels of the AS patients were recorded. The scores of the numeric rating scale (NRS) pain, the Bath Ankylosing Spondylitis Activity Index, the Bath Ankylosing Spondylitis Metrology Index and the Bath Ankylosing Spondylitis Functional Index were calculated. The genotypes distributions and allele frequencies of GSTM1, GSTT1, GSTP1-Ile105Val and ACE I/D polymorphisms were compared between patients and healthy controls. The Multiplex polymerase chain reaction (PCR) and the PCR-restriction fragment length polymorphism methods were used to detect the polymorphisms of ACE I/D, the GSTT1 and GSTM1 genes and the GSTP1-Ile105Val polymorphism, respectively. There were significantly higher levels of the GSTT1 null and the ACE II genotypes in AS patients compared to those in healthy controls (p = 0.002 and 0.005, respectively). We found significantly higher levels of CRP and the NRS pain scores in the patients with ACE ID or DD genotypes compared to those in the patients with ACE II genotypes (p = 0.005 and 0.035, respectively). The present results showed that genes involved in protection from oxidative stress and ACE gene may influence disease development and course in AS.

  5. Regulation of prokaryotic gene expression by eukaryotic-like enzymes

    PubMed Central

    Burnside, Kellie; Rajagopal, Lakshmi

    2011-01-01

    Summary A growing body of evidence indicates that serine/threonine kinases (STK) and phosphatases (STP) regulate gene expression in prokaryotic organisms. As prokaryotic STKs and STPs are not DNA binding proteins, regulation of gene expression is accomplished through post-translational modification of their targets. These include two-component response regulators, DNA binding proteins and proteins that mediate transcription and translation. This review summarizes our current understanding of how STKs and STPs mediate gene expression in prokaryotes. Further studies to identify environmental signals that trigger the signaling cascade and elucidation of mechanisms that regulate cross-talk between eukaryotic-like signaling enzymes, two-component systems, and components of the transcriptional and translational machinery will facilitate a greater understanding of prokaryotic gene regulation. PMID:22221896

  6. Lipid deacylating enzymes in plants: old activities, new genes.

    PubMed

    Matos, Ana Rita; Pham-Thi, Anh-Thu

    2009-06-01

    Because lipids are major components of cellular membranes, their degradation under stress conditions compromises compartmentalization. However, in addition to having structural roles, membrane lipids are also implicated in signalling processes involving the activity of lipolytic enzymes. Phospholipases D and C, acting on the polar heads of phospholipids, have been relatively well characterized in plants. In contrast, knowledge of lipid deacylating enzymes remains limited. Lipid acyl hydrolases (LAH) are able to hydrolyse both fatty acid moieties of polar lipids. They differ from phospholipases A(1) or A(2) (PLA) acting on sn-1 or sn-2 positions of phospholipids, respectively, as well as from lipases which de-esterify triacylglycerols. The free polyunsaturated fatty acids generated by deacylating enzymes can be used in the biosynthesis of oxylipins and the lysophospholipids, provided by PLAs, are also bioactive molecules. In the four decades that have passed since the first description of LAH activities in plants some enzymes have been purified. In recent years, the widespread use of molecular approaches together with the attention paid to lipid signalling has contributed to a renewed interest in LAH and has led to the identification of different gene families and the characterization of new enzymes. Additionally, several proteins with putative lipase/esterase signatures have been identified. In the present paper we review currently available data on LAHs, PLAs, triacylglycerol lipases and other putative deacylating enzymes. The roles of lipid deacylating enzymes in plant growth, development and stress responses are discussed in the context of their involvement in membrane deterioration, lipid turnover and cellular signalling.

  7. FIR ACE samples

    NASA Image and Video Library

    2014-06-04

    ISS040-E-007368 (5 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, works with Advanced Colloids Experiment (ACE) samples in the Destiny laboratory of the International Space Station.

  8. Angiotensin-converting Enzyme Overexpression in Mouse Myelomonocytic Cells Augments Resistance to Listeria and Methicillin-resistant Staphylococcus aureus*

    PubMed Central

    Okwan-Duodu, Derick; Datta, Vivekanand; Shen, Xiao Z.; Goodridge, Helen S.; Bernstein, Ellen A.; Fuchs, Sebastien; Liu, George Y.; Bernstein, Kenneth E.

    2010-01-01

    Gene targeting in ES cells was used to substitute control of angiotensin converting enzyme (ACE) expression from the endogenous promoter to the mouse c-fms promoter. The result is an animal model called ACE 10/10 in which ACE is overexpressed by monocytes, macrophages, and other myelomonocytic lineage cells. To study the immune response of these mice to bacterial infection, we challenged them with Listeria monocytogenes or methicillin-resistant Staphylococcus aureus (MRSA). ACE 10/10 mice have a significantly enhanced immune response to both bacteria in vivo and in vitro. For example, 5 days after Listeria infection, the spleen and liver of ACE 10/10 mice had 8.0- and 5.2-fold less bacteria than wild type mice (WT). In a model of MRSA skin infection, ACE 10/10 mice had 50-fold less bacteria than WT mice. Histologic examination showed a prominent infiltrate of ACE-positive mononuclear cells in the skin lesions from ACE 10/10. Increased bacterial resistance in ACE 10/10 is directly due to overexpression of ACE, as it is eliminated by an ACE inhibitor. Critical to increased immunity in ACE 10/10 is the overexpression of iNOS and reactive nitrogen intermediates, as inhibition of iNOS by the inhibitor 1400W eliminated all in vitro and in vivo differences in innate bacterial resistance between ACE 10/10 and WT mice. Increased resistance to MRSA was transferable by bone marrow transplantation. The overexpression of ACE and iNOS by myelomonocytic cells substantially boosts innate immunity and may represent a new means to address serious bacterial infections. PMID:20937811

  9. Arctic Collaborative Environment (ACE)

    DTIC Science & Technology

    2012-08-01

    distribution is unlimited. Key Data Requirements • Sea Ice – Location: Area, Onset, Growth, Drift, and Decay – Characterization: % Coverage, Thickness...Cloud ACE Developmental Server hosted at UAHuntsville ACE User Community Public Internet Tailored Ice Product Generation (NIC) Arctic Research...distribution is unlimited. Arctic Map 26 July 2012 13 Multi-sensor Analyzed Sea Ice Extent; National Data Buoy Center DISTRIBUTION STATEMENT A

  10. ACE-1 experiment

    NASA Image and Video Library

    2013-06-24

    ISS036-E-019760 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

  11. ACE-1 experiment

    NASA Image and Video Library

    2013-06-24

    In the International Space Stations Destiny laboratory,NASA astronaut Karen Nyberg,Expedition 36 flight engineer,speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

  12. A study of gene–environment interaction on the gene for angiotensin converting enzyme: a combined functional and population based approach

    PubMed Central

    Sayed-Tabatabaei, F; Schut, A; Hofman, A; Bertoli-Avella, A; Vergeer, J; Witteman, J; van Duijn, C M

    2004-01-01

    Introduction: Studies on the role of the insertion/deletion (I/D) polymorphism of the gene coding for angiotensin converting enzyme (ACE) in atherosclerosis have been inconsistent. In a meta-analysis, we recently showed that this relationship is stronger in high risk populations. In this paper, we used a combined functional and population based approach to investigate the gene–environment interaction of the ACE I/D polymorphism in relation to carotid artery wall thickness. Methods: The study was part of the Rotterdam Study, a prospective population based cohort study. In 5321 subjects, IMT was measured in the carotid arteries by ultrasonography and ACE genotype was determined by size analysis of polymerase chain reaction products. Results: In multiple regression analysis, I/D polymorphism and smoking were the main determinants for plasma ACE activity (r2 = 0.28). There was a positive association between the D allele of the I/D polymorphism and carotid artery thickness among current smokers (p = 0.03). Subjects carrying only one of the risk factors (smoking or the D allele) did not show significant differences in IMT compared with the non-/former smokers group carrying two II alleles, while carriers of both risk factors had significant higher IMT. The association was not present in non-/former smokers. Discussion: The results provide further evidence that genetic and environmental factors interact in the formation of the arterial lesions. This study shows that large population based studies can be extremely helpful in unravelling the genetic origin of complex diseases such as atherosclerosis. PMID:14757856

  13. Regulation of urinary ACE2 in diabetic mice.

    PubMed

    Wysocki, Jan; Garcia-Halpin, Laura; Ye, Minghao; Maier, Christoph; Sowers, Kurt; Burns, Kevin D; Batlle, Daniel

    2013-08-15

    Angiotensin-converting enzyme-2 (ACE2) enhances the degradation of ANG II and its expression is altered in diabetic kidneys, but the regulation of this enzyme in the urine is unknown. Urinary ACE2 was studied in the db/db model of type 2 diabetes and stretozotocin (STZ)-induced type 1 diabetes during several physiological and pharmacological interventions. ACE2 activity in db/db mice was increased in the serum and to a much greater extent in the urine compared with db/m controls. Neither a specific ANG II blocker, telmisartan, nor an ACE inhibitor, captopril, altered the levels of urinary ACE2 in db/db or db/m control mice. High-salt diet (8%) increased whereas low-salt diet (0.1%) decreased urinary ACE2 activity in the urine of db/db mice. In STZ mice, urinary ACE2 was also increased, and insulin decreased it partly but significantly after several weeks of administration. The increase in urinary ACE2 activity in db/db mice reflected an increase in enzymatically active protein with two bands identified of molecular size at 110 and 75 kDa and was associated with an increase in kidney cortex ACE2 protein at 110 kDa but not at 75 kDa. ACE2 activity was increased in isolated tubular preparations but not in glomeruli from db/db mice. Administration of soluble recombinant ACE2 to db/m and db/db mice resulted in a marked increase in serum ACE2 activity, but no gain in ACE2 activity was detectable in the urine, further demonstrating that urinary ACE2 is of kidney origin. Increased urinary ACE2 was associated with more efficient degradation of exogenous ANG II (10(-9) M) in urine from db/db compared with that from db/m mice. Urinary ACE2 could be a potential biomarker of increased metabolism of ANG II in diabetic kidney disease.

  14. Hydronephrosis alters cardiac ACE2 and Mas receptor expression in mice.

    PubMed

    Zhang, Yanling; Ma, Lulu; Wu, Junyan; Chen, Tingting

    2015-06-01

    Hydronephrosis is characterized by substantial loss of tubules and affects renin secretion in the kidney. However, whether alterations of angiotensin-converting enzyme (ACE), ACE2 and Mas receptor in the heart are observed in hydronephrosis is unknown. Thus, we assessed these components in hydronephrotic mice treated with AT1 receptor blockade and ACE inhibitor. Hydronephrosis was induced by left ureteral ligation in Balb/C mice except sham-operated animals. The levels of cardiac ACE, ACE2 and Mas receptor were measured after treatment of losartan or enalapril. Hydronephrosis led to an increase of ACE level and a decrease of ACE2 and Mas receptor in the heart. Losartan decreased cardiac ACE level, but ACE2 and Mas receptor levels significantly increased in hydronephrotic mice (p < 0.01). Enalapril increased ACE2 levels (p < 0.01), but did not affect Mas receptor in the heart. Plasma renin activity (PRA) and Ang II decreased in hydronephrotic mice, but significantly increased after treatment with losartan or enalapril. Hydronephrosis increased cardiac ACE and suppressed ACE2 and Mas receptor levels. AT1 blockade caused sustained activation of cardiac ACE2 and Mas receptor, but ACE inhibitor had the limitation of such activation of Mas receptor in hydronephrotic animals. © The Author(s) 2015.

  15. Macrophage mediated PCI enhanced gene-directed enzyme prodrug therapy

    NASA Astrophysics Data System (ADS)

    Christie, Catherine E.; Zamora, Genesis; Kwon, Young J.; Berg, Kristian; Madsen, Steen J.; Hirschberg, Henry

    2015-03-01

    Photochemical internalization (PCI) is a photodynamic therapy-based approach for improving the delivery of macromolecules and genes into the cell cytosol. Prodrug activating gene therapy (suicide gene therapy) employing the transduction of the E. coli cytosine deaminase (CD) gene into tumor cells, is a promising method. Expression of this gene within the target cell produces an enzyme that converts the nontoxic prodrug, 5-FC, to the toxic metabolite, 5-fluorouracil (5-FU). 5-FC may be particularly suitable for brain tumors, because it can readily cross the bloodbrain barrier (BBB). In addition the bystander effect, where activated drug is exported from the transfected cancer cells into the tumor microenvironment, plays an important role by inhibiting growth of adjacent tumor cells. Tumor-associated macrophages (TAMs) are frequently found in and around glioblastomas. Monocytes or macrophages (Ma) loaded with drugs, nanoparticles or photosensitizers could therefore be used to target tumors by local synthesis of chemo attractive factors. The basic concept is to combine PCI, to enhance the ex vivo transfection of a suicide gene into Ma, employing specially designed core/shell NP as gene carrier.

  16. Lack of association between ACE ID polymorphism and colorectal cancer in Romanian patients.

    PubMed

    Toma, M; Cimponeriu, D; Apostol, P; Stavarachi, M; Cojocaru, M; Belusică, L; Crăciun, A M; Radu, I; Gavrilă, L

    2009-01-01

    The insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene has recently been linked to the pathogenesis of human cancers. The goal of this study was to analyze the possible association between ACE gene I/D polymorphism and colorectal cancer in Romanian patients. Blood samples were obtained, after informed consent, from individuals with colorectal cancer (n=108, M:W = 64:44), and healthy persons (n=150, M:W = 84:66). Genomic DNA was extracted from peripheral blood leucocytes using commercial kits and the insertion (I) / deletion (D) polymorphism was assessed by PCR. Statistical analysis was done using the chi2 test. We determined the odds ratio using the genotype II as risk factor. A p value < 0.05 was considered statistically significant. The distribution of ACE II: ID: DD genotypes was 23.1%: 46.3%: 30.6% in patients and respectively 20%: 48.7%: 31.3% in controls. The distribution of genotype (chi2 0.37, p = 0.54) and alleles (chi2 0.19, p = 0.65) did not differ significantly between cancer patients and control. Study results do not demonstrate an association between ACE ID polymorphism and colorectal cancer in our patients.

  17. Functions of genes and enzymes involved in phenalinolactone biosynthesis.

    PubMed

    Daum, Martina; Schnell, Hans-Jörg; Herrmann, Simone; Günther, Andreas; Murillo, Renato; Müller, Rolf; Bisel, Philippe; Müller, Michael; Bechthold, Andreas

    2010-07-05

    Phenalinolactones are novel terpene glycoside antibiotics produced by Streptomyces sp. Tü6071. Inactivation of three oxygenase genes (plaO2, plaO3 and plaO5), two dehydrogenase genes (plaU, plaZ) and one putative acetyltransferase gene (plaV) led to the production of novel phenalinolactone derivatives (PL HS6, PL HS7, PL HS2 and PL X1). Furthermore, the exact biosynthetic functions of two enzymes were determined, and their in vitro activities were demonstrated. PlaO1, an Fe(II)/alpha-ketoglutarate-dependent dioxygenase, is responsible for the key step in gamma-butyrolactone formation, whereas PlaO5, a cytochrome P450-dependent monooxygenase, catalyses the 1-C-hydroxylation of phenalinolactone D. In addition, stable isotope feeding experiments with biosynthetic precursors shed light on the origin of the carbons in the gamma-butyrolactone moiety.

  18. Evaluating Functional Annotations of Enzymes Using the Gene Ontology.

    PubMed

    Holliday, Gemma L; Davidson, Rebecca; Akiva, Eyal; Babbitt, Patricia C

    2017-01-01

    The Gene Ontology (GO) (Ashburner et al., Nat Genet 25(1):25-29, 2000) is a powerful tool in the informatics arsenal of methods for evaluating annotations in a protein dataset. From identifying the nearest well annotated homologue of a protein of interest to predicting where misannotation has occurred to knowing how confident you can be in the annotations assigned to those proteins is critical. In this chapter we explore what makes an enzyme unique and how we can use GO to infer aspects of protein function based on sequence similarity. These can range from identification of misannotation or other errors in a predicted function to accurate function prediction for an enzyme of entirely unknown function. Although GO annotation applies to any gene products, we focus here a describing our approach for hierarchical classification of enzymes in the Structure-Function Linkage Database (SFLD) (Akiva et al., Nucleic Acids Res 42(Database issue):D521-530, 2014) as a guide for informed utilisation of annotation transfer based on GO terms.

  19. Effects of ACE inhibitors on skeletal muscle.

    PubMed

    Onder, Graziano; Vedova, Cecilia Della; Pahor, Marco

    2006-01-01

    Angiotensin-converting enzyme (ACE) inhibitors reduce morbidity, mortality, hospital admissions, and decline in physical function and exercise capacity in congestive heart failure (CHF) patients. These therapeutic effects are attributed primarily to beneficial cardiovascular actions of these drugs. However, it has been suggested that ACE inhibitor-induced positive effects may also be mediated by direct action on the skeletal muscle. In particular, two recently published observational studies documented that among hypertensive subjects free of CHF, treatment with ACE inhibitors was associated with better performance and muscular outcomes and genetic studies also support the hypothesis that the ACE system may be involved in physical performance and skeletal muscle function. Effects on the skeletal muscle are probably mediated by mechanical, metabolic, anti-inflammatory, nutritional, neurological and angiogenetic actions of these drugs. These studies may have major public health implications for older adults, as consequence of the fact that, in this population, gradual loss of muscle mass and muscle strength can play a key role in the onset and progression of disability. Therefore, if findings of observational studies will be later confirmed in randomized controlled trials, ACE inhibitors could represent an effective intervention to prevent physical decline in the elderly, leading to greater autonomy in this growing population.

  20. Bacteriophage T4 deoxynucleotide kinase: gene cloning and enzyme purification.

    PubMed Central

    Brush, G S; Bhatnagar, S K; Bessman, M J

    1990-01-01

    Gene 1 of bacteriophage T4 has been cloned into a lambda pL expression vector, resulting in the overproduction of deoxynucleotide kinase. A procedure that includes affinity chromatography on Cibacron Blue F3GA-agarose has been used to purify milligram quantities of enzymes from a 2-liter culture. The enzyme has been partially characterized in vitro and in vivo, and it appears to be identical to the deoxynucleotide kinase isolated from T4-infected Escherichia coli. These results prove the earlier contention that the phosphorylation of three dissimilar deoxynucleotides (5-hydroxymethyldeoxycytidylate, dTMP, and dGMP), to the exclusion of most others, is catalyzed by a single protein. Images PMID:2160930

  1. Common variants of ACE contribute to variable age-at-onset of Alzheimer's disease.

    PubMed

    Kehoe, Patrick G; Katzov, Hagit; Andreasen, Niels; Gatz, Maragaret; Wilcock, Gordon K; Cairns, Nigel J; Palmgren, Juni; de Faire, Ulf; Brookes, Anthony J; Pedersen, Nancy L; Blennow, Kaj; Prince, Jonathan A

    2004-04-01

    Studies on the role that genetic variation may play in a complex human disease can be empowered by an assessment of both disease risk in case-control or family models and of quantitative traits that reflect elements of disease etiology. An excellent example of this can be found for the epsilon4 allele of APOE in relation to Alzheimer's disease (AD) for which association with both risk and age-at-onset (AAO) is evident. Following a recent demonstration that variants of the gene encoding angiotensin I converting enzyme ( ACE) contribute to AD risk, we have explored the potential influence of ACE upon AAO in AD. A total of 2861 individuals from three European populations, including six independent AD samples, have been examined in this study. Three single nucleotide polymorphisms (SNPs) previously demonstrated to have maximum effects upon ACE plasma levels and that span the ACE locus were genotyped in these materials. A strong effect upon AAO was observed for marker rs4343 in exon 17 ( P<0.0001), but evidence was also obtained indicating a possible independent effect of marker rs4291 ( P=0.0095) located in the ACE promoter. Effects were consistent with data from previous studies suggesting association with AD in case-control models, whereby alleles demonstrated to confer risk to disease also appear to reduce AAO. Equivalent effects were evident regardless of APOE epsilon4 carrier status and in both males and females. These results provide an important complement to existing AD risk data, confirming that ACE harbors sequence variants that contribute to aspects of AD pathology.

  2. Functional and molecular evidence for expression of the renin angiotensin system and ADAM17-mediated ACE2 shedding in COS7 cells

    PubMed Central

    Grobe, Nadja; Di Fulvio, Mauricio; Kashkari, Nada; Chodavarapu, Harshita; Somineni, Hari K.; Singh, Richa

    2015-01-01

    The renin angiotensin system (RAS) plays a vital role in the regulation of the cardiovascular and renal functions. COS7 is a robust and easily transfectable cell line derived from the kidney of the African green monkey, Cercopithecus aethiops. The aims of this study were to 1) demonstrate the presence of an endogenous and functional RAS in COS7, and 2) investigate the role of a disintegrin and metalloproteinase-17 (ADAM17) in the ectodomain shedding of angiotensin converting enzyme-2 (ACE2). Reverse transcription coupled to gene-specific polymerase chain reaction demonstrated expression of ACE, ACE2, angiotensin II type 1 receptor (AT1R), and renin at the transcript levels in total RNA cell extracts. Western blot and immunohistochemistry identified ACE (60 kDa), ACE2 (75 kDa), AT1R (43 kDa), renin (41 kDa), and ADAM17 (130 kDa) in COS7. At the functional level, a sensitive and selective mass spectrometric approach detected endogenous renin, ACE, and ACE2 activities. ANG-(1–7) formation (m/z 899) from the natural substrate ANG II (m/z 1,046) was detected in lysates and media. COS7 cells stably expressing shRNA constructs directed against endogenous ADAM17 showed reduced ACE2 shedding into the media. This is the first study demonstrating endogenous expression of the RAS and ADAM17 in the widely used COS7 cell line and its utility to study ectodomain shedding of ACE2 mediated by ADAM17 in vitro. The transfectable nature of this cell line makes it an attractive cell model for studying the molecular, functional, and pharmacological properties of the renal RAS. PMID:25740155

  3. Genes and enzymes of ectoine biosynthesis in halotolerant methanotrophs.

    PubMed

    Reshetnikov, Alexander S; Khmelenina, Valentina N; Mustakhimov, Ildar I; Trotsenko, Yuri A

    2011-01-01

    Ectoine (1,4,5,6-tetrahydro-2-methyl-4-pyrimidine carboxylic acid) is a widely distributed compatible solute accumulated by halophilic and halotolerant microorganisms to prevent osmotic stress in highly saline environments. Ectoine as a highly water keeping compound stabilizing biomolecules and whole cells can be used in scientific work, cosmetics, and medicine. Detailed understanding of the organization/regulation of the ectoine biosynthetic pathway in various producers is an active area of research. Here we review current knowledge on some genetic and enzymatic aspects of ectoine biosynthesis in halophilic and halotolerant methanotrophs. By using PCR methodology, the genes coding for the specific enzymes of ectoine biosynthesis, diaminobutyric acid (DABA) aminotransferase (EctB), DABA acetyltransferase (EctA), and ectoine synthase (EctC), were identified in several methanotrophic species. Organization of these genes in either ectABC or ectABC-ask operons, the latter additionally encoding aspartate kinase isozyme (Ask), correlated well with methanotroph halotolerance and intracellular ectoine level. A new gene, ectR1 encoding the MarR-like transcriptional regulatory protein EctR1, negatively controlling transcription of ectoine biosynthetic genes was found upstream of ectABC-ask operon in Methylomicrobium alcaliphilum 20Z. The ectR-like genes were also found in halotolerant methanol utilizers Methylophaga alcalica and Methylophaga thalassica as well as in several genomes of nonmethylotrophic species. The His(6)-tagged DABA acetyltransferases from Mm. alcaliphilum, M. alcalica, and M. thalassica were purified and the enzyme properties were found to correlate with the ecophysiologies of these bacteria. All these discoveries should be very helpful for better understanding the biosynthetic mechanism of this important natural compound, and for the targeted metabolic engineering of its producers.

  4. Necessity of angiotensin-converting enzyme-related gene for cardiac functions and longevity of Drosophila melanogaster assessed by optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Liao, Fang-Tsu; Chang, Cheng-Yi; Su, Ming-Tsan; Kuo, Wen-Chuan

    2014-01-01

    Prior studies have established the necessity of an angiotensin-converting enzyme-related (ACER) gene for heart morphogenesis of Drosophila. Nevertheless, the physiology of ACER has yet to be comprehensively understood. Herein, we employed RNA interference to down-regulate the expression of ACER in Drosophila's heart and swept source optical coherence tomography to assess whether ACER is required for cardiac functions in living adult flies. Several contractile parameters of Drosophila heart, including the heart rate (HR), end-diastolic diameter (EDD), end-systolic diameter (ESD), percent fractional shortening (%FS), and stress-induced cardiac performance, are shown, which are age dependent. These age-dependent cardiac functions declined significantly when ACER was down-regulated. Moreover, the lifespans of ACER knock-down flies were significantly shorter than those of wild-type control flies. Thus, we posit that ACER, the Drosophila ortholog of mammalian angiotensin-converting enzyme 2 (ACE2), is essential for both heart physiology and longevity of animals. Since mammalian ACE2 controls many cardiovascular physiological features and is implicated in cardiomyopathies, our findings that ACER plays conserved roles in genetically tractable animals will pave the way for uncovering the genetic pathway that controls the renin-angiotensin system.

  5. Alteration of cardiac ACE2/Mas expression and cardiac remodelling in rats with aortic constriction.

    PubMed

    Zhang, Yanling; Li, Bing; Wang, Bingxiangi; Zhang, Jingjun; Wu, Junyan; Morgan, Trefor

    2014-12-31

    The recent discovery of the new components of the renin-angiotensin system (RAS) suggests the importance of the maintenance of cardiovascular structure and functions. To assess the role of the angiotensin-converting enzyme 2 (ACE2)-Mas receptor axis in the regulation of cardiac structure and function, the present work investigated the expression of ACE2 and Mas receptor in the heart in the cardiac remodeling that occurs in aortic constricted rats. Partial abdominal aortic ligation was carried out in Sprague-Dawley rats. Angiotensin AT1 receptor blockade and ACE inhibition were achieved by losartan and enalapril treatment, respectively. Results showed that aortic constriction increased left ventricular hypertrophy, fibrosis, mean arterial pressure (MAP), plasma renin activity (PRA) and cardiac ACE levels, but decreased the expression of cardiac ACE2 and Mas receptor. Losartan treatment significantly decreased MAP, left ventricle hypertrophy (LVH), fibrosis, and increased cardiac ACE2 and Mas expression. Enalapril also improved the cardiac parameters with a rise in cardiac ACE2, but did not change the Mas level. In conclusion, aortic constriction results in cardiac hypertrophy, fibrosis and a rise of cardiac ACE expression. Both AT1 receptor blocker and ACE inhibitor play a cardioprotective role in aortic constriction. However, AT1 receptor blocker particularly promotes cardiac ACE2 and Mas receptor levels. ACE inhibitor is associated with the inhibition of ACE and normalization of cardiac ACE2 activity.

  6. Radiation Exposure Alters Expression of Metabolic Enzyme Genes In Mice

    NASA Technical Reports Server (NTRS)

    Wotring, Virginia E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2010-01-01

    Most pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Because of the importance of the liver in drug metabolism it is important to understand the effects of spaceflight on the enzymes of the liver. Exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. This study is an effort to examine the effects of adaptive mechanisms that may be triggered by early exposure to low radiation doses. Using procedures approved by the JSC Animal Care & Use Committee, C57 male mice were exposed to Cs-137 in groups: controls, low dose (50 mGy), high dose (6Gy) and a fourth group that received both radiation doses separated by 24 hours. Animals were anesthetized and sacrificed 4 hours after their last radiation exposure. Livers were removed immediately and flash-frozen in liquid nitrogen. Tissue was homogenized, RNA extracted and purified (Absolutely RNA, Agilent). Quality of RNA samples was evaluated (Agilent Bioanalyzer 2100). Complementary DNA was prepared from high-quality RNA samples, and used to run RT-qPCR screening arrays for DNA Repair and Drug Metabolism (SuperArray, SABiosciences/Qiagen; BioRad Cfx96 qPCR System). Of 91 drug metabolism genes examined, expression of 7 was altered by at least one treatment condition. Genes that had elevated expression include those that metabolize promethazine and steroids (4-8-fold), many that reduce oxidation products, and one that reduces heavy metal exposure (greater than 200-fold). Of the 91 DNA repair and general metabolism genes examined, expression of 14 was altered by at least one treatment condition. These gene expression changes are likely homeostatic and could lead to development of new radioprotective countermeasures.

  7. ACES program - Lessons learned

    NASA Technical Reports Server (NTRS)

    Jones, Victoria L.; Rice, Sally C.; Waites, Henry B.

    1988-01-01

    The ACES Program involved the experimental evaluation of three LSS (large space structures) control design techniques at the LSS GTF (ground test facility) at NASA/MSFC. The three techniques were developed under the ACOSS (active control of space structures) Program specifically for application to LSS. The techniques included FAMESS (filter accommodated model error sensitivity suppression), HAC/LAC (high authority control/low authority control), and positivity. Some of the lessons that have been learned during the course of the ACES program are examined.

  8. ACE-1 experiment

    NASA Image and Video Library

    2013-06-24

    ISS036-E-019830 (24 June 2013) --- In the International Space Station’s Destiny laboratory, NASA astronaut Karen Nyberg, Expedition 36 flight engineer, speaks into a microphone while conducting a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

  9. ACE-1 experiment

    NASA Image and Video Library

    2013-06-24

    ISS036-E-019783 (24 June 2013) --- In the International Space Station’s Destiny laboratory, a fisheye lens attached to an electronic still camera was used to capture this image of NASA astronaut Karen Nyberg, Expedition 36 flight engineer, as she conducts a session with the Advanced Colloids Experiment (ACE)-1 sample preparation at the Light Microscopy Module (LMM) in the Fluids Integrated Rack / Fluids Combustion Facility (FIR/FCF). ACE-1 is a series of microscopic imaging investigations that uses the microgravity environment to examine flow characteristics and the evolution and ordering effects within a group of colloidal materials.

  10. ACE2 and Microbiota: Emerging Targets for Cardiopulmonary Disease Therapy.

    PubMed

    Cole-Jeffrey, Colleen T; Liu, Meng; Katovich, Michael J; Raizada, Mohan K; Shenoy, Vinayak

    2015-12-01

    The health of the cardiovascular and pulmonary systems is inextricably linked to the renin-angiotensin system (RAS). Physiologically speaking, a balance between the vasodeleterious (Angiotensin-converting enzyme [ACE]/Angiotensin II [Ang II]/Ang II type 1 receptor [AT1R]) and vasoprotective (Angiotensin-converting enzyme 2 [ACE2]/Angiotensin-(1-7) [Ang-(1-7)]/Mas receptor [MasR]) components of the RAS is critical for cardiopulmonary homeostasis. Upregulation of the ACE/Ang II/AT1R axis shifts the system toward vasoconstriction, proliferation, hypertrophy, inflammation, and fibrosis, all factors that contribute to the development and progression of cardiopulmonary diseases. Conversely, stimulation of the vasoprotective ACE2/Ang-(1-7)/MasR axis produces a counter-regulatory response that promotes cardiovascular health. Current research is investigating novel strategies to augment actions of the vasoprotective RAS components, particularly ACE2, in order to treat various pathologies. Although multiple approaches to increase the activity of ACE2 have displayed beneficial effects against experimental disease models, the mechanisms behind its protective actions remain incompletely understood. Recent work demonstrating a non-catalytic role for ACE2 in amino acid transport in the gut has led us to speculate that the therapeutic effects of ACE2 can be mediated, in part, by its actions on the gastrointestinal tract and/or gut microbiome. This is consistent with emerging data which suggest that dysbiosis of the gut and lung microbiomes is associated with cardiopulmonary disease. This review highlights new developments in the protective actions of ACE2 against cardiopulmonary disorders, discusses innovative approaches to targeting ACE2 for therapy, and explores an evolving role for gut and lung microbiota in cardiopulmonary health.

  11. Microbial sucrose isomerases: producing organisms, genes and enzymes.

    PubMed

    Goulter, Ken C; Hashimi, Saeed M; Birch, Robert G

    2012-01-05

    Sucrose isomerase (SI) activity is used industrially for the conversion of sucrose into isomers, particularly isomaltulose or trehalulose, which have properties advantageous over sucrose for some food uses. All of the known microbial SIs are TIM barrel proteins that convert sucrose without need for any cofactors, with varying kinetics and product specificities. The current analysis was undertaken to bridge key gaps between the information in patents and scientific publications about the microbes and enzymes useful for sucrose isomer production. This analysis shows that microbial SIs can be considered in 5 structural classes with corresponding functional distinctions that broadly align with the taxonomic differences between producing organisms. The most widely used bacterial strain for industrial production of isomaltulose, widely referred to as "Protaminobacter rubrum" CBS 574.77, is identified as Serratia plymuthica. The strain producing the most structurally divergent SI, with a high product specificity for trehalulose, widely referred to as "Pseudomonas mesoacidophila" MX-45, is identified as Rhizobium sp. Each tested SI-producer is shown to have a single SI gene and enzyme, so the properties reported previously for the isolated proteins can reasonably be associated with the products of the genes subsequently cloned from the same isolates and SI classes. Some natural isolates with potent SI activity do not catabolize the isomer under usual production conditions. The results indicate that their industrial potential may be further enhanced by selection for variants that do not catabolize the sucrose substrate.

  12. Enzyme diversity and mosaic gene organization in denitrification.

    PubMed

    Zumft, W G; Körner, H

    1997-02-01

    Denitrification is a main branch of the global nitrogen cycle. In the past ten years unravelling the underlying biochemistry and genetics has proceeded at an increasing pace. Fungal denitrification has become a new field. The biochemical investigation of denitrification has culminated in the description of the crystal structures of the two types of nitrite reductases. The N2O reductase shares with cytochrome c oxidase the CuA center as a structurally novel metal site. The cytochrome b subunit of NO reductase has a striking conservation of heme-binding transmembrane segments versus the subunit I of cytochrome c oxidase. Another putative denitrification gene product shows structural relation to the subunit III of the oxidase. N2O reductase and NO reductase may be ancestors of energy-conserving enzymes of the heme-copper oxidase superfamily. More than 30 genes for denitrification are located in a > 30-kb cluster in Pseudomonas stutzeri, and comparable gene clusters have been identified in Pseudomonas aeruginosa and Paracoccus denitrificans. Genes necessary for nitrite reduction and NO reduction have a mosaic arrangement with very few conserved locations within these clusters and relative to each other.

  13. Hepatocyte Growth Factor Regulates Angiotensin Converting Enzyme Expression*

    PubMed Central

    Day, Regina M.; Thiel, Gerald; Lum, Julie; Chévere, Rubén D.; Yang, Yongzhen; Stevens, Joanne; Sibert, Laura; Fanburg, Barry L.

    2008-01-01

    Hepatocyte growth factor (HGF) is a mitogen, morphogen, and motogen that functions in tissue healing and acts as an anti-fibrotic factor. The mechanism for this is not well understood. Recent studies implicate somatic angiotensin-converting enzyme (ACE) in fibrosis. We examined the effects of HGF on ACE expression in bovine pulmonary artery endothelial cells (BPAEC). Short term treatment of BPAEC with HGF transiently increased both ACE mRNA (3 h) and activity (24 h), as determined by ACE protease assays and reverse transcription-PCR. Incubation of BPAEC with HGF for longer periods suppressed ACE mRNA (6 h) and activity (72 h). In contrast, phorbol ester (PMA) treatment produced sustained increase in ACE mRNA and activity. We examined the short term molecular effects of HGF on ACE using PMA for comparison. HGF and PMA increased transcription from a luciferase reporter with the core ACE promoter, which contains a composite binding site for SP1/3 and Egr-1. Immunocytochemistry and electrophoretic mobility shift assay showed that both HGF and PMA increased Egr-1 binding. HGF also increased SP3 binding, as measured by EMSA. However, HGF and PMA increased the cellular activity of only Egr-1, not SP3, as measured by luciferase reporter assays. Deletion of the Egr-1 site in the reporter construct completely abrogated HGF-induced transcription but only ~50% of PMA-induced activity. Expression of dominant negative Egr-1 and SP3 blocked up-regulation of the ACE promoter by HGF but only reduced up-regulation by PMA. These results show that HGF transiently increases gene transcription of ACE via activation of Egr-1, whereas PMA regulation involves Egr-1 and additional factor(s). PMID:14679188

  14. Evaluation of Bacillus subtilis SPB1 biosurfactant effects on hyperglycemia, angiotensin I-converting enzyme (ACE) activity and kidney function in rats fed on high-fat-high-fructose diet.

    PubMed

    Zouari, Raida; Hamden, Khaled; El Feki, Abdelfattah; Chaabouni, Khansa; Makni-Ayadi, Fatma; Sallemi, Fahima; Ellouze-Chaabouni, Semia; Ghribi-Aydi, Dhouha

    2017-05-01

    This study investigated the protective and the curative effects of Bacillus subtilis SPB1 crude lipopeptide biosurfactant in alleviating induced obesity complications in rats fed on high-fat-high-fructose diet (HFFD). Male Wistar rats were divided into five groups with the following treatment schedule: normal diet-fed rats (CD), HFFD-fed rats, HFFD-fed rats supplemented with SPB1 biosurfactant from the first day of the experiment (HFFD + Bios1), rats fed on HFFD receiving standard drug (HFFD + Torva), or SPB1 biosurfactant (HFFD + Bios2) during the last 4 weeks of the study. HFFD induced hyperglycemia, manifested by a significant (p < 0.001) increase (20%) in the levels of glucose and α-amylase activity in the plasma, when compared with CD. The administration of SPB1 biosurfactant to rats fed on HFFD reverted back normal blood glucose and α-amylase activity levels. Also, the findings clearly showed that acute oral administration of SPB1 biosurfactant reduced significantly (34%) the peak of blood glucose concentration 60 min after glucose administration, as compared with untreated rats fed on HFFD. Furthermore, renal dysfunction indices such as creatinine and urea as well as the level of angiotensin I-converting enzyme (ACE) exhibited remarkable increases in serum of rats fed on HFFD by 28.35%, 46%, and 92%,. Interestingly, SPB1 lipopeptides treatments decreased the creatinine and urea levels significantly (p < 0.001) near normal values, as compared with that of the HFFD group, and also showed an improvement of the kidney cortex architecture. Moreover, SPB1 biosurfactant displayed a potent inhibition of ACE activity in vitro (CI50  value= 1.37 mg/mL) as well as in vivo in obese rats by 42% and 27.25% with HFFD + Bios1 and HFFD + Bios2 treatments, respectively, and comparatively with the HFFD group. Besides, SPB1 lipopeptides treatments improved some of serum electrolytes such as Na(+), K(+), Ca(2+ ), and Mg(2+). The results

  15. ACE inhibition with captopril retards the development of signs of neurodegeneration in an animal model of Alzheimer's disease.

    PubMed

    AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula

    2013-08-16

    Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer's disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration.

  16. Inhibition of MAPK-mediated ACE expression by compound C66 prevents STZ-induced diabetic nephropathy.

    PubMed

    Pan, Yong; Huang, Yi; Wang, Zhe; Fang, Qilu; Sun, Yusheng; Tong, Chao; Peng, Kesong; Wang, Yangwei; Miao, Lining; Cai, Lu; Zhao, Yunjie; Liang, Guang

    2014-02-01

    A range of in vitro, experimental and clinical intervention studies have implicated an important role for hyperglycaemia-induced activation of the renin-angiotensin system (RAS) in the development and progression of diabetic nephropathy (DN). Blockade of RAS by angiotensin converting enzyme (ACE) inhibitors is an effective strategy in treating diabetic kidney diseases. However, few studies demonstrate the mechanism by which hyperglycaemia up-regulates the expression of ACE gene. Our previous studies have identified a novel curcumin analogue, (2E,6E)-2,6-bis(2-(trifluoromethyl)benzylidene)cyclohexanone (C66), which could inhibit the high glucose (HG)-induced phosphorylation of mitogen-activated protein kinases in mouse macrophages. In this study, we found that the renal protection of C66 in diabetic mice was associated with mitogen-activated protein kinase (MAPK) inactivation and ACE/angiotensin II (Ang II) down-regulation. Generally, MAPKs have been considered as a downstream signalling of Ang II and a mediator for Ang II-induced pathophysiological actions. However, using C66 and specific inhibitors as small molecule probes, in vitro experiments demonstrate that the MAPK signalling pathway regulates ACE expression under HG stimulation, which contributes to renal Ang II activation and the development of DN. This study indicates that C66 is a potential candidate of DN therapeutic agents, and more importantly, that reduction in ACE expression by MAPKs inhibition seems to be an alternative strategy for the treatment of DN.

  17. ACE Inhibition with Captopril Retards the Development of Signs of Neurodegeneration in an Animal Model of Alzheimer’s Disease

    PubMed Central

    AbdAlla, Said; Langer, Andreas; Fu, Xuebin; Quitterer, Ursula

    2013-01-01

    Increased generation of reactive oxygen species (ROS) is a significant pathological feature in the brains of patients with Alzheimer’s disease (AD). Experimental evidence indicates that inhibition of brain ROS could be beneficial in slowing the neurodegenerative process triggered by amyloid-beta (Abeta) aggregates. The angiotensin II AT1 receptor is a significant source of brain ROS, and AD patients have an increased brain angiotensin-converting enzyme (ACE) level, which could account for an excessive angiotensin-dependent AT1-induced ROS generation. Therefore, we analyzed the impact of ACE inhibition on signs of neurodegeneration of aged Tg2576 mice as a transgenic animal model of AD. Whole genome microarray gene expression profiling and biochemical analyses demonstrated that the centrally active ACE inhibitor captopril normalized the excessive hippocampal ACE activity of AD mice. Concomitantly, the development of signs of neurodegeneration was retarded by six months of captopril treatment. The neuroprotective profile triggered by captopril was accompanied by reduced amyloidogenic processing of the amyloid precursor protein (APP), and decreased hippocampal ROS, which is known to enhance Abeta generation by increased activation of beta- and gamma-secretases. Taken together, our data present strong evidence that ACE inhibition with a widely used cardiovascular drug could interfere with Abeta-dependent neurodegeneration. PMID:23959119

  18. Vascular Wall ACE is not required for Atherogenesis in ApoE-/- mice

    PubMed Central

    Weiss, Daiana; Bernstein, Kenneth E.; Fuchs, Sebastian; Adams, Jonathan; Synetos, Andreas; Taylor, W. Robert

    2009-01-01

    Background It has been proposed that elements of the renin angiotensin system expressed in the arterial wall are critical for the development of atherosclerosis. Angiotensin converting enzyme (ACE) is highly expressed by the endothelium and is responsible for a critical enzymatic step in the generation of angiotensin II. However, the functional contribution of ACE expression in the vascular wall in atherogenesis is unknown. Therefore, we made use of unique genetic models in which mice without expression of ACE in the vascular wall were crossed with apoE-/- mice in order to determine the contribution of tissue ACE expression to atherosclerotic lesion formation. Methods and Results Mice expressing either a soluble form of ACE (ACE 2/2) or mice with somatic ACE expression restricted to the liver and kidney (ACE 3/3) on an ApoE-/- background were placed on a standard chow or Western diet for 6 months. Atherosclerotic lesion area in the ACE 2/2 mice was significantly lower than that seen in the ACE 3/3 mice. However, these animals also had significantly lower blood pressure and reduced plasma ACE activity which precluded establishing a specific causal relationship between absent tissue ACE activity and decreased atherosclerotic lesion extent. Therefore, we studied the ACE 3/3 mice which are normotensive and lack vascular ACE expression. In the ACE 3/3 animals, atherosclerotic lesion area was no different from wild type controls despite reduced plasma ACE activity. Conclusions We concluded that under these experimental conditions, expression of ACE in the arterial wall is not required for atherosclerotic lesion formation. PMID:19880118

  19. Insulin treatment attenuates renal ADAM17 and ACE2 shedding in diabetic Akita mice.

    PubMed

    Salem, Esam S B; Grobe, Nadja; Elased, Khalid M

    2014-03-15

    Angiotensin-converting enzyme 2 (ACE2) is located in several tissues and is highly expressed in renal proximal tubules, where it degrades the vasoconstrictor angiotensin II (ANG II) to ANG-(1-7). Accumulating evidence supports protective roles of ACE2 in several disease states, including diabetic nephropathy. A disintegrin and metalloprotease (ADAM) 17 is involved in the shedding of several transmembrane proteins, including ACE2. Our previous studies showed increased renal ACE2, ADAM17 expression, and urinary ACE2 in type 2 diabetic mice (Chodavarapu H, Grobe N, Somineni HK, Salem ES, Madhu M, Elased KM. PLoS One 8: e62833, 2013). The aim of the present study was to determine the effect of insulin on ACE2 shedding and ADAM17 in type 1 diabetic Akita mice. Results demonstrate increased renal ACE2 and ADAM17 expression and increased urinary ACE2 fragments (≈70 kDa) and albumin excretion in diabetic Akita mice. Immunostaining revealed colocalization of ACE2 with ADAM17 in renal tubules. Renal proximal tubular cells treated with ADAM17 inhibitor showed reduced ACE2 shedding into the media, confirming ADAM17-mediated shedding of ACE2. Treatment of Akita mice with insulin implants for 20 wk normalized hyperglycemia and decreased urinary ACE2 and albumin excretion. Insulin also normalized renal ACE2 and ADAM17 but had no effect on tissue inhibitor of metalloproteinase 3 (TIMP3) protein expression. There was a positive linear correlation between urinary ACE2 and albuminuria, blood glucose, plasma creatinine, glucagon, and triglycerides. This is the first report showing an association between hyperglycemia, cardiovascular risk factors, and increased shedding of urinary ACE2 in diabetic Akita mice. Urinary ACE2 could be used as a biomarker for diabetic nephropathy and as an index of intrarenal ACE2 status.

  20. Effects of ACE inhibitors on cardiac angiotensin II and aldosterone in humans: "Relevance of lipophilicity and affinity for ACE".

    PubMed

    Ruzicka, Marcel; Coletta, Elizabeth; White, Roselyn; Davies, Ross; Haddad, Haissam; Leenen, Frans H H

    2010-11-01

    Angiotensin-converting enzyme (ACE) inhibitors differ in their lipophilic/hydrophilic index that determines their tissue bioavailability and affinity to ACE, which may result in major differences in the degree of blockade of cardiac ACE. We evaluated the hypothesis that in patients with chronic heart failure (CHF) and activated cardiac renin-angiotensin-aldosterone system (RAAS), lipophilic ACE inhibitors with high affinity for ACE (perindopril and quinapril) will cause marked blockade of cardiac angiotensin (Ang) II and aldosterone generation, but not a hydrophilic ACE inhibitor with low affinity for ACE (lisinopril). Patients were randomized to receive perindopril (8 mg/day), quinapril (40 mg/day), or lisinopril (20 mg/day) for 3-4 weeks before cardiac catheterization. The coronary sinus-aortic root gradients for Ang I and II, and aldosterone were determined. A total of 19 patients completed the study. Compared to a healthy control group, all three ACE inhibitors decreased circulating Ang II and aldosterone to a similar extent. There were only minor differences between the three ACE inhibitors for the Ang II gradient between the coronary sinus and aortic root. The gradient for aldosterone tended to be positive in the quinapril group and absent/negative in the lisinopril and perindopril groups. Despite the lowest pulmonary capillary wedge pressure (PCWP), gradients between the coronary sinus and aortic root for Ang II and aldosterone were actually the highest in the quinapril group. These findings do not support the concept that a hydrophilic ACE inhibitor is less effective in blocking the cardiac RAAS as compared to lipophilic ACE inhibitors.

  1. ACES--Today and Tomorrow.

    ERIC Educational Resources Information Center

    Hackney, Harold

    1991-01-01

    Presents text of Presidential Address delivered March 24, 1991, at the Association for Counselor Education and Supervision (ACES) luncheon, part of the American Association for Counseling and Development Convention held in Reno, Nevada. Comments on past, present, and future of ACES, particularly on future challenges and role of ACES. (ABL)

  2. Enzyme

    MedlinePlus

    Enzymes are complex proteins that cause a specific chemical change in all parts of the body. For ... use them. Blood clotting is another example of enzymes at work. Enzymes are needed for all body ...

  3. Renal angiotensin-converting enzyme and blood pressure control

    PubMed Central

    Bernstein, Kenneth E.; Giani, Jorge F.; Shen, Xiao Z.; Gonzalez-Villalobos, Romer A.

    2014-01-01

    Purpose of review This review presents novel findings regarding the renal angiotensin-converting enzyme (ACE) and its role in blood pressure (BP) control. Recent findings The textbook flow diagram of the renin–angiotensin system (RAS) shows the pulmonary endothelium as the main source of the ACE that converts angiotensin I to angiotensin II. However, ACE is made in large quantities by the kidneys, which raises the important question of what precisely is the function of renal ACE? Recent studies in gene-targeted mice indicates that renal ACE plays a dominant role in regulating the response of the kidney to experimental hypertension. In particular, renal ACE and locally generated angiotensin II affect the activity of several key sodium transporters and the induction of sodium and water retention resulting in the elevation of BP. Summary New experimental data link the renal ACE/angiotensin II pathway and the local regulation of sodium transport as key elements in the development of hypertension. PMID:24378774

  4. Amyloid-β-related genes SORL1 and ACE are genetically associated with risk for late-onset Alzheimer disease in the Chinese population.

    PubMed

    Ning, Mei; Yang, Yifeng; Zhang, Zhou; Chen, Zhuo; Zhao, Teng; Zhang, Di; Zhou, Daizhan; Xu, Jie; Liu, Zhe; Wang, Yabing; Liu, Yun; Zhao, Xinzhi; Li, Weidong; Li, Sheng; He, Lin

    2010-01-01

    Late-onset Alzheimer Disease (LOAD) is a common neurodegenerative disease, and one of its major pathologic characteristics is senile plaques. Proteins encoded by SORL1 and ACE have been shown to be related to the processing, trafficking, and degradation of Amyloid-β, the principal component of senile plaques. In this paper, we investigated whether SORL1 and ACE are associated with LOAD. We recruited 144 LOAD patients and 476 controls from Shanghai, China and conducted a case-control study on 9 single-nucleotide polymorphisms (SNPs): 6 in SORL1 (rs2070045, rs661057, rs668387, rs689021, rs3824968, rs2282649) and 3 in ACE (rs1800764, rs4343, rs1799752). Despite the small case sample size (144), we observed that rs1800764, rs4343, rs1799752 in ACE, and rs2070045, rs3824968, rs2282649 in SORL1 showed significantly different allele frequencies between patients and controls (P=4.57×10, 5.24×10, 1.95×10, 1.77×10, 6.44×10, and 3.11×10, respectively). Moreover, haplotypes on ACE and on SORL1 were significantly associated with LOAD (all P-value<0.009 in ACE and all P-value <0.003 in SORL1). In ACE, we found the most significant protective haplotype encompasses SNPs rs2070045, rs3824968, and rs2282649 (C-G-D: OR=0.20, P=8.96×10). In SORL1, we detected a "complementary" haplotype (G-A-T: OR=1.54, P=2.67×10; T-T-C: OR=0.63, P=2.36×10) composed of SNPs rs2070045, rs3824968, and rs2282649. In addition, we carried out meta-analysis with 3 other Asian populations on 3 SNPs in SORL1 (rs2070045, rs3824968, and rs2282649). Results supported our initial finding that these 3 SNPs were associated with LOAD. Our data suggested that SORL1 and ACE might play a role in LOAD susceptibility among Han Chinese.

  5. Sequences and expression of pyruvate dehydrogenase genes from Pseudomonas aeruginosa.

    PubMed Central

    Rae, J L; Cutfield, J F; Lamont, I L

    1997-01-01

    A mutant of Pseudomonas aeruginosa, OT2100, which appeared to be defective in the production of the fluorescent yellow-green siderophore pyoverdine had been isolated previously following transposon mutagenesis (T. R. Merriman and I. L. Lamont, Gene 126:17-23, 1993). DNA from either side of the transposon insertion site was cloned, and the sequence was determined. The mutated gene had strong identity with the dihydrolipoamide acetyltransferase (E2) components of pyruvate dehydrogenase (PDH) from other bacterial species. Enzyme assays revealed that the mutant was defective in the E2 subunit of PDH, preventing assembly of a functional complex. PDH activity in OT2100 cell extracts was restored when extract from an E1 mutant was added. On the basis of this evidence, OT2100 was identified as an aceB or E2 mutant. A second gene, aceA, which is likely to encode the E1 component of PDH, was identified upstream from aceB. Transcriptional analysis revealed that aceA and aceB are expressed as a 5-kb polycistronic transcript from a promoter upstream of aceA. An intergenic region of 146 bp was located between aceA and aceB, and a 2-kb aceB transcript that originated from a promoter in the intergenic region was identified. DNA fragments upstream of aceA and aceB were shown to have promoter activities in P. aeruginosa, although only the aceA promoter was active in Escherichia coli. It is likely that the apparent pyoverdine-deficient phenotype of mutant OT2100 is a consequence of acidification of the growth medium due to accumulation of pyruvic acid in the absence of functional PDH. PMID:9171401

  6. Circulating ACE2 activity correlates with cardiovascular disease development.

    PubMed

    Úri, Katalin; Fagyas, Miklós; Kertész, Attila; Borbély, Attila; Jenei, Csaba; Bene, Orsolya; Csanádi, Zoltán; Paulus, Walter J; Édes, István; Papp, Zoltán; Tóth, Attila; Lizanecz, Erzsébet

    2016-10-01

    It was shown recently that angiotensin-converting enzyme activity is limited by endogenous inhibition in vivo, highlighting the importance of angiotensin II (ACE2) elimination. The potential contribution of the ACE2 to cardiovascular disease progression was addressed. Serum ACE2 activities were measured in different clinical states (healthy, n=45; hypertensive, n=239; heart failure (HF) with reduced ejection fraction (HFrEF) n=141 and HF with preserved ejection fraction (HFpEF) n=47). ACE2 activity was significantly higher in hypertensive patients (24.8±0.8 U/ml) than that in healthy volunteers (16.2±0.8 U/ml, p=0.01). ACE2 activity further increased in HFrEF patients (43.9±2.1 U/ml, p=0.001) but not in HFpEF patients (24.6±1.9 U/ml) when compared with hypertensive patients. Serum ACE2 activity negatively correlated with left ventricular systolic function in HFrEF, but not in hypertensive, HFpEF or healthy populations. Serum ACE2 activity had a fair diagnostic value to differentiate HFpEF from HFrEF patients in this study. Serum ACE2 activity correlates with cardiovascular disease development: it increases when hypertension develops and further increases when the cardiovascular disease further progresses to systolic dysfunction, suggesting that ACE2 metabolism plays a role in these processes. In contrast, serum ACE2 activity does not change when hypertension progresses to HFpEF, suggesting a different pathomechanism for HFpEF, and proposing a biomarker-based identification of these HF forms. © The Author(s) 2016.

  7. Cardiac protective effects of irbesartan via the PPAR-gamma signaling pathway in angiotensin-converting enzyme 2-deficient mice.

    PubMed

    Zhang, Zhen-Zhou; Shang, Qian-Hui; Jin, Hai-Yan; Song, Bei; Oudit, Gavin Y; Lu, Lin; Zhou, Tong; Xu, Ying-Le; Gao, Ping-Jin; Zhu, Ding-Liang; Penninger, Josef M; Zhong, Jiu-Chang

    2013-09-25

    Angiotensin-converting enzyme 2 (ACE2), a monocarboxypeptidase which metabolizes angiotensin II (Ang II) to generate Ang-(1-7), has been shown to prevent cardiac hypertrophy and injury but the mechanism remains elusive. Irbesartan has the dual actions of angiotensin receptor blockade and peroxisome proliferator-activated receptor-γ (PPARγ) activation. We hypothesized that irbesartan would exert its protective effects on ACE2 deficiency-mediated myocardial fibrosis and cardiac injury via the PPARγ signaling. 10-week-old ACE2 knockout (ACE2KO; Ace2(-/y)) mice received daily with irbesartan (50 mg/kg) or saline for 2 weeks. The wild-type mice (Ace2(+/y)) were used to the normal controls. We examined changes in myocardial ultrastructure, fibrosis-related genes and pathological signaling by real-time PCR gene array, Western blotting, Masson trichrome staining and transmission electron microscope analyses, respectively. Compared with the Ace2(+/y) mice, cardiac expression of PPARα and PPARγ were reduced in Ace2(-/y) mice and the myocardial collagen volume fraction (CVF) and expression of fibrosis-related genes were increased, including transforming growth factor-β1 (TGFβ1), connective tissue growth factor (CTGF), collagen I and collagen III. Moreover, ACE2 deficiency triggered cardiac hypertrophy, increased myocardial fibrosis and adverse ultrastructure injury in ACE2KO hearts with higher levels of atrial natriuretic factor (ANF) and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2), without affecting cardiac systolic function. Intriguingly, treatment with irbesartan significantly reversed ACE2 deficiency-mediated pathological hypertrophy and myocardial fibrosis in Ace2(-/y) mice linked with enhancement of plasma Ang-(1-7) level and downregulation of AT1 receptor in heart. Consistent with attenuation of myocardial fibrosis and ultrastructure injury, the myocardial CVF and levels of ANF, TGFβ1, CTGF, collagen I, collagen III and phosphorylated ERK1

  8. Effects of human endothelial gene polymorphisms on cellular responses to hyperglycaemia: role of NOS3 (Glu298Asp) and ACE (I/D) polymorphisms.

    PubMed

    Joshi, Mandar S; Wattanapitayakul, Suvara; Schanbacher, Brandon L; Bauer, John A

    2011-10-01

    The functional relevance of NOS3 and ACE genetic variations to endothelial cell function is largely unstudied. Here we tested the functional relevance of the NOS3 (Glu298Asp) polymorphism and ACE (I/D) polymorphism in endothelial cells in vitro. Our hypothesis was that these genetic polymorphisms alter endothelial cell sensitivity to glucose and 3-nitrotyrosine (3NT). Genotyped HUVECs were incubated with glucose, free 3NT or a combination of these two toxicants. Significant differences in glucose-induced cell death and free 3NT-induced cell death were observed among the NOS3 genotypes. Combined glucose/3NT caused increased toxicity among the NOS3 genotypes. No differences were observed among the ACE genotypes in their responses to glucose/3NT. These data demonstrate that the NOS3 genotype may be an important predictor of, or be mechanistically involved in, endothelial vulnerability, whereas the ACE I/D genotype is apparently less important. Thus this NOS3 genetic variation may play a role in vulnerability to endothelium-dependent diabetic vascular complications.

  9. The role of angiotensin-converting enzyme polymorphism in congestive heart failure.

    PubMed

    Pilati, Mara; Cicoira, Mariantonietta; Zanolla, Luisa; Nicoletti, Ilaria; Muraglia, Simone; Zardini, Piero

    2004-01-01

    Angiotensin-converting enzyme (ACE) is a zinc metallopeptidase, with primary known functions of converting angiotensin I into the vasoactive and aldosterone-stimulating peptide angiotensin II and inactivating bradykinin. There is high variability among individuals in ACE concentrations, mainly due to the presence of a genetic polymorphism. The ACE gene has, in fact, insertion/deletion polymorphism in intron 16, consisting of a 287-base pair Alu repeat sequence, with three genotypes: insertion polymorphism, insertion/deletion polymorphism, and deletion polymorphism. The genetic effect accounts for 47% of the total variance of serum ACE. The determination of this polymorphism has allowed researchers to study the implications of the ACE gene in many case-control studies of cardiovascular disease, including myocardial infarction and hypertrophic and dilated cardiomyopathy. We review the current knowledge about the ACE gene polymorphism and its implications in heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Interpretation of the results of studies about the role of this polymorphism are controversial. The repetition of epidemio-genetic studies and the creation of adequate experimental studies will help to definitively establish the pathogenetic role of the permanent increase in ACE expression associated with the deletion polymorphism genotype.

  10. ACE-II genotype and I allele predicts ischemic stroke among males in south India

    PubMed Central

    Vijayan, Murali; Chinniah, Rathika; Ravi, Padma Malini; Mosses Joseph, Arun Kumar; Vellaiappan, Neethi Arasu; Krishnan, Jeyaram Illiayaraja; Karuppiah, Balakrishnan

    2014-01-01

    Two hundred ischemic stroke patients and 193 age and sex matched healthy controls were studied for the presence of Angiotensin Converting Enzyme Insertion/Deletion (ACE I/D) gene polymorphism. The PCR studies revealed that ACE ‘II’ (OR = 2.055; p = 0.004) genotype and ‘I’ (OR = 1.411; p = 0.018) alleles were significantly associated with IS patients. Gender specific analysis revealed a strong association of ‘II’ (OR = 2.044; p = 0.014) genotype and ‘I’ (OR = 1.531; p = 0.011) allele with male sex. Classification of patients based on TOAST criteria, revealed a significant association for ‘II’ genotype (OR = 1.713; p = 0.043) and ‘I’ (OR = 1.382; p = 0.039) allele in LVD patients only. When the data was stratified based on age and sex, a statistically significant association was observed for ACE ‘II’ genotype (OR = 2.288; p = 0.006) and ‘I’ allele (OR = 1.395; p = 0.054) in IS male patients of > 50 years of age. The ACE ‘D’ allele was found to be increased in controls (OR = 0.709; p = 0.018) than IS patients. Multivariate logistic regression analysis showed that smoking and diabetes were the most powerful independent risk factor in LVD type of stroke. Thus, we presented here an evidence for a strong association of ACE ‘II’ genotype and ‘I’ allele compounded by factors such as smoking and diabetes among south Indian IS patients. PMID:25606450

  11. Identification of Enzyme Genes Using Chemical Structure Alignments of Substrate-Product Pairs.

    PubMed

    Moriya, Yuki; Yamada, Takuji; Okuda, Shujiro; Nakagawa, Zenichi; Kotera, Masaaki; Tokimatsu, Toshiaki; Kanehisa, Minoru; Goto, Susumu

    2016-03-28

    Although there are several databases that contain data on many metabolites and reactions in biochemical pathways, there is still a big gap in the numbers between experimentally identified enzymes and metabolites. It is supposed that many catalytic enzyme genes are still unknown. Although there are previous studies that estimate the number of candidate enzyme genes, these studies required some additional information aside from the structures of metabolites such as gene expression and order in the genome. In this study, we developed a novel method to identify a candidate enzyme gene of a reaction using the chemical structures of the substrate-product pair (reactant pair). The proposed method is based on a search for similar reactant pairs in a reference database and offers ortholog groups that possibly mediate the given reaction. We applied the proposed method to two experimentally validated reactions. As a result, we confirmed that the histidine transaminase was correctly identified. Although our method could not directly identify the asparagine oxo-acid transaminase, we successfully found the paralog gene most similar to the correct enzyme gene. We also applied our method to infer candidate enzyme genes in the mesaconate pathway. The advantage of our method lies in the prediction of possible genes for orphan enzyme reactions where any associated gene sequences are not determined yet. We believe that this approach will facilitate experimental identification of genes for orphan enzymes.

  12. Lack of any association between insertion/deletion (I/D) polymorphisms in the angiotensin-converting enzyme gene and digestive system cancer risk: a meta-analysis.

    PubMed

    Liu, Jin-Fei; Xie, Hao-Jun; Cheng, Tian-Ming

    2013-01-01

    To investigate the association between the gene polymorphisms of angiotensin-converting enzyme (ACE) and digestive system cancer risk. A search was performed in Pubmed, Medline, ISI Web of Science and Chinese Biomedical (CBM) databases, covering all studies until Sep 1st, 2013. Statistical analysis was performed by using Revman5.2 and STATA 12.0. A total of 15 case-control studies comprising 2,390 digestive system cancer patients and 9,706 controls were identified. No significant association was found between the I/D polymorphism and digestive cancer risk (OR =0.93, 95%CI = (0.75, 1.16), P =0.53 for DD+DI vs. II). In the subgroup analysis by ethnicity and cancer type, no significant associations were found for the comparison of DD+DI vs. II. Results from other comparative genetic models also indicated a lack of associations between this polymorphism and digestive system cancer risks. This meta-analysis suggested that the ACE D/I polymorphism might not contribute to the risk of digestive system cancer.

  13. Gene Cloning, Expression and Enzyme Activity of Vitis vinifera Vacuolar Processing Enzymes (VvVPEs)

    PubMed Central

    Gong, Peijie; Li, Shuxiu; Wang, Yuejin; Zhang, Chaohong

    2016-01-01

    Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvβVPE, VvγVPE, and VvδVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the ‘Vitis vinifera cv. Pinot Noir’ and ‘Vitis vinifera cv. Thompson Seedless’ varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvγVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvδVPE is only expressed in flowers, buds and ovules, that VvγVPE is expressed in various tissues, and that VvβVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvβVPE in seeded grapes increased significantly at 30 days after full-bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvβVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs. PMID:27551866

  14. Gene Cloning, Expression and Enzyme Activity of Vitis vinifera Vacuolar Processing Enzymes (VvVPEs).

    PubMed

    Tang, Yujin; Wang, Ruipu; Gong, Peijie; Li, Shuxiu; Wang, Yuejin; Zhang, Chaohong

    2016-01-01

    Vacuolar processing enzymes (VPEs) have received considerable attention due to their caspase-1-like activity and ability to regulate programmed cell death (PCD), which plays an essential role in the development of stenospermocarpic seedless grapes ovules. To characterize VPEs and the relationship between stenospermocarpic grapes and the VPE gene family, we identified 3 Vitis vinifera VPE genes (VvβVPE, VvγVPE, and VvδVPE) from the PN40024 grape genome and cloned the full-length complementary DNAs (cDNAs) from the 'Vitis vinifera cv. Pinot Noir' and 'Vitis vinifera cv. Thompson Seedless' varietals. Each of the VPEs contained a typical catalytic dyad [His (177), Cys (219)] and substrate binding pocket [Arg (112), Arg (389), Ser (395)], except that Ser (395) in the VvγVPE protein sequence was replaced with alanine. Phylogenetic analysis of 4 Arabidopsis thaliana and 6 Vitis vinifera VPEs revealed that the 10 VPEs form 3 major branches. Furthermore, the 6 grapevine VPEs share a similar gene structure, with 9 exons and 8 introns. The 6 grapevine VPEs are located on 3 different chromosomes. We also tested the enzymatic activity of recombinant VPEs expressed in the Pichia Pastoris expression system and found that the VvVPEs exhibit cysteine peptidase activity. Tissue-specific expression analysis showed that VvδVPE is only expressed in flowers, buds and ovules, that VvγVPE is expressed in various tissues, and that VvβVPE was expressed in roots, flowers, buds and ovules. The results of quantitative real-time PCR (qRT-PCR) suggested that VvβVPE in seeded grapes increased significantly at 30 days after full-bloom (DAF), close to the timing of endosperm abortion at 32 DAF. These results suggested that VvβVPE is related to ovule abortion in seedless grapes. Our experiments provide a new perspective for understanding the mechanism of stenospermocarpic seedlessness and represent a useful reference for the further study of VPEs.

  15. Epitope mapping of mAbs to denatured human testicular ACE (CD143).

    PubMed

    Balyasnikova, I V; Metzger, R; Franke, F E; Conrad, N; Towbin, H; Schwartz, D E; Sturrock, E D; Danilov, S M

    2008-10-01

    Angiotensin I-converting enzyme (ACE; CD143) has two homologous enzymatically active domains (N and C) and plays a crucial role in blood pressure regulation and vascular remodeling. A wide spectrum of monoclonal antibodies (mAbs) to different epitopes on the N and C domains of human ACE have been used to study different aspects of ACE biology. In this study, we characterized a set of nine mAbs, developed against the C domain of human ACE, which recognize the denatured forms of ACE and thus are suitable for the detection and quantification of somatic ACE (sACE) and testicular ACE (tACE) using Western blotting and immunohistochemistry on paraffin-embedded human tissues. The epitopes for these mAbs were defined using species cross-reactivity, phage display library screening, Western blotting and ACE mutagenesis. Most of the mAbs recognized common/overlapping region(s) on both somatic and testicular forms of human ACE, whereas mAb 4E10 was relatively specific for the testicular isoform and mAb 5B9 mainly recognized the glycan attached to Asn 731. This set of mAbs is useful for identifying even subtle changes in human ACE conformation because of denaturation. These mAbs are also sensitive tools for the detection of human sACE and tACE in biological fluids and tissues using proteomic approaches. Their high reactivity in paraffin-embedded tissues provides opportunities to study changes in the pattern of ACE expression and glycosylation (particularly with mAb 5B9) in different tissues and cells.

  16. Biological activity of recombinant accessory cholerae enterotoxin (ace) on rabbit ileal loops and antibacterial assay.

    PubMed

    Anvari, Shaghayegh; Najar Peerayeh, Shahin; Behmanesh, Mehrdad; Boustanshenas, Mina

    2012-01-01

    Vibrio cholerae (V. cholerae) causes a potentially lethal disease named cholera. The cholera enterotoxin (CT) is a major virulence factor of V. cholerae. In addition to CT, V. cholerae produces other putative toxins, such as the zonula occludens toxin (Zot) and accessory cholera enterotoxin (Ace). The ace gene is the third gene of the V. cholerae virulence cassette. The Ace toxin alters ion transport, causes fluid accumulation in ligated rabbit ileal loops, and is a cause of mild diarrhea. The aim of this study is the cloning and overexpression of the ace gene into Escherichia coli (E. coli) and determination of some characteristics of the recombinant Ace protein. In this experimental study, the ace gene was amplified from V. cholerae strain 62013, then cloned in a pET28a expression vector and transformed into an E. coli (DH5 α) host strain. Subsequently, the recombinant vector was retransformed into E. coli BL21 for expression, induced by isopropythio-β-D-galctoside (IPTG) at a different concentration, and examined by SDS-PAGE and Western blot. A rabbit ileal loop experiment was conducted. Antibacterial activity of the Ace protein was assessed for E. coli, Stapylococcus aureus (S. aureus), and Pseudomonas aeruginosa (P. aeruginosa). The recombinant Ace protein with a molecular weight of 18 kDa (dimeric form) was expressed in E. coli BL21. The Ace protein showed poor staining with Coomassie blue stain, but stained efficiently with silver stain. Western blot analysis showed that the recombinant Ace protein reacted with rabbit anti-V. cholerae polyclonal antibody. The Ace protein had antibacterial activity at a concentration of ≥200 µg/ml and caused significant fluid accumulation in the ligated rabbit ileal loop test. This study described an E. coli cloning and expression system (E. coli BL21- pET-28a-ace) for the Ace protein of V. cholerae. We confirmed the antibacterial properties and enterotoxin activity of the resultant recombinant Ace protein.

  17. Structure of human ACE gives new insights into inhibitor binding and design.

    PubMed

    Brew, Keith

    2003-08-01

    Angiotensin-converting enzyme (ACE) is a primary target of drugs used for controlling hypertension. A new X-ray crystallographic structure of the key catalytic domain of ACE provides detailed information about the structure of its active site, located in a deep channel, and its interactions with an inhibitor. Such information might facilitate the rational design of ACE inhibitors that are more potent and more selective and therefore of clinical use.

  18. RETRACTED: Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population.

    PubMed

    Zhong, Weiqiang; Jiang, Zongpei; Zhou, Tian-Biao

    2015-12-01

    This article has been included in a multiple retraction: Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10.1177/1470320314566019 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January 26, 2015 doi: 10

  19. RETRACTED: Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population.

    PubMed

    Zhou, Tian-Biao; Guo, Xue-Feng; Jiang, Zongpei; Li, Hong-Yan

    2015-12-01

    The following article has been included in a multiple retraction: Tian-Biao Zhou, Xue-Feng Guo, Zongpei Jiang, and Hong-Yan Li Relationship between the ACE I/D gene polymorphism and T1DN susceptibility/risk of T1DM developing into T1DN in the Caucasian population Journal of Renin-Angiotensin-Aldosterone System 1470320314563425, first published on February 1, 2015 doi: 10.1177/1470320314563425 This article has been retracted at the request of the Editors and the Publisher. After conducting a thorough investigation, SAGE found that the submitting authors of a number of papers published in the Journal of the Renin-Angiotensin Aldosterone System ( JRAAS) (listed below) had supplied fabricated contact details for their nominated reviewers. The Editors accepted these papers based on the reports supplied by the individuals using these fake reviewer email accounts. After concluding that the peer review process was therefore seriously compromised, SAGE and the journal Editors have decided to retract all affected articles. Online First articles (these articles will not be published in an issue) Wenzhuang Tang, Tian-Biao Zhou, and Zongpei Jiang Association of the angiotensinogen M235T gene polymorphism with risk of diabetes mellitus developing into diabetic nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563426, first published on December 18, 2014 doi: 10.1177/1470320314563426 Tian-Biao Zhou, Hong-Yan Li, Zong-Pei Jiang, Jia-Fan Zhou, Miao-Fang Huang, and Zhi-Yang Zhou Role of renin-angiotensin-aldosterone system inhibitors in radiation nephropathy Journal of Renin-Angiotensin-Aldosterone System 1470320314563424, first published on December 18, 2014 doi: 10.1177/1470320314563424 Weiqiang Zhong, Zongpei Jiang, and Tian-Biao Zhou Association between the ACE I/D gene polymorphism and T2DN susceptibility: The risk of T2DM developing into T2DN in the Asian population Journal of Renin-Angiotensin-Aldosterone System 1470320314566019, first published on January

  20. Lack of Association Between ACE Indel Polymorphism and Cardiorespiratory Fitness in Physically Active and Sedentary Young Women

    PubMed Central

    Verlengia, Rozangela; Rebelo, Ana C.; Crisp, Alex H.; Kunz, Vandeni C.; dos Santos Carneiro Cordeiro, Marco A.; Hirata, Mario H.; Crespo Hirata, Rosario D.; Silva, Ester

    2014-01-01

    Background: Polymorphisms at the angiotensin-converting enzyme gene (ACE), such as the indel [rs1799752] variant in intron 16, have been shown to be associated with aerobic performance of athletes and non-athletes. However, the relationship between ACE indel polymorphism and cardiorespiratory fitness has not been always demonstrated. Objectives: The relationship between ACE indel polymorphism and cardiorespiratory fitness was investigated in a sample of young Caucasian Brazilian women. Patients and Methods: This study investigated 117 healthy women (aged 18 to 30 years) who were grouped as physically active (n = 59) or sedentary (n = 58). All subjects performed an incremental exercise test (ramp protocol) on a cycle-ergometer with 20-25 W/min increments. Blood samples were obtained for DNA extraction and to analyze metabolic and hormonal profiles. ACE indel polymorphism was determined by polymerase chain reaction (PCR) and fragment size analysis. Results: The physically active group had higher values of peak oxygen uptake (VO2 peak), carbon dioxide output (VCO2), ventilation (VE) and power output than the sedentary group (P < 0.05) at the peak of the exercise test. However, heart rate (HR), systolic blood pressure (SBP) and diastolic blood pressure (DBP) did not differ between groups. There was no relationship between ACE indel polymorphism and cardiorespiratory variables during the test in both the physically active and sedentary groups, even when the dominant (DD vs. D1 + 2) and recessive (2 vs. DI + DD) models of inheritance were tested. Conclusions: These results do not support the concept that the genetic variation at the ACE locus contributes to the cardiorespiratory responses at the peak of exercise test in physically active or sedentary healthy women. This indicates that other factors might mediate these responses, including the physical training level of the women. PMID:25520764

  1. The ACE2-angiotensin-(1-7)-Mas axis protects against pancreatic cell damage in cell culture.

    PubMed

    Wang, Jing; Liu, Ruixia; Qi, Haiyu; Wang, Yan; Cui, Lijian; Wen, Yan; Li, Huihui; Yin, Chenghong

    2015-03-01

    Angiotensin-converting enzyme 2 (ACE2), its product angiotensin-(1-7), and its receptor Mas have been shown to moderate the adverse effects of the ACE-angiotensin II-AT1 axis in many diseases. The aim of this study was to determine whether the ACE2-Ang-(1-7)-Mas axis could have similar effects in a cell culture model of pancreatic damage. AR42J cells were stimulated with 10 nmol/L cerulein to simulate acute pancreatitis. ACE2, Ang-(1-7), Mas receptor, and PI3K/AKT pathway were measured by quantitative real-time polymerase chain reaction and Western blot analysis. ACE2 and Mas receptor protein levels in AR42J cells were significantly increased (P < 0.05) between 30 minutes and 6 hours postdisease induction compared with the control group. Mas receptor gene expression was significantly increased (P < 0.05) at 2 hours postdisease induction, and Ang-(1-7) was increased at 6 hours. Treatment with Ang-(1-7) in AR42J cells increased IL-10, decreased IL-6 and IL-8, and reduced the damage to pancreatic cells. Levels of IL-6 and IL-8 in AR42J cell culture were increased significantly after treatment with A779. Moreover, Ang-(1-7) increased the concentration of PI3K/AKT pathway and eNOSin AR42J cells. ACE2-angiotensin-(1-7)-Mas axis significantly inhibits pancreatitis in response to decreased inflammatory factors by the activation of endothelial nitric oxide synthase and NO signaling pathways.

  2. Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.

    PubMed

    Klimas, Jan; Olvedy, Michael; Ochodnicka-Mackovicova, Katarina; Kruzliak, Peter; Cacanyiova, Sona; Kristek, Frantisek; Krenek, Peter; Ochodnicky, Peter

    2015-08-01

    Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs.

  3. γ-Aminobutyric Acid (GABA) Production and Angiotensin-I Converting Enzyme (ACE) Inhibitory Activity of Fermented Soybean Containing Sea Tangle by the Co-Culture of Lactobacillus brevis with Aspergillus oryzae.

    PubMed

    Jang, Eun Kyeong; Kim, Nam Yeun; Ahn, Hyung Jin; Ji, Geun Eog

    2015-08-01

    To enhance the γ-aminobutyric acid (GABA) content, the optimized fermentation of soybean with added sea tangle extract was evaluated at 30°C and pH 5.0. The medium was first inoculated with Aspergillus oryzae strain FMB S46471 and fermented for 3 days, followed by the subsequent inoculation with Lactobacillus brevis GABA 100. After fermentation for 7 days, the fermented soybean showed approximately 1.9 g/kg GABA and exhibited higher ACE inhibitory activity than the traditional soybean product. Furthermore, several peptides in the fraction containing the highest ACE inhibitory activity were identified. The novel fermented soybean enriched with GABA and ACE inhibitory components has great pharmaceutical and functional food values.

  4. Decrease of serum Angiotensin converting enzyme levels upon telbivudine treatment for chronic hepatitis B virus infection and negative correlations between the enzyme levels and estimated glumerular filtration rates.

    PubMed

    Liang, Kung-Hao; Chen, Yi-Cheng; Hsu, Chao-Wei; Chang, Ming-Ling; Yeh, Chau-Ting

    2014-01-01

    During antiviral therapy for chronic hepatitis B, renal function impairment could be a critical concern when oral nucleot(s)ide analogues were used. Paradoxically, long-term telbivudine treatment was associated with an increase of estimated glomerular filtration rate (eGFR) through unknown mechanisms. We aimed to investigate changes in serum protein abundances associated with renal function in response to antiviral treatments. Primarily, a transcriptomic assay was performed to identify differentially expressed genes in peripheral blood cells caused by the telbivudine treatment. Two genes coding angiotensin converting enzyme (ACE) and complement factor H (CFH) were screened from 14 candidate renal function-related genes. ACE and CFH production were further investigated using enzyme-linked immunoassays. Verification studies showed no significant change of serum CFH levels, but there was a significant reduction of serum ACE levels by continuous telbivudine treatment for 330.00 ± 0.85 days (34 patients; paired t-test, P = 0.022). Serum HBV DNA and ALT levels also decreased (P = 0.008 and < 0.001, respectively). A significant increase in eGFR was found (33 patients, paired t-test, P = 0.002) at 708.64 ± 31.63 days. Patients' eGFRs were negatively correlated with serum ACE levels (r = -0.375, P = 0.002) but not with serum HBV DNA and ALT levels (P = 0.241 and 0.088 respectively). Significant decreases of the ACE levels were also observed upon entecavir treatment (20 patients; paired t-test, P = 0.020) at 412.88 ± 36.92 days. No significant correlation was found between serum ACE levels and eGFRs (r = -0.239, P = 0.138) in entecavir-treated patients. We discovered a consistent reduction of serum ACE levels by two oral antiviral monotherapies, entecavir and telbivudine. Serum ACE levels were negatively correlated with eGFRs in telbivudine treated patients.

  5. [Effect of exogenic proteolytic enzymes on transfer of plasmid genes in mixed bacterial biofilms].

    PubMed

    Tets, G V; Artemenko, N K; Zaslavskaia, N V; Artemenko, K L; Knorring, G Iu; Tets, V V; Sternin, Iu I

    2009-01-01

    The effect of the enzyme complex from Vobenzin on transfer of plasmid genes in biofilms of gramnegative bacteria was studied. The extracellular matrix of the bacterial biofilms was shown to contain extracellular DNA carrying the antibiotic resistance markers. The action of the enzyme complex resulted in lower frequency of the antibiotic resistance genes transfer in mixed bacterial biofilms.

  6. Association between RAS gene polymorphisms (ACE I/D, AGT M235T) and Henoch-Schönlein purpura in a Turkish population.

    PubMed

    Nalbantoglu, Sinem; Tabel, Yılmaz; Mir, Sevgi; Serdaroğlu, Erkin; Berdeli, Afig

    2013-01-01

    Henoch-Schönlein purpura (HSP) is a small-vessel vasculitis of autoimmune hypersensitivity, and renin-angiotensin system (RAS) regulates vascular homeostasis and inflammation with activation of cytokine release. Thus, we aimed to investigate the association between HSP and ACE I/D and AGT M235T polymorphisms. Genotyping was determined by allele specific PCR and PCR-RFLP. We obtained a significant difference in genotype distribution (p=0.003) and allele frequencies (p<0.001) of ACE I/D polymorphism between patients and controls, while no significant association was detected in genotype distribution (p> 0.05) and allele frequencies (p> 0.05) of the AGT M235T polymorphism. Risk assessment showed significant risk for HSP in the subjects both with the ID + DD genotype (p=0.019, OR: 2.288, 95% CI: 1.136-4.609) and D allele (OR: D vs. I: 2.0528, 95% CI: 1.3632-3.0912, p=0.001) while no significant risk was obtained for HSP in the subjects both with the MT + TT genotype (p=0.312, OR: 1.3905, 95% T vs. M: 1.065, 95% CI: 0.7326-2.6391) and T allele (OR: patients were stratified by the presence of certain systemic complications of HSP, no significant association was detected with ACE I/D, and AGT M235T polymorphisms. Our findings suggest that ACE I/D polymorphism is significantly associated with HSP susceptibility.

  7. ACE I/D genotype-related increase in ACE plasma activity is a better predictor for schizophrenia diagnosis than the genotype alone.

    PubMed

    Gadelha, Ary; Yonamine, Camila M; Ota, Vanessa K; Oliveira, Vitor; Sato, João Ricardo; Belangero, Sintia I; Bressan, Rodrigo A; Hayashi, Mirian A F

    2015-05-01

    Angiotensin-I converting enzyme (ACE) is a key component of the renin-angiotensin system (RAS). Although the several contradictory data, ACE has been associated with schizophrenia (SCZ) pathophysiology. Here the ACE activity of SCZ patients and healthy controls (HCs), and its possible correlations with the ACE polymorphism genotype and symptomatic dimensions, was investigated. ACE activity of 86 SCZ patients and 100 HCs paired by age, gender and educational level was measured, using the FRET peptide substrate and the specific inhibitor lisinopril. The ACE insertion/deletion (I/D) genotypes were assessed by the restriction fragment length polymorphism (RFLP) technique. Significantly higher ACE activity was observed in SCZ patients compared to HCs (t=-5.09; p<0.001). The area under the receiver operating characteristic (ROC) curve was 0.701. Mean ACE activity levels were higher for the D-allele carriers (F=5.570; p=0.005), but no significant difference was found among SCZ patients and HCs for genotypes frequencies (Chi-squared=2.08; df=2; p=0.35). Interestingly, we found that the difference between the measured ACE activity for each SCZ patient and the expected average mean value for each respective genotype group (for control subjects) was a better predictor of SCZ than the ACE dichotomized values (high/low) or ACE I/D. Our results suggest that higher levels of ACE activity are associated with SCZ with stronger impact when the genetic background of each individual is considered. This may explain the heterogeneity of the results on ACE previously reported. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. ACEE composite structures technology

    NASA Technical Reports Server (NTRS)

    Klotzsche, M. (Compiler)

    1984-01-01

    The NASA Aircraft Energy Efficiency (ACEE) Composite Primary Aircraft Structures Program has made significant progress in the development of technology for advanced composites in commercial aircraft. Commercial airframe manufacturers have demonstrated technology readiness and cost effectiveness of advanced composites for secondary and medium primary components and have initiated a concerted program to develop the data base required for efficient application to safety-of-flight wing and fuselage structures. Oral presentations were compiled into five papers. Topics addressed include: damage tolerance and failsafe testing of composite vertical stabilizer; optimization of composite multi-row bolted joints; large wing joint demonstation components; and joints and cutouts in fuselage structure.

  9. Association of angiotensin-converting enzyme I gene I/D polymorphism with endometrial but not with ovarian cancer.

    PubMed

    Correa-Noronha, Silvana Aparecida Alves; Noronha, Samuel Marcos Ribeiro de; Alecrim, Cheryl; Mesquita, Adriana de Carvalho; Brito, Gabriela Soares da Silva; Junqueira, Michele Gilvana; Leite, Daniela Batista; Carvalho, Cristina Valletta de; Silva, Ismael Dale Cotrim Guerreiro da

    2012-11-01

    Associations have been found between the angiotensin-converting enzyme insertion deletion (I/D) polymorphism (ACE I/D) and endometrial and epithelial ovarian cancer (EC and EOC, respectively). In this study, the following frequencies for each of three ACE polymorphisms, DD, ID, and II, respectively, were observed: in the EC group, 55, 24, and 21% versus the control group 39, 40, and 21% (p = 0.033*); in the EOC group 49, 36, and 15% versus the control group 49, 33, and 18% (p = 0.82). According to these allelic distributions, DD carriers are 2.0 times more likely than individuals carrying the ID or II genotypes to develop EC; therefore, the DD genotype seems to be protective against EC. In contrast, no association was observed between ACE (I/D) polymorphism with EOC. The ACE (I/D) polymorphism might play a role in the pathogenesis of EC and it should be considered when identifying genetic markers for EC.

  10. Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism and Vesicoureteral Reflux in Children: A Meta-Analysis of 14 Case-Control Studies.

    PubMed

    Ai, Jin-Wei; Liu, Yu; Zeng, Xian-Tao; Lei, Qing; Zou, Li; Pei, Bin

    2015-12-01

    Vesicoureteral reflux (VUR) is a common and serious urinary disease in children. It usually causes renal scar, urinary tract infection, and chronic renal failure. Previous studies showed the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism might be associated with VUR; however, the conclusions were inconsistent. Therefore we used the meta-analytic approach to clarify the effect of ACE I/D polymorphism on VUR risk.We systematically searched the PubMed, CNKI, and EMBASE databases to identify all the potentially related studies published up to February 4, 2015. Two reviewers independently selected studies and extracted data. The strength of the association was assessed using odd ratio (OR) with its 95% confidence interval (CI) based on fixed or random effects model. The STATA 12.0 software was used for data analysis.A total of 14 case-control studies involving 1197 VUR patients and 1320 healthy controls met the eligibility criteria. Results of meta-analysis showed significant association between ACE I/D polymorphism and VUR risk (D vs. I: OR = 1.28, 95% CI = 1.06-1.54, P = 0.01; DD vs. II: OR = 1.44, 95% CI = 1.12-1.85, P = 0.01; DD vs. DI + II: OR = 1.49, 95% CI = 1.23-1.79, P < 0.01; DD + DI vs. II: OR = 1.20, 95% CI = 0.84-1.72, P = 0.31). Subgroup analyses revealed varied results. In Turkish people, results of all the genetic models other than DI vs. II showed statistical significance; in Caucasians, DD vs. DI + II showed statistical significance; and in Asians, DI versus II showed statistical significance.Our meta-analysis indicated that the ACE I/D polymorphism might be associated with increased risk of VUR in children. However, due to the limitations, we suggest conducting additional studies with larger sample size and adjustment for various risk factors, in the future for further clarification.

  11. Nine novel angiotensin I-converting enzyme (ACE) inhibitory peptides from cuttlefish (Sepia officinalis) muscle protein hydrolysates and antihypertensive effect of the potent active peptide in spontaneously hypertensive rats.

    PubMed

    Balti, Rafik; Bougatef, Ali; Sila, Assaâd; Guillochon, Didier; Dhulster, Pascal; Nedjar-Arroume, Naima

    2015-03-01

    This study aimed to identify novel ACE inhibitory peptides from the muscle of cuttlefish. Proteins were hydrolyzed and the hydrolysates were then subjected to various types of chromatography to isolate the active peptides. Nine ACE inhibitory peptides were isolated and their molecular masses and amino acid sequences were determined using ESI-MS and ESI-MS/MS, respectively. The structures of the most potent peptides were identified as Val-Glu-Leu-Tyr-Pro, Ala-Phe-Val-Gly-Tyr-Val-Leu-Pro and Glu-Lys-Ser-Tyr-Glu-Leu-Pro. The first peptide displayed the highest ACE inhibitory activity with an IC50 of 5.22μM. Lineweaver-Burk plots suggest that Val-Glu-Leu-Tyr-Pro acts as a non-competitive inhibitor against ACE. Furthermore, antihypertensive effects in spontaneously hypertensive rats (SHR) also revealed that oral administration of Val-Glu-Leu-Tyr-Pro can decrease systolic blood pressure significantly (p<0.01). These results suggest that the Val-Glu-Leu-Tyr-Pro would be a beneficial ingredient for nutraceuticals and pharmaceuticals acting against hypertension and its related diseases. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  12. FIRE_ACE_SHIP_SSFR

    Atmospheric Science Data Center

    2017-04-26

    FIRE_ACE_SHIP_SSFR Project Title:  FIRE III ACE Discipline:  ... Level:  L3 Platform:  SHEBA Ship Instrument:  Solar Spectral Flux Radiometer ... Info:  Surface Heat Budget of the Arctic Ocean (SHEBA) Ship SCAR-B Block:  SCAR-B Products ...

  13. FIRE_ACE_UTRECHT_TOWER

    Atmospheric Science Data Center

    2015-10-28

    FIRE_ACE_UTRECHT_TOWER Project Title:  FIRE II ACE Discipline:  ... L3 Platform:  SHEBA Ship Site; Meteorological tower Instrument:  Eppley precision pyrgeometers Meteorological tower Spatial Coverage:  Fairbanks, Alaska and the surrounding ...

  14. FIRE III ACE Data Sets

    Atmospheric Science Data Center

    2017-04-26

    ... in conjunction with the Surface Heat Budget of the Arctic Ocean (SHEBA) Experiment. The FIRE-ACE focused on all aspects of Arctic cloud ... Alaska with measurements extending well over the Arctic Ocean (ship and aircraft). Relevant Documents:  FIRE_ACE ...

  15. ACES's Challenges: Past Presidents Comment.

    ERIC Educational Resources Information Center

    Sheeley, Vernon Lee

    1990-01-01

    Recognizes the golden anniversary of the Association for Counselor Education and Supervision (ACES) and presents the statements of 15 past presidents of the association. Presidential leaders briefly review the association's past and suggest opportunities to help create a promising future for ACES. Outlines nine challenges which confront members of…

  16. Convergent evidences from human and animal studies implicate angiotensin I-converting enzyme activity in cognitive performance in schizophrenia

    PubMed Central

    Gadelha, A; Vendramini, A M; Yonamine, C M; Nering, M; Berberian, A; Suiama, M A; Oliveira, V; Lima-Landman, M T; Breen, G; Bressan, R A; Abílio, V; Hayashi, M A F

    2015-01-01

    In schizophrenia (SCZ), higher angiotensin I-converting enzyme (ACE) levels have been reported in patient's blood and cerebrospinal fluid (CSF). Hereby, we propose to explore whether the ACE activity levels are associated to cognitive performance in SCZ. Seventy-two patients with SCZ or schizoaffective disorder diagnosis, and 69 healthy controls (HCs) underwent a cognitive battery with parallel collection of peripheral blood samples to measure ACE activity. Significant higher ACE activity levels were confirmed in the plasma of SCZ patients compared with HCs (Student's t=−5.216; P<0.001). ACE activity significantly correlated to Hopkins delayed recall measures (r=−0.247; P=0.004) and Hopkins total (r=−0.214; P=0.012). Subjects grouped as high ACE activity (above average) had worse performance compared with low ACE activity level group for Hopkins delayed recall measure, even after correction for clinical condition, age, gender and years of education (P=0.029). The adjusted R squared for this final model was 0.343. This result was evident only comparing extreme groups for ACE activity, when splitting the sample in three groups with similar number of subjects. To clarify this finding, we performed an evaluation of the cognitive performance of transgenic mice with three copies of ACE gene in novel object recognition (NOR) test, which showed that such animals presented impairment in NOR (P<0.05) compared with two copies of wild-type animals. The results observed in SCZ patients and animal model suggest both the association of ACE to cognitive deficits in SCZ. This finding may support the evaluation of novel treatment protocols and/or of innovative drugs for specific intervention of cognitive deficits in SCZ envisioning concomitant ACE activity and behavior evaluations. PMID:26645626

  17. [Association and interaction of AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R and PTGS2 genes on the risk of hypertension in Antioquian population].

    PubMed

    Valencia, Diana María; Naranjo, Carlos Andrés; Parra, María Victoria; Caro, María Antonieta; Valencia, Ana Victoria; Jaramillo, Carlos José; Bedoya, Gabriel

    2013-01-01

    Hypertension is a multifactorial disease influenced by genetic and environmental components, with its prevalence varying across ethnic groups. Manifold studies on blood pressure regulatory system genes have been carried out -such as the renin-angiotensin-aldosterone system, the sympathetic nervous system, endothelial factor, and sodium balance-, but the results yielded were inconsistent among populations. To evaluate the effect of both variants in genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R PTGS2, and the result of the individual ancestry component on hypertension and blood pressure levels among population in Antioquia. 107 cases and 253 controls were genotyped for 12 variants on genes AGT, AGTR1, ACE, ADRB2, DRD1, ADD1, ADD2, ATP2B1, TBXA2R y PTGS2, and for 20 ancestry informative markers. The association of polymorphisms and their interactions, and the association of ancestral genetic composition with hypertension and blood pressure levels were examined. Genes ADD2, rs4852706 (OR=3.0; p=0.023); DRD1, rs686 (OR=0.38; p=0.012) and ADRB2, rs1042718 (OR=10.0; p=0.008); as well as genotypic combinations of DRD1 and AGTR1; AGT and ADD1; and ADD1 to ATP2B1 and PTGS2 were associated to hypertension. The Amerindian ancestry component was associated to some decrease in diastolic blood pressure. Variants on genes ADD2, DRD1, ADRB2, AGTR1, AGT, ADD1, ATP2B1 and PTGS2 individually or interacting, are associated to hypertension. The Amerindian ancestry component has an effect on blood pressure.

  18. Relationship between ace genotype and short duration aerobic performance development.

    PubMed

    Cerit, Mesut; Colakoglu, Muzaffer; Erdogan, Murat; Berdeli, Afig; Cam, Fethi Sirri

    2006-11-01

    We have previously demonstrated that, ACE D allele may be related with a better performance in short duration aerobic endurance in a homogeneous cohort with similar training backgrounds. We aimed to study the variation in the short-duration aerobic performance development amongst ACE genotypes in response to identical training programs in homogeneous populations. The study group consisted of 186 male Caucasian non-elite Turkish army recruits. All subjects had undergone an identical training program with double training session per day and 6 days a week for 6 months. Performances for middle distance runs (2,400 m) were evaluated on an athletics track before and after the training period. ACE gene polymorphisms were studied by PCR analysis. The distribution of genotypes in the whole group was 16.7% II, n=31; 46.2% ID, n=86; 37.1% DD, n=69. Subjects with ACE DD genotype had significantly higher enhancement than the ID (P<0.01) and II (P<0.05) genotype groups. Around 2,400 m performance enhancement ratios showed a linear trend as ACE DD>ACE ID>ACE II (P value for Pearson chi2=0.461 and P value for linear by linear association=0.001). ACE DD genotype seems to have an advantage in development in short-duration aerobic performance. This data in unison with the data that we have obtained from homogenous cohorts previously is considered as an existence of threshold for initiation of ACE I allele effectiveness in endurance performance. This threshold may be anywhere between 10 and 30 min with lasting maximal exercises.

  19. The transferome of metabolic genes explored: analysis of the horizontal transfer of enzyme encoding genes in unicellular eukaryotes.

    PubMed

    Whitaker, John W; McConkey, Glenn A; Westhead, David R

    2009-01-01

    Metabolic networks are responsible for many essential cellular processes, and exhibit a high level of evolutionary conservation from bacteria to eukaryotes. If genes encoding metabolic enzymes are horizontally transferred and are advantageous, they are likely to become fixed. Horizontal gene transfer (HGT) has played a key role in prokaryotic evolution and its importance in eukaryotes is increasingly evident. High levels of endosymbiotic gene transfer (EGT) accompanied the establishment of plastids and mitochondria, and more recent events have allowed further acquisition of bacterial genes. Here, we present the first comprehensive multi-species analysis of E/HGT of genes encoding metabolic enzymes from bacteria to unicellular eukaryotes. The phylogenetic trees of 2,257 metabolic enzymes were used to make E/HGT assertions in ten groups of unicellular eukaryotes, revealing the sources and metabolic processes of the transferred genes. Analyses revealed a preference for enzymes encoded by genes gained through horizontal and endosymbiotic transfers to be connected in the metabolic network. Enrichment in particular functional classes was particularly revealing: alongside plastid related processes and carbohydrate metabolism, this highlighted a number of pathways in eukaryotic parasites that are rich in enzymes encoded by transferred genes, and potentially key to pathogenicity. The plant parasites Phytophthora were discovered to have a potential pathway for lipopolysaccharide biosynthesis of E/HGT origin not seen before in eukaryotes outside the Plantae. The number of enzymes encoded by genes gained through E/HGT has been established, providing insight into functional gain during the evolution of unicellular eukaryotes. In eukaryotic parasites, genes encoding enzymes that have been gained through horizontal transfer may be attractive drug targets if they are part of processes not present in the host, or are significantly diverged from equivalent host enzymes.

  20. Molecular characterization of genes encoding trypsin-like enzymes from Aedes aegypti larvae and identification of digestive enzymes.

    PubMed

    Soares, Tatiane S; Watanabe, Renata M O; Lemos, Francisco J A; Tanaka, Aparecida S

    2011-12-10

    Trypsin-like enzymes play an important role in the Aedes aegypti digestive process. The trypsin-like enzymes present in adults were characterized previously, but little is known about trypsins in larvae. In the present work, we identified one of the trypsin enzymes from Ae. aegypti larval midgut using a library of trypsin gene fragments, which was the sequence known as AAEL005607 from the Ae. aegypti genome. Quantitative PCR analysis showed that AAEL005607 was transcribed in all larval instars, but it was not present in adult midgut. In order to confirm transcription data, the trypsin-like enzymes from 4th instar larvae of Ae. aegypti midgut were purified and sequenced. Purified trypsin showed identity with the amino-terminal sequence of AAEL005607, AAEL005609 and AAEL005614. These three trypsins have high amino acids identity, and could all be used as a template for the design of inhibitors. In conclusion, for the first time, digestive enzymes of 4th larval instar of Ae. aegypti were purified and characterized. The knowledge of digestive enzymes present in Ae. aegypti larvae may be helpful in the development of a larvicide. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

    PubMed Central

    2011-01-01

    Background Metabolic Syndrome (MetS) results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala and Angiotensin Converting Enzyme (ACE) I/D polymorphisms with MetS and interaction between these genetic variants. Methods Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI) were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. Results The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002) and Fat Mass (p = 0.002). Pro12Ala was independently associated with waist circumference independent of BMI and gender. Conclusions Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution. PMID:22168210

  2. PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome.

    PubMed

    Passaro, Angela; Dalla Nora, Edoardo; Marcello, Caterina; Di Vece, Francesca; Morieri, Mario Luca; Sanz, Juana M; Bosi, Cristina; Fellin, Renato; Zuliani, Giovanni

    2011-12-14

    Metabolic Syndrome (MetS) results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala and Angiotensin Converting Enzyme (ACE) I/D polymorphisms with MetS and interaction between these genetic variants. Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI) were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping. The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002) and Fat Mass (p = 0.002). Pro12Ala was independently associated with waist circumference independent of BMI and gender. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.

  3. Selective restoration of male fertility in mice lacking angiotensin-converting enzymes by sperm-specific expression of the testicular isozyme.

    PubMed Central

    Ramaraj, P; Kessler, S P; Colmenares, C; Sen, G C

    1998-01-01

    Although angiotensin-converting enzyme (ACE) has been studied primarily in the context of its role in blood pressure regulation, this widely distributed enzyme has many other physiological functions. The ACE gene encodes two isozymes. The somatic isozyme is expressed in many tissues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells, whereas the testicular or germinal angiotensin-converting enzyme is expressed only in sperm. The ACE gene knockout mice lack both isozymes and they exhibit low blood pressure, kidney dysfunctions, and male infertility. Here, we report the use of a sperm-specific promoter and interbreeding of transgenic and gene knockout mice for generating a mouse strain that expressed ACE only in sperm. The experimental mice maintained the kidney defects of ACE-/- mice, but unlike the knockout strain, the males were fertile. Thus, we established that the role of ACE in male fertility is completely dependent on its exclusive expression in sperm. Our study clearly demonstrated how transgenic and knockout techniques can be combined for ascribing a specific physiological function to the expression of a multifunctional protein in a given tissue. PMID:9664078

  4. Correlation Index-Based Responsible-Enzyme Gene Screening (CIRES), a Novel DNA Microarray-Based Method for Enzyme Gene Involved in Glycan Biosynthesis

    PubMed Central

    Yamamoto, Harumi; Takematsu, Hiromu; Fujinawa, Reiko; Naito, Yuko; Okuno, Yasushi; Tsujimoto, Gozoh; Suzuki, Akemi; Kozutsumi, Yasunori

    2007-01-01

    Background Glycan biosynthesis occurs though a multi-step process that requires a variety of enzymes ranging from glycosyltransferases to those involved in cytosolic sugar metabolism. In many cases, glycan biosynthesis follows a glycan-specific, linear pathway. As glycosyltransferases are generally regulated at the level of transcription, assessing the overall transcriptional profile for glycan biosynthesis genes seems warranted. However, a systematic approach for assessing the correlation between glycan expression and glycan-related gene expression has not been reported previously. Methodology To facilitate genetic analysis of glycan biosynthesis, we sought to correlate the expression of genes involved in cell-surface glycan formation with the expression of the glycans, as detected by glycan-recognizing probes. We performed cross-sample comparisons of gene expression profiles using a newly developed, glycan-focused cDNA microarray. Cell-surface glycan expression profiles were obtained using flow cytometry of cells stained with plant lectins. Pearson's correlation coefficients were calculated for these profiles and were used to identify enzyme genes correlated with glycan biosynthesis. Conclusions This method, designated correlation index-based responsible-enzyme gene screening (CIRES), successfully identified genes already known to be involved in the biosynthesis of certain glycans. Our evaluation of CIRES indicates that it is useful for identifying genes involved in the biosynthesis of glycan chains that can be probed with lectins using flow cytometry. PMID:18043739

  5. The ACE2/Ang-(1-7)/Mas axis can inhibit hepatic insulin resistance.

    PubMed

    Cao, Xi; Yang, Fang-Yuan; Xin, Zhong; Xie, Rong-Rong; Yang, Jin-Kui

    2014-08-05

    Blocking the renin-angiotensin system (RAS) can reduce the risk of diabetes. Meanwhile, the angiotensin (Ang)-converting enzyme-2 (ACE2)/Ang-(1-7)/Mas axis has recently been proposed to function as a negative regulator of the RAS. In previous studies, we first demonstrated that ACE2 knockout (ACE2(-/)(y)) mice exhibit impaired glucose tolerance or diabetes. However the precise roles of ACE2 on glucose metabolism are unknown. Here we show that the ACE2/Ang-(1-7)/Mas axis can ameliorate insulin resistance in the liver. Activation of the ACE2/Ang-(1-7)/Mas axis increases glucose uptake and decreases glycogen synthesis in the liver accompanied by increased expression of glucose transporters, insulin receptor substrates and decreased expression of enzymes for glycogen synthesis. ACE2 knockout mice displayed elevated levels of oxidative stress and exposure to Ang-(1-7) reduced the stress in hepatic cells. As a consequence of anti-oxidative stress, activation of the ACE2/Ang-(1-7)/Mas axis led to improved hepatic insulin resistance through the Akt/PI3K/IRS-1/JNK insulin signaling pathway. This is the first time documented that the ACE2/Ang-(1-7)/Mas axis can ameliorate insulin resistance in the liver. As insulin resistance in the liver is considered to be the primary cause of the development of type 2 diabetes, this axis may serve as a new diabetes target. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  6. ACE overexpression in myelomonocytic cells: effect on a mouse model of Alzheimer's disease.

    PubMed

    Koronyo-Hamaoui, Maya; Shah, Kandarp; Koronyo, Yosef; Bernstein, Ellen; Giani, Jorge F; Janjulia, Tea; Black, Keith L; Shi, Peng D; Gonzalez-Villalobos, Romer A; Fuchs, Sebastien; Shen, Xiao Z; Bernstein, Kenneth E

    2014-07-01

    While it is well known that angiotensin converting enzyme (ACE) plays an important role in blood pressure control, ACE also has effects on renal function, hematopoiesis, reproduction, and aspects of the immune response. ACE 10/10 mice overexpress ACE in myelomonocytic cells. Macrophages from these mice have an increased polarization towards a pro-inflammatory phenotype that results in a very effective immune response to challenge by tumors or bacterial infection. In a mouse model of Alzheimer's disease (AD), the ACE 10/10 phenotype provides significant protection against AD pathology, including reduced inflammation, reduced burden of the neurotoxic amyloid-β protein and preserved cognitive function. Taken together, these studies show that increased myelomonocytic ACE expression in mice alters the immune response to better defend against many different types of pathologic insult, including the cognitive decline observed in an animal model of AD.

  7. The influence of angiotensin converting enzyme and bradykinin receptor B2 gene variants on voluntary fluid intake and fluid balance in healthy men during moderate-intensity exercise in the heat.

    PubMed

    Yau, Adora M W; Moss, Andrew D; James, Lewis John; Gilmore, William; Ashworth, Jason J; Evans, Gethin H

    2015-02-01

    Angiotensin converting enzyme (ACE) and bradykinin receptor B2 (B2R) genetic variation may affect thirst because of effects on angiotensin II production and bradykinin activity, respectively. To examine this, 45 healthy Caucasian men completed 60 min of cycle exercise at 62% ± 5% peak oxygen uptake in a room heated to 30.5 ± 0.3 °C with ad libitum fluid intake. Blood samples were collected pre-, mid-, and immediately post-cycle. Fluid intake, body mass loss (BML), sweat loss (determined via changes in body mass and fluid intake), and thirst sensation were recorded. All participants were genotyped for the ACE insert fragment (I) and the B2R insert sequence (P). Participants were homozygous for the wild-type allele (WW or MM), heterozygous (WI or MP) or homozygous for the insert (II or PP). No differences between genotype groups were found in mean (±SD) voluntary fluid intake (WW: 613 ± 388, WI: 753 ± 385, II: 862 ± 421 mL, p = 0.31; MM: 599 ± 322, MP: 745 ± 374, PP: 870 ± 459 mL, p = 0.20), percentage BML or any other fluid balance variables for both the ACE and B2R genes, respectively. Mean thirst perception in the B2R PP group, however, was higher (p < 0.05) than both MM and MP at 30, 45, and 60 min. In conclusion, the results of this study suggest that voluntary fluid intake and fluid balance in healthy men performing 60 min of moderate-intensity exercise in the heat are not predominantly influenced by ACE or B2R genetic variation.

  8. Role of homocysteinylation of ACE in endothelial dysfunction of arteries

    PubMed Central

    Huang, An; Pinto, John T.; Froogh, Ghezal; Kandhi, Sharath; Qin, Jun; Wolin, Michael S.; Hintze, Thomas H.

    2014-01-01

    The direct impact of de novo synthesis of homocysteine (Hcy) and its reactive metabolites, Hcy-S-S-Hcy and Hcy thiolactone (HCTL), on vascular function has not been fully elucidated. We hypothesized that Hcy synthesized within endothelial cells affects activity of angiotensin-converting enzyme (ACE) by direct homocysteinylation of its amino- and/or sulfhydryl moieties. This covalent modification enhances ACE reactivity toward angiotensin II (ANG II)-NADPH oxidase-superoxide-dependent endothelial dysfunction. Mesenteric and coronary arteries isolated from normal rats were incubated for 3 days with or without exogenous methionine (Met, 0.1–0.3 mM), a precursor to Hcy. Incubation of arteries in Met-free media resulted in time-dependent decreases in vascular Hcy formation. By contrast, vessels incubated with Met produced Hcy in a dose-dependent manner. There was a notably greater de novo synthesis of Hcy from endothelial than from smooth muscle cells. Enhanced levels of Hcy production significantly impaired shear stress-induced dilation and release of nitric oxide, events that are associated with elevated production of vascular superoxide. Each of these processes was attenuated by ANG II type I receptor blocker or ACE and NADPH oxidase inhibitors. In addition, in vitro exposure of purified ACE to Hcy-S-S-Hcy/HCTL resulted in formation of homocysteinylated ACE and an enhanced ACE activity. The enhanced ACE activity was confirmed in isolated coronary and mesenteric arteries that had been exposed directly to Hcy-S-S-Hcy/HCTL or after Met incubation. In conclusion, vasculature-derived Hcy initiates endothelial dysfunction that, in part, may be mediated by ANG II-dependent activation of NADPH oxidase in association with homocysteinylation of ACE. PMID:25416191

  9. Genome-Wide Prediction of Metabolic Enzymes, Pathways, and Gene Clusters in Plants1[OPEN

    PubMed Central

    Zhang, Peifen; Kim, Taehyong; Banf, Michael; Chavali, Arvind K.; Nilo-Poyanco, Ricardo; Bernard, Thomas

    2017-01-01

    Plant metabolism underpins many traits of ecological and agronomic importance. Plants produce numerous compounds to cope with their environments but the biosynthetic pathways for most of these compounds have not yet been elucidated. To engineer and improve metabolic traits, we need comprehensive and accurate knowledge of the organization and regulation of plant metabolism at the genome scale. Here, we present a computational pipeline to identify metabolic enzymes, pathways, and gene clusters from a sequenced genome. Using this pipeline, we generated metabolic pathway databases for 22 species and identified metabolic gene clusters from 18 species. This unified resource can be used to conduct a wide array of comparative studies of plant metabolism. Using the resource, we discovered a widespread occurrence of metabolic gene clusters in plants: 11,969 clusters from 18 species. The prevalence of metabolic gene clusters offers an intriguing possibility of an untapped source for uncovering new metabolite biosynthesis pathways. For example, more than 1,700 clusters contain enzymes that could generate a specialized metabolite scaffold (signature enzymes) and enzymes that modify the scaffold (tailoring enzymes). In four species with sufficient gene expression data, we identified 43 highly coexpressed clusters that contain signature and tailoring enzymes, of which eight were characterized previously to be functional pathways. Finally, we identified patterns of genome organization that implicate local gene duplication and, to a lesser extent, single gene transposition as having played roles in the evolution of plant metabolic gene clusters. PMID:28228535

  10. [Identification of genes encoding ligninolytic enzymes in naturally occurring basidiomycete isolates].

    PubMed

    Shevchenko, E A; Bessolitsyna, E A; Darmov, I V

    2013-01-01

    The presence of genes encoding lignin peroxidase, laccase, and manganese peroxidase was assessed in more than 20 types of polypore fungi collected in the woods of Kirov oblast; the fungi studied had not been previously characterized with regard to ligninolytic enzyme production. Fifteen isolates of eleven basidiomycete species were shown to contain genes coding for all three ligninolytic enzymes. Genes coding for these enzymes were detected in D. mollis, D. quercina, F. pinicola, G. trabeum, G. lucidum, H. fasciculare, L. betulina, P. betulinus, P. igniarus, P. pomaceus, P. pini, and P. cinnabarinus for the first time.

  11. Assembly and multiple gene expression of thermophilic enzymes in Escherichia coli for in vitro metabolic engineering.

    PubMed

    Ninh, Pham Huynh; Honda, Kohsuke; Sakai, Takaaki; Okano, Kenji; Ohtake, Hisao

    2015-01-01

    In vitro reconstitution of an artificial metabolic pathway is an emerging approach for the biocatalytic production of industrial chemicals. However, several enzymes have to be separately prepared (and purified) for the construction of an in vitro metabolic pathway, thereby limiting the practical applicability of this approach. In this study, genes encoding the nine thermophilic enzymes involved in a non-ATP-forming chimeric glycolytic pathway were assembled in an artificial operon and co-expressed in a single recombinant Escherichia coli strain. Gene expression levels of the thermophilic enzymes were controlled by their sequential order in the artificial operon. The specific activities of the recombinant enzymes in the cell-free extract of the multiple-gene-expression E. coli were 5.0-1,370 times higher than those in an enzyme cocktail prepared from a mixture of single-gene-expression strains, in each of which a single one of the nine thermophilic enzymes was overproduced. Heat treatment of a crude extract of the multiple-gene-expression cells led to the denaturation of indigenous proteins and one-step preparation of an in vitro synthetic pathway comprising only a limited number of thermotolerant enzymes. Coupling this in vitro pathway with other thermophilic enzymes including the H2 O-forming NADH oxidase or the malate/lactate dehydrogenase facilitated one-pot conversion of glucose to pyruvate or lactate, respectively.

  12. The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism.

    PubMed

    Vaughan, David; Brogioli, Michael; Maier, Thomas; White, Andy; Waldron, Sarah; Rittweger, Jörn; Toigo, Marco; Wettstein, Jessica; Laczko, Endre; Flück, Martin

    2016-01-01

    A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and -3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. The observations imply a genetically modulated role for ACE in control of glucose import and oxidation in working

  13. The Angiotensin Converting Enzyme Insertion/Deletion Polymorphism Modifies Exercise-Induced Muscle Metabolism

    PubMed Central

    Vaughan, David; Brogioli, Michael; Maier, Thomas; White, Andy; Waldron, Sarah; Rittweger, Jörn; Toigo, Marco; Wettstein, Jessica; Laczko, Endre; Flück, Martin

    2016-01-01

    Objective A silencer region (I-allele) within intron 16 of the gene for the regulator of vascular perfusion, angiotensin-converting enzyme (ACE), is implicated in phenotypic variation of aerobic fitness and the development of type II diabetes. We hypothesised that the reportedly lower aerobic performance in non-carriers compared to carriers of the ACE I-allele, i.e. ACE-DD vs. ACE-ID/ACE-II genotype, is associated with alterations in activity-induced glucose metabolism and capillarisation in exercise muscle. Methods Fifty-three, not-specifically trained Caucasian men carried out a one-legged bout of cycling exercise to exhaustion and/or participated in a marathon, the aim being to identify and validate genotype effects on exercise metabolism. Respiratory exchange ratio (RER), serum glucose and lipid concentration, glycogen, and metabolite content in vastus lateralis muscle based on ultra-performance lipid chromatography-mass spectrometry (UPLC-MS), were assessed before and after the cycling exercise in thirty-three participants. Serum metabolites were measured in forty subjects that completed the marathon. Genotype effects were assessed post-hoc. Results Cycling exercise reduced muscle glycogen concentration and this tended to be affected by the ACE I-allele (p = 0.09). The ACE-DD genotype showed a lower maximal RER and a selective increase in serum glucose concentration after exercise compared to ACE-ID and ACE-II genotypes (+24% vs. +2% and –3%, respectively). Major metabolites of mitochondrial metabolism (i.e. phosphoenol pyruvate, nicotinamide adenine dinucleotide phosphate, L-Aspartic acid, glutathione) were selectively affected in vastus lateralis muscle by exercise in the ACE-DD genotype. Capillary-to-fibre ratio was 24%-lower in the ACE-DD genotype. Individuals with the ACE-DD genotype demonstrated an abnormal increase in serum glucose to 7.7 mM after the marathon. Conclusion The observations imply a genetically modulated role for ACE in control of

  14. VO2 max is associated with ACE genotype in postmenopausal women.

    PubMed

    Hagberg, J M; Ferrell, R E; McCole, S D; Wilund, K R; Moore, G E

    1998-11-01

    Relationships have frequently been found between angiotensin-converting enzyme (ACE) genotype and various pathological and physiological cardiovascular outcomes and functions. Thus we sought to determine whether ACE genotype affected maximal O2 consumption (VO2 max) and maximal exercise hemodynamics in postmenopausal women with different habitual physical activity levels. Age, body composition, and habitual physical activity levels did not differ among ACE genotype groups. However, ACE insertion/insertion (II) genotype carriers had a 6.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE deletion/deletion (DD) genotype group after accounting for the effect of physical activity levels. The ACE II genotype group also had a 3.3 ml . kg-1 . min-1 higher VO2 max (P < 0.05) than the ACE insertion/deletion (ID) genotype group. The ACE ID group tended to have a higher VO2 max than the DD genotype group, but the difference was not significant. ACE genotype accounted for 12% of the variation in VO2 max among women after accounting for the effect of habitual physical activity levels. The entire difference in VO2 max among ACE genotype groups was the result of differences in maximal arteriovenous O2 difference (a-vDO2). ACE genotype accounted for 17% of the variation in maximal a-vDO2 in these women. Maximal cardiac output index did not differ whatsoever among ACE genotype groups. Thus it appears that ACE genotype accounts for a significant portion of the interindividual differences in VO2 max among these women. However, this difference is the result of genotype-dependent differences in maximal a-vDO2 and not of maximal stroke volume and maximal cardiac output.

  15. Cloning of fish enzymes and other fish protein genes.

    PubMed

    Macouzet, M; Simpson, B K; Lee, B H

    1999-01-01

    Fish metabolism needs special enzymes that have maximum activity at very different conditions than their mammalian counterparts. Due to the differences in activity, these enzymes, especially cold-adapted proteases, could be used advantageously for the production of some foods. In addition to the enzymes, this review describes some other unique fish polypeptides such as antifreeze proteins, fluorescent proteins, antitumor peptides, antibiotics, and hormones, that have already been cloned and used in food processing, genetic engineering, medicine, and aquaculture. Recombinant DNA technology, which allows these biological molecules to be cloned and overexpressed in microorganisms is also described, highlighting innovative applications. The expected impact of cloning fish proteins in different fields of technology is discussed.

  16. Neofunctionalization of a duplicate hatching enzyme gene during the evolution of teleost fishes.

    PubMed

    Sano, Kaori; Kawaguchi, Mari; Watanabe, Satoshi; Yasumasu, Shigeki

    2014-10-19

    Duplication and subsequent neofunctionalization of the teleostean hatching enzyme gene occurred in the common ancestor of Euteleostei and Otocephala, producing two genes belonging to different phylogenetic clades (clade I and II). In euteleosts, the clade I enzyme inherited the activity of the ancestral enzyme of swelling the egg envelope by cleavage of the N-terminal region of egg envelope proteins. The clade II enzyme gained two specific cleavage sites, N-ZPd and mid-ZPd but lost the ancestral activity. Thus, euteleostean clade II enzymes assumed a new function; solubilization of the egg envelope by the cooperative action with clade I enzyme. However, in Otocephala, the clade II gene was lost during evolution. Consequently, in a late group of Otocephala, only the clade I enzyme is present to swell the egg envelope. We evaluated the egg envelope digestion properties of clade I and II enzymes in Gonorynchiformes, an early diverging group of Otocephala, using milkfish, and compared their digestion with those of other fishes. Finally, we propose a hypothesis of the neofunctionalization process. The milkfish clade II enzyme cleaved N-ZPd but not mid-ZPd, and did not cause solubilization of the egg envelope. We conclude that neofunctionalization is incomplete in the otocephalan clade II enzymes. Comparison of clade I and clade II enzyme characteristics implies that the specificity of the clade II enzymes gradually changed during evolution after the duplication event, and that a change in substrate was required for the addition of the mid-ZPd site and loss of activity at the N-terminal region. We infer the process of neofunctionalization of the clade II enzyme after duplication of the gene. The ancestral clade II gene gained N-ZPd cleavage activity in the common ancestral lineage of the Euteleostei and Otocephala. Subsequently, acquisition of cleavage activity at the mid-ZPd site and loss of cleavage activity in the N-terminal region occurred during the evolution of

  17. Angiotensin converting enzyme from sheep mammary, lingual and other tissues.

    PubMed

    Rao, N Mallikarjuna; Udupa, E G Padmanabha

    2007-11-01

    Occurrence of angiotensin converting enzyme (ACE) in mammary gland and tongue taste epithelium was demonstrated for the first time. Six times higher ACE activity in lactating mammary gland, than non-lactating mammary gland, suggested pregnancy and lactation hormonal dependent expression of ACE in female mammals. ACE activity was highest in choroid plexus, less in spinal cord and moderate in cerebrum, medulla, cerebellum and pons. Distribution of ACE in different regions of skin, kidney and among other tissues was different. Presence of ACE in adrenal glands, pancreas, bone marrow and thyroid gland indicated functions other than blood pressure homeostasis for this enzyme.

  18. Metagenomic gene discovery and enzyme engineering for biomass conversion

    USDA-ARS?s Scientific Manuscript database

    Enzymes that can be harnessed for high-efficiency breakdown of agricultural crops and crop residues have become increasingly important because of their pivotal role in the conversion of these renewable biomass materials to biofuel and other high-value products. Microbial deconstruction of plant cel...

  19. Genetic Variation in ACE-related pathways associated with Sudden Cardiac Arrest Risk

    PubMed Central

    Sotoodehnia, Nona; Li, Guo; Johnson, Catherine O.; Lemaitre, Rozenn N.; Rice, Kenneth M.; Rea, Thomas D.; Siscovick, David S.

    2009-01-01

    Background Angiotensin converting enzyme (ACE)-related pathways influence arrhythmias and sudden cardiac arrest (SCA) risk. Objective We investigated whether genetic variation in ACE-related pathways are associated with SCA risk. Because these pathways are sex-dependent and influenced by estrogen, we examined these genotype-SCA associations in the full study population, and tested for interaction with gender. Methods In a population-based case-control study set in King County WA, we genotyped 211 SCA cases (mean age 59, 80% male) and 730 age- and gender-matched controls of European descent for 47 single nucleotide polymorphisms (SNPs) in eight genes (ACE, AGT, REN, AGTR1, AGTR2, ACE2, KNG1, BDKRB2). We examined association of SNPs and haplotypes with SCA risk using logistic regression. Results AGTR1 SNP rs1492099 (allele frequency=15%) was associated with decreased SCA risk (OR=0.62, 95%CI=0.4–0.9). Haplotype variation in AGTR2 was associated with SCA risk (global haplotype test p=0.001), with haplotype 2 (allele frequency=27%) associated with increased risk (OR=1.26, 95%CI=1.1–1.5). There was interaction with gender on SCA risk for variation in KNG1 (interaction p-value range=0.0004–0.017 for 6/8 SNPs). KNG1 SNP rs710448 (allele frequency=42%) was associated with decreased risk (OR=0.44, 95%CI=0.3–0.8) among women but not men. Other SNPs and haplotypes in the eight genes examined were not associated with SCA risk after multiple testing correction. Conclusions Variation in AGTR1 and AGTR2 are associated with SCA risk in a population-based case-control study. There was evidence of interaction with gender on SCA risk for variation in KNG1. Our findings, if replicated, suggest that variation in genes in ACE-related pathways influence SCA risk. PMID:19716087

  20. ACE3 Draft Indicators: Biomonitoring

    EPA Pesticide Factsheets

    The page information was provided by EPA in conjunction with the opportunity for public comment on the draft indicators for ACE3, which ran from March 8 – April 21, 2011. The public comment period is now closed.

  1. Wiseman in with ACE sample

    NASA Image and Video Library

    2014-05-30

    ISS040-E-006569 (2 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs an Advanced Colloids Experiment (ACE) sample 40-minute mixing activity in the Destiny laboratory of the International Space Station.

  2. Wiseman in with ACE sample

    NASA Image and Video Library

    2014-05-30

    ISS040-E-006567 (2 June 2014) --- NASA astronaut Reid Wiseman, Expedition 40 flight engineer, performs an Advanced Colloids Experiment (ACE) sample 40-minute mixing activity in the Destiny laboratory of the International Space Station.

  3. ACE3 Draft Indicators: Health

    EPA Pesticide Factsheets

    The page information was provided by EPA in conjunction with the opportunity for public comment on the draft indicators for ACE3, which ran from March 8 – April 21, 2011. The public comment period is now closed.

  4. [ACE inhibitors and the kidney].

    PubMed

    Hörl, W H

    1996-01-01

    Treatment with ACE inhibitors results in kidney protection due to reduction of systemic blood pressure, intraglomerular pressure, an antiproliferative effect, reduction of proteinuria and a lipid-lowering effect in proteinuric patients (secondary due to reduction of protein excretion). Elderly patients with diabetes melitus, coronary heart disease or peripheral vascular occlusion are at risk for deterioration of kidney function due to a high frequency of renal artery stenosis in these patients. In patients with renal insufficiency dose reduction of ACE inhibitors is necessary (exception: fosinopril) but more important is the risk for development of hyperkalemia. Patients at risk for renal artery stenosis and patients pretreated with diuretics should receive a low ACE inhibitor dosage initially ("start low - go slow"). For compliance reasons once daily ACE inhibitor dosage is recommended.

  5. Effect of extrusion process on antioxidant and ACE inhibition properties from bovine haemoglobin concentrate hydrolysates incorporated into expanded maize products.

    PubMed

    Cian, Raúl E; Luggren, Pablo; Drago, Silvina R

    2011-11-01

    Extrusion process has been widely used for the development of many functional foods. The aim of this study was to assess the effect of extrusion process on antioxidant and angiotensin-converting enzyme (ACE) inhibition properties from bovine haemoglobin concentrate (BHC) hydrolysates (P, FC, PF and FCF). Extrusion was carried out with a Brabender single screw extruder. The ACE inhibition and the antioxidant capacity (AC) were estimated by the inhibition of the ACE and ABTS+√ radical cation expressed as Trolox equivalent antioxidant capacity (TEAC), respectively. The ACE inhibition and TEAC values from hydrolysates were significantly higher than that from BHC. The highest ACE inhibition corresponded to P hydrolysate and the highest TEAC corresponded to PF and FCF hydrolysates. The ACE inhibition and AC from extruded products with added hydrolysates were higher than that from maize control; however, the extrusion process modified both ACE inhibition and AC formerly present in hydrolysates.

  6. Differential downregulation of ACE2 by the spike proteins of severe acute respiratory syndrome coronavirus and human coronavirus NL63.

    PubMed

    Glowacka, Ilona; Bertram, Stephanie; Herzog, Petra; Pfefferle, Susanne; Steffen, Imke; Muench, Marcus O; Simmons, Graham; Hofmann, Heike; Kuri, Thomas; Weber, Friedemann; Eichler, Jutta; Drosten, Christian; Pöhlmann, Stefan

    2010-01-01

    The human coronaviruses (CoVs) severe acute respiratory syndrome (SARS)-CoV and NL63 employ angiotensin-converting enzyme 2 (ACE2) for cell entry. It was shown that recombinant SARS-CoV spike protein (SARS-S) downregulates ACE2 expression and thereby promotes lung injury. Whether NL63-S exerts a similar activity is yet unknown. We found that recombinant SARS-S bound to ACE2 and induced ACE2 shedding with higher efficiency than NL63-S. Shedding most likely accounted for the previously observed ACE2 downregulation but was dispensable for viral replication. Finally, SARS-CoV but not NL63 replicated efficiently in ACE2-positive Vero cells and reduced ACE2 expression, indicating robust receptor interference in the context of SARS-CoV but not NL63 infection.

  7. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS.

    PubMed

    Patel, Vaibhav B; Clarke, Nicola; Wang, Zuocheng; Fan, Dong; Parajuli, Nirmal; Basu, Ratnadeep; Putko, Brendan; Kassiri, Zamaneh; Turner, Anthony J; Oudit, Gavin Y

    2014-01-01

    Angiotensin converting enzyme (ACE) 2 is a key negative regulator of the renin-angiotensin system where it metabolizes angiotensin (Ang) II into Ang 1-7. We hypothesize that Ang II suppresses ACE2 by increasing TNF-α converting enzyme (TACE) activity and ACE2 cleavage. Ang II infusion (1.5 mg/kg/day) in wild-type mice for 2 weeks resulted in substantial decrease in myocardial ACE2 protein levels and activity with corresponding increase in plasma ACE2 activity, prevented by AT1R blockade. Ang II resulted in AT1R-mediated increase in myocardial TACE expression and activity, and membrane translocation of TACE. Ang II treatment in Huh7 cells exhibited AT1R-dependent metalloproteinase mediated shedding of ACE2 while transfection with siTACE prevented shedding of ACE2; cardiomyocyte-specific deletion of TACE also prevented shedding of ACE2. Reactive oxygen species played a key role since p47(phox)KO mice were resistant to Ang II-induced TACE phosphorylation and activation with preservation of myocardial ACE2 which dampened Ang II-induced cardiac dysfunction and hypertrophy. In conclusion, Ang II induces ACE2 shedding by promoting TACE activity as a positive feedback mechanism whereby Ang II facilitates the loss of its negative regulator, ACE2. In HF, elevated plasma ACE2 activity likely represents loss of the protective effects of ACE2 in the heart. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. Distribution of Angiotensin-1 Converting Enzyme Insertion/Deletion and α-Actinin-3 Codon 577 Polymorphisms in Turkish Male Soccer Players.

    PubMed

    Ulucan, Korkut; Sercan, Canan; Biyikli, Türker

    2015-01-01

    Angiotensin-1 converting enzyme (ACE) gene and α-actinin-3 (ACTN3) gene polymorphisms are considered to be the most important candidate genes for genetic predisposition to human athletic performance. In the present study, we aimed to analyze the distribution of ACE and ACTN3 polymorphisms for the first time in male Turkish soccer players. In this prospective study, our cohort consisted of 25 professional players, all with Turkish ancestry. Polymerase chain reaction (PCR)-restriction length polymorphism was used for the characterization of the genotype of ACTN3 and single PCR for ACE. For ACE genotype, 16%, 44%, and 40% of the players had insertion/insertion (II), insertion/deletion (ID), and deletion/deletion (DD) genotypes, respectively, whereas 20% had XX, 36% had RX, and 44% had RR genotypes for ACTN3. When we examined the allelic percentages, for ACE, D allele was recorded as 62 and I as 38, and for ACTN3, R allele was 62 and X was 38. Our results were in agreement with the previous reports, indicating the presence of ACTN3 D and ACE X allele in soccer players. We suggest that ACE and ACTN3 genotypes are important biomarkers for genetic counseling for the individuals who are prone to be successful soccer players.

  9. [Gene mining of sulfur-containing amino acid metabolic enzymes in soybean].

    PubMed

    Qiu, Hongmei; Hao, Wenyuan; Gao, Shuqin; Ma, Xiaoping; Zheng, Yuhong; Meng, Fanfan; Fan, Xuhong; Wang, Yang; Wang, Yueqiang; Wang, Shuming

    2014-09-01

    The genes of sulfur-containing amino acid synthetases in soybean are essential for the synthesis of sulfur-containing amino acids. Gene mining of these enzymes is the basis for the molecular assistant breeding of high sulfur-containing amino acids in soybean. In this study, using software BioMercator2.1, 113 genes of sulfur-containing amino acid enzymes and 33 QTLs controlling the sulfur-containing amino acids content were mapped onto Consensus Map 4.0, which was integrated by genetic and physical maps of soybean. Sixteen candidate genes associated to the synthesis of sulfur-containing amino acids were screened based on the synteny between gene loci and QTLs, and the effect values of QTLs. Through a bioinformatic analysis of the copy number, SNP information, and expression profile of candidate genes, 12 related enzyme genes were identified and mapped on 8 linkage groups, such as D1a, M, A2, K, and G. The genes corresponding to QTL regions can explain 6%?38.5% genetic variation of sulfur-containing amino acids, and among them, the indirect effect values of 9 genes were more than 10%. These 12 genes were involved in sulfur-containing amino acid metabolism and were highly expressed in the cotyledons and flowers, showing an abundance of SNPs. These genes can be used as candidate genes for the development of functional markers, and it will lay a foundation for molecular design breeding in soybean.

  10. Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position.

    PubMed

    Heffernan, S M; Kilduff, L P; Erskine, R M; Day, S H; McPhee, J S; McMahon, G E; Stebbings, G K; Neale, J P H; Lockey, S J; Ribbans, W J; Cook, C J; Vance, B; Raleigh, S M; Roberts, C; Bennett, M A; Wang, G; Collins, M; Pitsiladis, Y P; Williams, A G

    2016-03-01

    We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ(2) and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ(2) = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ(2) = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics.

  11. Association of ACTN3 R577X but not ACE I/D gene variants with elite rugby union player status and playing position

    PubMed Central

    Kilduff, L. P.; Erskine, R. M.; Day, S. H.; McPhee, J. S.; McMahon, G. E.; Stebbings, G. K.; Neale, J. P. H.; Lockey, S. J.; Ribbans, W. J.; Cook, C. J.; Vance, B.; Raleigh, S. M.; Roberts, C.; Bennett, M. A.; Wang, G.; Collins, M.; Pitsiladis, Y. P.; Williams, A. G.

    2016-01-01

    We aimed to quantify the ACE I/D and ACTN3 R577X (rs1815739) genetic variants in elite rugby athletes (rugby union and league) and compare genotype frequencies to controls and between playing positions. The rugby athlete cohort consisted of 507 Caucasian men, including 431 rugby union athletes that for some analyses were divided into backs and forwards and into specific positional groups: front five, back row, half backs, centers, and back three. Controls were 710 Caucasian men and women. Real-time PCR of genomic DNA was used to determine genotypes using TaqMan probes and groups were compared using χ2 and odds ratio (OR) statistics. Correction of P values for multiple comparisons was according to Benjamini-Hochberg. There was no difference in ACE I/D genotype between groups. ACTN3 XX genotype tended to be underrepresented in rugby union backs (15.7%) compared with forwards (24.8%, P = 0.06). Interestingly, the 69 back three players (wings and full backs) in rugby union included only six XX genotype individuals (8.7%), with the R allele more common in the back three (68.8%) than controls (58.0%; χ2 = 6.672, P = 0.04; OR = 1.60) and forwards (47.5%; χ2 = 11.768, P = 0.01; OR = 2.00). Association of ACTN3 R577X with playing position in elite rugby union athletes suggests inherited fatigue resistance is more prevalent in forwards, while inherited sprint ability is more prevalent in backs, especially wings and full backs. These results also demonstrate the advantage of focusing genetic studies on a large cohort within a single sport, especially when intrasport positional differences exist, instead of combining several sports with varied demands and athlete characteristics. PMID:26757799

  12. Human Genetic Disorders Caused by Mutations in Genes Encoding Biosynthetic Enzymes for Sulfated Glycosaminoglycans*

    PubMed Central

    Mizumoto, Shuji; Ikegawa, Shiro; Sugahara, Kazuyuki

    2013-01-01

    A number of genetic disorders are caused by mutations in the genes encoding glycosyltransferases and sulfotransferases, enzymes responsible for the synthesis of sulfated glycosaminoglycan (GAG) side chains of proteoglycans, including chondroitin sulfate, dermatan sulfate, and heparan sulfate. The phenotypes of these genetic disorders reflect disturbances in crucial biological functions of GAGs in human. Recent studies have revealed that mutations in genes encoding chondroitin sulfate and dermatan sulfate biosynthetic enzymes cause various disorders of connective tissues. This minireview focuses on growing glycobiological studies of recently described genetic diseases caused by disturbances in biosynthetic enzymes for sulfated GAGs. PMID:23457301

  13. Regulation of Aspergillus genes encoding plant cell wall polysaccharide-degrading enzymes; relevance for industrial production.

    PubMed

    de Vries, R P

    2003-03-01

    The genus Aspergillus is widely used for the production of plant cell wall polysaccharide-degrading enzymes. The range of enzymes purified from these fungi covers nearly every function required for the complete degradation of cellulose, xyloglucan, xylan, galacto(gluco)mannan and pectin. This paper describes the Aspergillus enzymes involved in the degradation of these polysaccharides and discusses the regulatory systems involved in the expression of the genes encoding these proteins. The latter is of major importance in the large-scale production of these enzymes for industrial applications.

  14. Apelin is a positive regulator of ACE2 in failing hearts

    PubMed Central

    Sato, Teruki; Suzuki, Takashi; Watanabe, Hiroyuki; Kadowaki, Ayumi; Fukamizu, Akiyoshi; Liu, Peter P.; Kimura, Akinori; Ito, Hiroshi; Penninger, Josef M.; Imai, Yumiko; Kuba, Keiji

    2013-01-01

    Angiotensin converting enzyme 2 (ACE2) is a negative regulator of the renin-angiotensin system (RAS), catalyzing the conversion of Angiotensin II to Angiotensin 1-7. Apelin is a second catalytic substrate for ACE2 and functions as an inotropic and cardioprotective peptide. While an antagonistic relationship between the RAS and apelin has been proposed, such functional interplay remains elusive. Here we found that ACE2 was downregulated in apelin-deficient mice. Pharmacological or genetic inhibition of angiotensin II type 1 receptor (AT1R) rescued the impaired contractility and hypertrophy of apelin mutant mice, which was accompanied by restored ACE2 levels. Importantly, treatment with angiotensin 1-7 rescued hypertrophy and heart dysfunctions of apelin-knockout mice. Moreover, apelin, via activation of its receptor, APJ, increased ACE2 promoter activity in vitro and upregulated ACE2 expression in failing hearts in vivo. Apelin treatment also increased cardiac contractility and ACE2 levels in AT1R-deficient mice. These data demonstrate that ACE2 couples the RAS to the apelin system, adding a conceptual framework for the apelin-ACE2–angiotensin 1-7 axis as a therapeutic target for cardiovascular diseases. PMID:24177423

  15. CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice.

    PubMed

    Nunes-Souza, Valéria; Alenina, Natalia; Qadri, Fatimunnisa; Penninger, Josef M; Santos, Robson Augusto S; Bader, Michael; Rabelo, Luiza A

    2016-01-01

    Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2(-/y)) mice. Methods. Male C57BL/6 and ACE2(-/y) mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2(-/y) mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2(-/y) mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2(-/y) mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2(-/y) mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis.

  16. CD36/Sirtuin 1 Axis Impairment Contributes to Hepatic Steatosis in ACE2-Deficient Mice

    PubMed Central

    Qadri, Fatimunnisa; Penninger, Josef M.; Santos, Robson Augusto S.; Bader, Michael

    2016-01-01

    Background and Aims. Angiotensin converting enzyme 2 (ACE2) is an important component of the renin-angiotensin system. Since angiotensin peptides have been shown to be involved in hepatic steatosis, we aimed to evaluate the hepatic lipid profile in ACE2-deficient (ACE2−/y) mice. Methods. Male C57BL/6 and ACE2−/y mice were analyzed at the age of 3 and 6 months for alterations in the lipid profiles of plasma, faeces, and liver and for hepatic steatosis. Results. ACE2−/y mice showed lower body weight and white adipose tissue at all ages investigated. Moreover, these mice had lower levels of cholesterol, triglycerides, and nonesterified fatty acids in plasma. Strikingly, ACE2−/y mice showed high deposition of lipids in the liver. Expression of CD36, a protein involved in the uptake of triglycerides in liver, was increased in ACE2−/y mice. Concurrently, these mice exhibited an increase in hepatic oxidative stress, evidenced by increased lipid peroxidation and expression of uncoupling protein 2, and downregulation of sirtuin 1. ACE2−/y mice also showed impairments in glucose metabolism and insulin signaling in the liver. Conclusions. Deletion of ACE2 causes CD36/sirtuin 1 axis impairment and thereby interferes with lipid homeostasis, leading to lipodystrophy and steatosis. PMID:28101297

  17. Gene polymorphisms of fibrinolytic enzymes in coal workers' pneumoconiosis

    SciTech Connect

    Chang, L.C.; Tseng, J.C.; Hua, C.C.; Liu, Y.C.; Shieh, W.B.; Wu, H.P.

    2006-03-15

    The authors assessed the gene polymorphisms of missense C/T polymorphism in exon 6 of the urokinase-plasminogen activator (PLAU) gene (PLAU P141L), A/u-repeat in intron 8 of the tissue-type plasminogen activator (PLAT) gene (PLAT TPA25 Alu insertion), and 4G/5G in the promoter region of the serine proteinase inhibitor, clade E (SERPINE) or plasminogen activator inhibitor type 1 gene (SERPINE1 -675 4G/5G) in 153 healthy volunteers and 154 retired coal miners with coal miners' pneumoconiosis (CWP). The CWP subjects included 94 individuals with simple pneumoconiosis and 60 individuals with progressive massive fibrosis presenting with worse pulmonary function. The distributions of genotypes of these three genes did not differ between the control and CWP subjects or between subjects with simple pneumoconiosis and those with progressive massive fibrosis. However, by assessing duration of work and its interaction with genotypes by means of logistic regression, the authors found the missense C/T polymorphism in exon 6 of the PLAU gene to be an effect modifier of the association between work duration and the development of progressive massive fibrosis.

  18. Organization and control of genes encoding catabolic enzymes in Rhizobiaceae

    SciTech Connect

    Parke, D.; Ornston, L.N.

    1993-03-01

    Rhizobiaceae, a diverse bacterial group comprising rhizobia and agrobacteria, symbiotic partnership with plants form nitrogen-fixing nodules on plant roots or are plant pathogens. Phenolic compounds produced by plants serve as inducers of rhizobial nodulation genes and agrobacterial virulence genes reflect their capacity to utilize numerous aromatics, including phenolics, as a source of carbon and energy. In many microbes the aerobic degradation of numerous aromatic compounds to tricarboxylic acid cycle intermediates is achieved by the [beta]-ketoadipate pathway. Our initial studies focused on the organization and regulation of the ketoadipate pathway in Agrobacterium tumefaciens. We have cloned, identified and characterized a novel regulatory gene that modulates expression of an adjacent pca (protocatechuate) structural gene, pcaD. Regulation of pcaD is mediated by the regulatory gene, termed pcaQ, in concert with the intermediate [beta]-carboxy-cis,cis-muconate. [beta]-carboxy-cis,cismuconate is an unstable chemical, not marketed commercially, and it is unlikely to permeate Escherichia coli cells if supplied in media. Because of these factors, characterization of pcaQ in E. coli required an in vivo delivery system for [beta]-carboxycis,cis-muconate. This was accomplished by designing an E. coli strain that expressed an Acinetobacter calcoaceticus pcaA gene for conversion of protocatechuate to [beta]-carboxy-cis,cis-muconate.

  19. Bioactive peptides: are there more antihypertensive mechanisms beyond ACE inhibition?

    PubMed

    Marques, Claudia; Amorim, Maria Manuela; Pereira, Joana Odila; Pintado, Manuela Estevez; Moura, Daniel; Calhau, Conceicao; Pinheiro, Helder

    2012-01-01

    Diet has a high relevance in health. Hypertension is a major risk factor for cardiovascular diseases and has an important impact on public health, and consequently on countries economy. Scientific research gathered strong evidence about the role of several dietary factors either in etiology or in treatment/prevention of these diseases. Peptides from different food matrices have been studied, and indicated as compounds with particular interest in the context of hypertension. The classical approach involves the identification of peptides with an in vitro ACE inhibitory activity and the assumption that the observed in vivo effects are due to this enzyme blockade. However, in some cases the potency of ACE blockade does not correlate with the antihypertensive activity in vivo. This paper reviews the current literature that identifies mechanisms of action, other than ACE inhibition, that might explain antihypertensive effects of biologically active peptides from different food sources.

  20. Brain ACE2 shedding contributes to the development of neurogenic hypertension

    PubMed Central

    Chhabra, Kavaljit H.; Lazartigues, Eric

    2015-01-01

    Rationale Over-activity of the brain Renin Angiotensin System (RAS) is a major contributor to neurogenic hypertension. While over-expression of Angiotensin-Converting Enzyme type 2 (ACE2) has been shown to be beneficial in reducing hypertension by transforming Angiotensin (Ang)-II into Ang-(1-7), several groups have reported decreased brain ACE2 expression and activity during the development of hypertension. Objective We hypothesized that ADAM17-mediated ACE2 shedding results in decreased membrane-bound ACE2 in the brain, thus promoting the development of neurogenic hypertension. Methods and Results To test this hypothesis, we used the DOCA-salt model of neurogenic hypertension in non-transgenic (NT) and syn-hACE2 mice over-expressing ACE2 in neurons. DOCA-salt treatment in NT mice led to significant increases in blood pressure, hypothalamic Ang-II levels, inflammation, impaired baroreflex sensitivity, autonomic dysfunction, as well as decreased hypothalamic ACE2 activity and expression, while these changes were blunted or prevented in syn-hACE2 mice. In addition, reduction of ACE2 expression and activity in the brain paralleled a rise in ACE2 activity in the cerebrospinal fluid of NT mice following DOCA-salt treatment and was accompanied by enhanced ADAM17 expression and activity in the hypothalamus. Chronic knockdown of ADAM17 in the brain blunted the development of hypertension and restored ACE2 activity and baroreflex function. Conclusions Our data provide the first evidence that ADAM17-mediated shedding impairs brain ACE2 compensatory activity, thus contributing to the development of neurogenic hypertension. PMID:24014829

  1. Prevalence of the angiotensin I converting enzyme insertion/deletion polymorphism, plasma angiotensin converting enzyme activity, and left ventricular mass in a normotensive Chilean population.

    PubMed

    Jalil, J E; Piddo, A M; Cordova, S; Chamorro, G; Braun, S; Jalil, R; Vega, J; Jadue'P, L; Lavandero, S; Lastra, P

    1999-07-01

    The aim of this study was to estimate the prevalence of the different alleles of the angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and associated plasma ACE activity, as well as cardiac echocardiographic structure, in a healthy Chilean population. We selected 117 healthy normotensive subjects (aged 45 to 60 years, middle socioeconomic status, nonobese, and nondiabetic) from a population-based study concerning the prevalence of risk factors for chronic diseases (Conjunto de Acciones Para la Reducción Multifactorial de las Enfermedades no Transmisibles [CARMEN]). The frequencies of the I and D alleles were 0.57 and 0.43, respectively. Mean plasma ACE activity was 15.3 +/- 3.9 U/mL. Compared with subjects with the II genotype, plasma ACE activity was significantly higher in subjects with the ID and DD genotypes with no difference between them. No correlation was observed between blood pressure and plasma ACE activity. Among the three different genotypes there was no difference in left ventricular (LV) dimensions or in LV mass. No correlation between plasma ACE activity and LV mass was observed for either gender or different genotypes. Multivariate linear regression analysis using LV mass and LV mass index as dependent variables showed independent effects (P < .05) for gender (higher LV mass in men) and diastolic blood pressure, but not for the DD genotype. In conclusion, in this population, the presence of the D allele on the ACE gene determined higher circulating ACE activity. However, in this normotensive healthy population, male gender and diastolic blood pressure, but not the presence of the D allele, were associated with increased LV mass.

  2. Gene Expression Variability in Human Hepatic Drug Metabolizing Enzymes and Transporters

    PubMed Central

    Yang, Lun; Price, Elvin T.; Chang, Ching-Wei; Li, Yan; Huang, Ying; Guo, Li-Wu; Guo, Yongli; Kaput, Jim; Shi, Leming; Ning, Baitang

    2013-01-01

    Interindividual variability in the expression of drug-metabolizing enzymes and transporters (DMETs) in human liver may contribute to interindividual differences in drug efficacy and adverse reactions. Published studies that analyzed variability in the expression of DMET genes were limited by sample sizes and the number of genes profiled. We systematically analyzed the expression of 374 DMETs from a microarray data set consisting of gene expression profiles derived from 427 human liver samples. The standard deviation of interindividual expression for DMET genes was much higher than that for non-DMET genes. The 20 DMET genes with the largest variability in the expression provided examples of the interindividual variation. Gene expression data were also analyzed using network analysis methods, which delineates the similarities of biological functionalities and regulation mechanisms for these highly variable DMET genes. Expression variability of human hepatic DMET genes may affect drug-gene interactions and disease susceptibility, with concomitant clinical implications. PMID:23637747

  3. The absence of intrarenal ACE protects against hypertension

    PubMed Central

    Gonzalez-Villalobos, Romer A.; Janjoulia, Tea; Fletcher, Nicholas K.; Giani, Jorge F.; Nguyen, Mien T.X.; Riquier-Brison, Anne D.; Seth, Dale M.; Fuchs, Sebastien; Eladari, Dominique; Picard, Nicolas; Bachmann, Sebastian; Delpire, Eric; Peti-Peterdi, Janos; Navar, L. Gabriel; Bernstein, Kenneth E.; McDonough, Alicia A.

    2013-01-01

    Activation of the intrarenal renin-angiotensin system (RAS) can elicit hypertension independently from the systemic RAS. However, the precise mechanisms by which intrarenal Ang II increases blood pressure have never been identified. To this end, we studied the responses of mice specifically lacking kidney angiotensin-converting enzyme (ACE) to experimental hypertension. Here, we show that the absence of kidney ACE substantially blunts the hypertension induced by Ang II infusion (a model of high serum Ang II) or by nitric oxide synthesis inhibition (a model of low serum Ang II). Moreover, the renal responses to high serum Ang II observed in wild-type mice, including intrarenal Ang II accumulation, sodium and water retention, and activation of ion transporters in the loop of Henle (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases SPAK and OSR1, were effectively prevented in mice that lack kidney ACE. These findings demonstrate that ACE metabolism plays a fundamental role in the responses of the kidney to hypertensive stimuli. In particular, renal ACE activity is required to increase local Ang II, to stimulate sodium transport in loop of Henle and the distal nephron, and to induce hypertension. PMID:23619363

  4. The absence of intrarenal ACE protects against hypertension.

    PubMed

    Gonzalez-Villalobos, Romer A; Janjoulia, Tea; Fletcher, Nicholas K; Giani, Jorge F; Nguyen, Mien T X; Riquier-Brison, Anne D; Seth, Dale M; Fuchs, Sebastien; Eladari, Dominique; Picard, Nicolas; Bachmann, Sebastian; Delpire, Eric; Peti-Peterdi, Janos; Navar, L Gabriel; Bernstein, Kenneth E; McDonough, Alicia A

    2013-05-01

    Activation of the intrarenal renin-angiotensin system (RAS) can elicit hypertension independently from the systemic RAS. However, the precise mechanisms by which intrarenal Ang II increases blood pressure have never been identified. To this end, we studied the responses of mice specifically lacking kidney angiotensin-converting enzyme (ACE) to experimental hypertension. Here, we show that the absence of kidney ACE substantially blunts the hypertension induced by Ang II infusion (a model of high serum Ang II) or by nitric oxide synthesis inhibition (a model of low serum Ang II). Moreover, the renal responses to high serum Ang II observed in wild-type mice, including intrarenal Ang II accumulation, sodium and water retention, and activation of ion transporters in the loop of Henle (NKCC2) and distal nephron (NCC, ENaC, and pendrin) as well as the transporter activating kinases SPAK and OSR1, were effectively prevented in mice that lack kidney ACE. These findings demonstrate that ACE metabolism plays a fundamental role in the responses of the kidney to hypertensive stimuli. In particular, renal ACE activity is required to increase local Ang II, to stimulate sodium transport in loop of Henle and the distal nephron, and to induce hypertension.

  5. Clinical Inquiry: Do ACE inhibitors or ARBs help prevent kidney disease in patients with diabetes and normal BP?

    PubMed

    Trietley, Gregory S; Wilson, Stephen A; Chaudhri, Parul; Payette, Nicole; Higbea, Ashley; Nashelsky, Joan

    2017-04-01

    Yes for angiotensin-converting enzyme (ACE) inhibitors, no for angiotensin receptor blockers (ARBs). A 2011 meta-analysis of 5 RCTs (total 2975 patients) that compared ACE inhibitor therapy with placebo in diabetic patients without hypertension and albuminuria found that ACE inhibitors reduced the risk of new-onset microalbuminuria or macroalbuminuria by 18% (relative risk [RR]=0.82; 95% confidence interval [CI], 0.73-0.92).

  6. Radiation Exposure Alters Expression of Metabolic Enzyme Genes in Mice

    NASA Technical Reports Server (NTRS)

    Wotring, V. E.; Mangala, L. S.; Zhang, Y.; Wu, H.

    2011-01-01

    Most administered pharmaceuticals are metabolized by the liver. The health of the liver, especially the rate of its metabolic enzymes, determines the concentration of circulating drugs as well as the duration of their efficacy. Most pharmaceuticals are metabolized by the liver, and clinically-used medication doses are given with normal liver function in mind. A drug overdose can result in the case of a liver that is damaged and removing pharmaceuticals from the circulation at a rate slower than normal. Alternatively, if liver function is elevated and removing drugs from the system more quickly than usual, it would be as if too little drug had been given for effective treatment. Because of the importance of the liver in drug metabolism, we want to understand the effects of spaceflight on the enzymes of the liver and exposure to cosmic radiation is one aspect of spaceflight that can be modeled in ground experiments. Additionally, it has been previous noted that pre-exposure to small radiation doses seems to confer protection against later and larger radiation doses. This protective power of pre-exposure has been called a priming effect or radioadaptation. This study is an effort to examine the drug metabolizing effects of radioadaptation mechanisms that may be triggered by early exposure to low radiation doses.

  7. Intrapulmonary activation of the angiotensin-converting enzyme type 2/angiotensin 1-7/G-protein-coupled Mas receptor axis attenuates pulmonary hypertension in Ren-2 transgenic rats exposed to chronic hypoxia.

    PubMed

    Hampl, V; Herget, J; Bíbová, J; Baňasová, A; Husková, Z; Vaňourková, Z; Jíchová, Š; Kujal, P; Vernerová, Z; Sadowski, J; Červenka, L

    2015-01-01

    The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT₁) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT₁receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT₁receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

  8. RNAi of ace1 and ace2 in Blattella germanica reveals their differential contribution to acetylcholinesterase activity and sensitivity to insecticides.

    PubMed

    Revuelta, L; Piulachs, M D; Bellés, X; Castañera, P; Ortego, F; Díaz-Ruíz, J R; Hernández-Crespo, P; Tenllado, F

    2009-12-01

    Cyclorrhapha insect genomes contain a single acetylcholinesterase (AChE) gene while other insects contain at least two ace genes (ace1 and ace2). In this study we tested the hypothesis that the two ace paralogous from Blattella germanica have different contributions to AChE activity, using RNA interference (RNAi) to knockdown each one individually. Paralogous-specific depletion of Bgace transcripts was evident in ganglia of injected cockroaches, although the effects at the protein level were less pronounced. Using spectrophotometric and zymogram measurements, we obtained evidence that BgAChE1 represents 65-75% of the total AChE activity in nerve tissue demonstrating that ace1 encodes a predominant AChE. A significant increase in sensitivity of Bgace1-interfered cockroaches was observed after 48 h of exposure to chlorpyrifos. In contrast, Bgace2 knockdown had a negligible effect on mortality to this organophosphate. These results point out a key role, qualitative and/or quantitative, of AChE1 as target of organophosphate insecticides in this species. Silencing the expression of Bgace1 but not Bgace2 also produced an increased mortality in insects when synergized with lambda-cyhalothrin, a situation which resembles the synergistic effects observed between organophosphates and pyrethroids. Gene silencing of ace genes by RNAi offers an exciting approach for examining a possible functional differentiation in ace paralogous.

  9. Association of angiotensin I converting enzyme, angiotensin II type 1 receptor and angiotensin I converting enzyme 2 gene polymorphisms with the dyslipidemia in type 2 diabetic patients of Chinese Han origin.

    PubMed

    Xu, Y; Bao, Q; He, B; Pan, Y; Zhang, R; Mao, X; Tang, Z; Qu, L; Zhu, C; Tian, F; Wang, S

    2012-04-01

    To investigate whether the genetic polymorphisms in the angiotensin I converting enzyme (ACE) (insertion/ deletion, or I/D), angiotensin II type 1 receptor (AT1R) (rs5186), and ACE2 (rs2285666) could be associated with dyslipidemia in Type 2 diabetic (T2D) patients of Chinese Han origin. The above 3 polymorphisms were genotyped in a total of 282 patients with T2D and dyslipidemia (Group A), 182 patients with T2D but without dyslipidemia (Group B), and 324 healthy controls. The association between a certain polymorphism and each group was assessed by an odds ratio (OR). The D allele of the ACE (I/D) was significantly associated with the risk of T2D accompanying dyslipidemia between group A and controls [OR=1.37, 95% confidence interval (CI)=1.08-1.74; p=0.010], and significant association of the D allele with dyslipidemia was also observed in diabetic patients (OR=1.88, 95% CI=1.40-2.54; p<0.001). Furthermore, the ID genotype had a decreased risk of developing T2D without dyslipidemia as compared with controls (OR=0.52, 95% CI=0.32-0.82; p=0.0060). The distributions of the AT1R (rs5186) and ACE2 (rs2285666) genotypes and alleles did not differ between T2D patients with or without dyslipidemia and the controls. This study demonstrates that the ACE (I/D) polymorphism is associated with T2D, regardless of the absence or presence of dyslipidemia. The polymorphisms in the AT1R (rs5186) and ACE2 (rs2285666) seem to play lesser roles in the development of T2D.

  10. Influence of Angiotensin-Converting-Enzyme Gene Polymorphism on Echocardiographic Data of Patients with Ischemic Heart Failure.

    PubMed

    Duque, Gustavo Salgado; Silva, Dayse Aparecida da; Albuquerque, Felipe Neves de; Schneider, Roberta Siuffo; Gimenez, Alinne; Pozzan, Roberto; Rocha, Ricardo Mourilhe; Albuquerque, Denilson Campos de

    2016-11-01

    Association between angiotensin-converting-enzyme (ACE) gene polymorphisms and different clinical and echocardiographic outcomes has been described in patients with heart failure (HF) and coronary artery disease. Studying the genetic profile of the local population with both diseases is necessary to assess the occurrence of that association. To assess the frequency of ACE gene polymorphisms in patients with ischemic HF in a Rio de Janeiro population, as well as its association with echocardiographic findings. Genetic assessment of I/D ACE polymorphism in association with clinical, laboratory and echocardiographic analysis of 99 patients. The allele frequency was: 53 I alleles, and 145 D alleles. Genotype frequencies were: 49.5% DD; 47.48% DI; 3.02% II. Drug treatment was optimized: 98% on beta-blockers, and 84.8% on ACE inhibitors or angiotensin-receptor blocker. Echocardiographic findings: difference between left ventricular diastolic diameters (ΔLVDD) during follow-up: 2.98±8.94 (DD) vs. 0.68±8.12 (DI) vs. -11.0±7.00 (II), p=0.018; worsening during follow-up of the LV systolic diameter (LVSD): 65.3% DD vs. 19.0% DI vs. 0.0% II, p=0.01; of the LV diastolic diameter (LVDD): 65.3% DD vs. 46.8% DI vs. 0.0% II, p=0.03; and of the LV ejection fraction (LVEF): 67.3% DD vs. 40.4% DI vs. 33.3% II, p=0.024. Correlated with D allele: ΔLVEF, ΔLVSD, ΔLVDD. More DD genotype patients had worsening of the LVEF, LVSD and LVDD, followed by DI genotype patients, while II genotype patients had the best outcome. The same pattern was observed for ΔLVDD. Associação entre polimorfismos genéticos da enzima conversora da angiotensina (ECA) e diferentes evoluções clínicas e ecocardiográficas foi descrita em pacientes com insuficiência cardíaca (IC) e coronariopatia. O estudo do perfil genético da população local com as duas doenças torna-se necessário para verificar a ocorrência dessa associação. Avaliar a frequência dos polimorfismos genéticos da ECA em

  11. Genetically-reduced serum ACE activity might be a causal risk factor for obstructive sleep apnea syndrome: A meta-analysis

    PubMed Central

    He, Lan; Wang, Bin; Lang, Wei-Ya; Xue, Jing; Zhao, Da-Long; Li, Guo-Feng; Zheng, Li-Hong; Pan, Hong-Ming

    2015-01-01

    We meta-analytically summarized the associations of angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with ACE activity and obstructive sleep apnea syndrome (OSAS) to see whether ACE activity is causally associated with OSAS. Literature search and data abstraction were done in duplicate. Sixteen articles including 2060 OSAS patients and 1878 controls were summarized. Overall, no significance was observed for the association of I/D polymorphism with OSAS, whereas carriers of II genotype (weighted mean difference or WMD, 95% confidence interval or CI, P: −11.976, −17.168 to −6.783, <0.001) or I allele (−9.842, −14.766 to −4.918, <0.001) had a lower level of serum ACE activity compared with DD genotype carriers, respectively. In subgroup analyses, carriers of II genotype were 3.806 times more likely to develop OSAS (95% CI, P: 1.865 to 7.765, <0.001) in OSAS patients with hypertension, without heterogeneity. Mendelian randomization analysis indicated there was 37.4% (95% CI: 1.115 to 3.142) and 32.4% (1.106 to 2.845) increased risk of OSAS by a reduction of 1 U/L in ACE activity for the II genotype and I allele carriers versus DD genotype carriers, respectively. There was no observable publication bias. Collectively, genetically-reduced serum ACE activity might be a causal risk factor for OSAS. PMID:26486181

  12. Halloween genes encode P450 enzymes that mediate steroid hormone biosynthesis in Drosophila melanogaster.

    PubMed

    Gilbert, Lawrence I

    2004-02-27

    Mutation of members of the Halloween gene family results in embryonic lethality. We have shown that two of these genes code for enzymes responsible for specific steps in the synthesis of ecdysone, a polyhydroxylated sterol that is the precursor of the major molting hormone of all arthropods, 20-hydroxyecdysone. These two mitochondrial P450 enzymes, coded for by disembodied (dib) (CYP302A1) and shadow (sad) (CYP315A1), are the C22 and C2 hydroxylases, respectively, as shown by transfection of the gene into S2 cells and subsequent biochemical analysis. These are the last two enzymes in the ecdysone biosynthetic pathway. A third enzyme, necessary for the critical conversion of ecdysone to 20-hydroxyecdysone, the 20-monooxygenase, is encoded by shade (shd) (CYP314A1). All three enzymes are mitochondrial although shade has motifs suggesting both mitochondrial and microsomal locations. By tagging these enzymes, their subcellular location has been confirmed by confocal microscopy. Shade is present in several tissues as expected while disembodied and shadow are restricted to the ring gland. The paradigm used should allow us to define the enzymes mediating the entire ecdysteroid biosynthetic pathway.

  13. Enhanced cardioprotective effects mediated by plasmid containing the short-hairpin RNA of angiotensin converting enzyme with a biodegradable hydrogel after myocardial infarction.

    PubMed

    Wan, Wei-Guo; Jiang, Xue-Jun; Li, Xiao-Yan; Zhang, Cui; Yi, Xin; Ren, Shan; Zhang, Xian-Zheng

    2014-10-01

    The expression of foreign gene was enhanced and prolonged by sustained releasing a target gene to cells from biodegradable dextran-poly(e-caprolactone)-2-hydroxylethylmethacrylate-poly(N-isopropylacrylamide) (Dex-PCL-HEMA/PNIPAAm) hydrogel in vitro. Moreover, we have demonstrated that injection of the same hydrogel improved post-infarct ventricular remodeling. Therefore, we hypothesized that intramyocardial injection of plasmid containing the short-hairpin RNA (shRNA) of angiotensin converting enzyme (ACE) with the same hydrogel enhances the cardioprotective effects superior to either alone or after rat myocardial infarction (MI). In this study, equal volume of phosphate-buffered solution (PBS), 10 μg ACE-shRNA plasmids, hydrogel containing 10 μg negative control ACE-shRNA plasmids and hydrogel containing 10 μg ACE-shRNA plasmids were shortly injected into the infarct area of rats after MI, respectively. We found that ACE-shRNA plasmid-loaded hydrogel extended the duration of gene expression in vivo. Moreover, it was shown that direct intramyocardial injection of ACE-shRNA plasmid-loaded hydrogel significantly decreased the expression of local ACE expression, inhibited cell apoptosis, reduced infarct size, and improved cardiac function compared with the injection of either alone 30 days after MI in rats. These results suggest that injection of ACE-shRNA plasmid-loaded hydrogel into impaired myocardium obtains more cardioprotective effects than either alone in rat with MI by prolonging the gene silencing of ACE. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 3452-3458, 2014.

  14. Purine utilization by Klebsiella oxytoca M5al: genes for ring-oxidizing and -opening enzymes.

    PubMed

    Pope, Scott D; Chen, Li-Ling; Stewart, Valley

    2009-02-01

    The enterobacterium Klebsiella oxytoca uses a variety of inorganic and organic nitrogen sources, including purines, nitrogen-rich compounds that are widespread in the biosphere. We have identified a 23-gene cluster that encodes the enzymes for utilizing purines as the sole nitrogen source. Growth and complementation tests with insertion mutants, combined with sequence comparisons, reveal functions for the products of these genes. Here, we report our characterization of 12 genes, one encoding guanine deaminase and the others encoding enzymes for converting (hypo)xanthine to allantoate. Conventionally, xanthine dehydrogenase, a broadly distributed molybdoflavoenzyme, catalyzes sequential hydroxylation reactions to convert hypoxanthine via xanthine to urate. Our results show that these reactions in K. oxytoca are catalyzed by a two-component oxygenase (HpxE-HpxD enzyme) homologous to Rieske nonheme iron aromatic-ring-hydroxylating systems, such as phthalate dioxygenase. Our results also reveal previously undescribed enzymes involved in urate oxidation to allantoin, catalyzed by a flavoprotein monooxygenase (HpxO enzyme), and in allantoin conversion to allantoate, which involves allantoin racemase (HpxA enzyme). The pathway also includes the recently described PuuE allantoinase (HpxB enzyme). The HpxE-HpxD and HpxO enzymes were discovered independently by de la Riva et al. (L. de la Riva, J. Badia, J. Aguilar, R. A. Bender, and L. Baldoma, J. Bacteriol. 190:7892-7903, 2008). Thus, several enzymes in this K. oxytoca purine utilization pathway differ from those in other microorganisms. Isofunctional homologs of these enzymes apparently are encoded by other species, including Acinetobacter, Burkholderia, Pseudomonas, Saccharomyces, and Xanthomonas.

  15. [Tryptophan 7-halogenase from Pseudomonas aureofaciens ACN strain: gene cloning and sequencing and the enzyme expression].

    PubMed

    Burd', V N; van Pee, K H

    2004-01-01

    The gene of tryptophan 7-halogenase was isolated from the Pseudomonas aureofaciens ACN strain producing pyrrolnitrin, a chlorocontaining antibiotic, and sequenced. A high homology degree (over 95%) was established for the genes and the corresponding halogenases from P. aureofaciens ACN and P. fluorescens BL915. The tryptophan 7-halogenase gene was amplified by PCR, and the corresponding enzyme was expressed in Escherichia coli cells using the pBSII SK+ vector.

  16. Molecular genetics of aminoglycoside resistance genes and familial relationships of the aminoglycoside-modifying enzymes.

    PubMed Central

    Shaw, K J; Rather, P N; Hare, R S; Miller, G H

    1993-01-01

    The three classes of enzymes which inactivate aminoglycosides and lead to bacterial resistance are reviewed. DNA hybridization studies have shown that different genes can encode aminoglycoside-modifying enzymes with identical resistance profiles. Comparisons of the amino acid sequences of 49 aminoglycoside-modifying enzymes have revealed new insights into the evolution and relatedness of these proteins. A preliminary assessment of the amino acids which may be important in binding aminoglycosides was obtained from these data and from the results of mutational analysis of several of the genes encoding aminoglycoside-modifying enzymes. Recent studies have demonstrated that aminoglycoside resistance can emerge as a result of alterations in the regulation of normally quiescent cellular genes or as a result of acquiring genes which may have originated from aminoglycoside-producing organisms or from other resistant organisms. Dissemination of these genes is aided by a variety of genetic elements including integrons, transposons, and broad-host-range plasmids. As knowledge of the molecular structure of these enzymes increases, progress can be made in our understanding of how resistance to new aminoglycosides emerges. Images PMID:8385262

  17. DNA polymorphisms of apolipoprotein B and angiotensin I-converting enzyme genes and relationships with lipid levels in Italian patients with vascular dementia or Alzheimer's disease.

    PubMed

    Scacchi, R; De Bernardini, L; Mantuano, E; Vilardo, T; Donini, L M; Ruggeri, M; Gemma, A T; Pascone, R; Corbo, R M

    1998-01-01

    The distribution of three DNA polymorphisms (XbaI, EcoRI, and I/D) of the apolipoprotein B (APOB) gene, and of the I/D polymorphism of the angiotensin I-converting enzyme (ACE) gene was investigated in 53 patients with vascular dementia, in 80 patients with late-onset sporadic Alzheimer's disease, and in 153 age-matched control subjects. Furthermore, plasma total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides were measured in the three groups and the involvement of the genetic variation at APOB locus on lipid levels was determined. Major findings of this work are (1) no genotype or allele of the polymorphisms examined here seemed to be associated with vascular dementia or with Alzheimer's disease, (2) total cholesterol and LDL cholesterol levels were lower in Alzheimer's disease patients than in vascular dementia patients and in elderly controls, and (3) the dementia patients with APOB EcoRI R+R- genotype had higher total cholesterol and LDL cholesterol levels than R+R+ homozygotes.

  18. Egg-derived bioactive peptides with ACE-inhibitory properties: a literature update.

    PubMed

    Grootaert, Charlotte; Matthijs, Bea; Voorspoels, Stefan; Possemiers, Sam; Smagghe, Guy; Van Camp, John

    2017-09-25

    Egg proteins contain a wide set of peptide sequences which have an impact on cardiovascular health. Their modes-of-action involve, among others, the inhibition of angiotensin-converting enzyme (ACE) and antioxidant and anti-inflammatory properties. In this review, we focus particularly on ACE-inhibition and discuss recent findings in: (i) production methods for egg protein-derived ACE-inhibitory peptides, (ii) in vitro functionality of these peptides, (iii) their intestinal digestion and absorption in order to reach the target tissue, (iv) the impact of ACE-inhibitory egg-derived peptides in vivo and (v) future perspectives for the implementation of egg-derived ACE-inhibitory peptides as functional foods.

  19. Do ACE inhibitors all provide the same outcomes benefits in high-risk cardiovascular patients?

    PubMed

    Lala, Anu; McLaughlin, Mary Ann

    2008-08-01

    The Heart Outcomes Prevention (HOPE) trial was the first to demonstrate the benefits of the angiotensin-converting enzyme (ACE) inhibitor ramipril for high-risk cardiovascular patients. Whether the cardioprotective effects seen in HOPE and other trials are specific to distinct ACE inhibitors remains controversial. Evidence of a lack of class effect for ACE inhibitors has policy and financial implications related to reference pricing by insurers and inclusion on pharmacy formularies. Because head-to-head trials comparing the different ACE inhibitors are unforeseen, clinicians and administrators must rely on secondary-level data and observational studies. Only a handful of studies have sought to address the dispute over a class effect among ACE inhibitors, which is reviewed in this article.

  20. [Alkaline-adapted beta-mannanase of Bacillus pumilus: gene heterologous expression and enzyme characterization].

    PubMed

    Tang, Jiajie; Guo, Su; Wang, Wei; Wei, Wei; Wei, Dongzhi

    2015-11-04

    We expressed a novel alkaline-adapted beta-mannanase gene and characterized the enzyme for potential industrial applications. We obtained a mannanase gene (named man(B)) from Bacillus pumilus Nsic2 and expressed the gene man(B) in Escherichia coli and Bacillus subtilis. Furthermore, we characterized the enzyme. The gene man(B) had an open reading frame of 1104 bp that encoded a polypeptide of 367-amino-acid beta-mannanase (Man(B)). The protein sequence showed the highest identity with the beta-mannanase from B. pumilus CCAM080065. We expressed the gene man(B) in E. coli BL21 (DE3) with the enzyme activity of 11021.3 U/mL. Compared with other mannanases, Man(B) showed higher stability under alkaline conditions and was stable at pH6.0 -9.0. The specific activity of purified Man(B) was 4191 ± 107 U/mg. The K(m) and V(max) values of purified Man(B) were 35.7 mg/mL and 14.9 μmol/(mL x min), respectively. Meanwhile, we achieved recombinant protein secretion expression in B. subtilis WB800N. We achieved heterologous expression of the gene man(B) and characterized its enzyme. The alkaline-adapted Man(B) showed potential value in industrial applications due to its pH stability.

  1. Evolution of substrate specificity in a retained enzyme driven by gene loss.

    PubMed

    Juárez-Vázquez, Ana Lilia; Edirisinghe, Janaka E; Verduzco-Castro, Ernesto A; Michalska, Karolina; Wu, Chenggang; Noda-García, Lianet; Babnigg, Gyorgy; Endres, Michael; Medina-Ruíz, Sofía; Santoyo-Flores, Julián; Carrillo-Tripp, Mauricio; Ton-That, Hung; Joachimiak, Andrzej; Henry, Christopher S; Barona-Gómez, Francisco

    2017-03-31

    The connection between gene loss and the functional adaptation of retained proteins is still poorly understood. We apply phylogenomics and metabolic modeling to detect bacterial species that are evolving by gene loss, with the finding that Actinomycetaceae genomes from human cavities are undergoing sizable reductions, including loss of L-histidine and L-tryptophan biosynthesis. We observe that the dual-substrate phosphoribosyl isomerase A or priA gene, at which these pathways converge, appears to coevolve with the occurrence of trp and his genes. Characterization of a dozen PriA homologs shows that these enzymes adapt from bifunctionality in the largest genomes, to a monofunctional, yet not necessarily specialized, inefficient form in genomes undergoing reduction. These functional changes are accomplished via mutations, which result from relaxation of purifying selection, in residues structurally mapped after sequence and X-ray structural analyses. Our results show how gene loss can drive the evolution of substrate specificity from retained enzymes.

  2. [Differential expression of genes that encode glycolysis enzymes in kidney and lung cancer in humans].

    PubMed

    Oparina, N Yu; Snezhkina, A V; Sadritdinova, A F; Veselovskii, V A; Dmitriev, A A; Senchenko, V N; Mel'nikova, N V; Speranskaya, A S; Darii, M V; Stepanov, O A; Barkhatov, I M; Kudryavtseva, A V

    2013-07-01

    Glycolysis is a main catabolic pathway of glucose metabolism, accompanied by ATP synthesis. More than 30 enzymes are involved in glycolysis, and genes that encode them can be considered housekeeping genes due to the high conservatism and evolutionary antiquity of the process. We studied the expression of these genes in kidney papillary cancer and planocellular lung cancer via the bioinformatic analysis of transcriptome database and method of quantitative real time PCR. Quantitative analysis of mRNA level demonstrated that only a part ofgenes that encode glycolysis enzymes maintain relatively stable mRNA level, including the HK1, ADPGK, GPI, PGK1, and PKM2 genes in kidney papillary cancer and the ADPGK, ALDOA, GAPDH, PGK1, BPGM, ENO1, and PKM2 genes in planocellular lung cancer. The frequent increase in the mRNA expression of PFKP, ALDOA, and GAPDH genes in kidney cancer, as well as the GPI gene in lung cancer, were detected for the first time by real time PCR. For other genes, their differential expression was demonstrated; the cases of both a decrease and increase in the mRNA level were detected. Thus, several genes that can be used as control genes in transcriptome analysis by real time PCR in kidney and lung cancer, as well as a number of differentially expressed genes that can be potential oncomarkers, were identified.

  3. ALTUS Cumulus Electrification Study (ACES)

    NASA Technical Reports Server (NTRS)

    Kim, Tony; Blakeslee, Richard; Russell, Larry W. (Technical Monitor)

    2002-01-01

    The ALTUS Cumulus Electrification Study (ACES) is an uninhabited aerial vehicle (UAV)-based project that will investigate thunderstorms in the vicinity of the Florida Everglades in August 2002. ACES is being conducted to both investigate storm electrical activity and its relationship to storm morphology, and validate Tropical Rainfall Measurement Mission (TRMM) satellite measurements. In addition, as part of NASA's UAV-based science demonstration program, this project will provide a scientifically useful demonstration of the utility and promise of UAV platforms for Earth science and applications observations. Part of the demonstration involves getting approvals from the Federal Aviation Administration and the NASA airworthiness flight safety review board. ACES will employ the ALTUS II aircraft, built by General Atomics - Aeronautical Systems, Inc. Key science objectives simultaneously addressed by ACES are to: (1) investigate lightning-storm relationships, (2) study storm electrical budgets, and (3) provide Lightning Imaging Sensor validation. The ACES payload, already developed and flown on ALTUS, includes electrical, magnetic, and optical sensors to remotely characterize the lightning activity and the electrical environment within and around thunderstorms. ACES will contribute important electrical and optical measurements not available from other sources. Also, the high altitude vantage point of the UAV observing platform (up to 55,000 feet) offers a useful 'cloud-top' perspective. By taking advantage of its slow flight speed (70 to 100 knots), long endurance, and high altitude flight, the ALTUS will be flown near, and when possible, above (but never into) thunderstorms for long periods of time, allowing investigations to be conducted over entire storm life cycles. In addition, concurrent ground-based observations will enable the UAV measurements to be more completely interpreted and evaluated in the context of the thunderstorm structure, evolution, and

  4. Angiotensin I Converting Enzyme (Kininase II) of the Brush Border of Human and Swine Intestine.

    DTIC Science & Technology

    1980-05-23

    demonstrated by bioassay. Captopril , the orally active specific inhibitor of ACE, inhibited tt6 enzyme: its I was 3 x 10_9M. Antibody to swine kidney ACE...interference in the functions of this enzyme may occur with chronic captopril therapy. K ngiotensir Iconverting enzyme (ACE; dipeptidyl carboxypeptidase; E.C...intestinal brush border (l0).+ These studies were also prompted by the use of the specific inhibitor of ACE, SQ 14225 or captopril , on a large scale in

  5. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice

    PubMed Central

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2-/-) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2-/- mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2-/- mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2-/- mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2-/- mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury. PMID:27019629

  6. Alternative Roles of STAT3 and MAPK Signaling Pathways in the MMPs Activation and Progression of Lung Injury Induced by Cigarette Smoke Exposure in ACE2 Knockout Mice.

    PubMed

    Hung, Yi-Han; Hsieh, Wen-Yeh; Hsieh, Jih-Sheng; Liu, Fon-Chang; Tsai, Chin-Hung; Lu, Li-Che; Huang, Chen-Yi; Wu, Chien-Liang; Lin, Chih-Sheng

    2016-01-01

    Inflammation-mediated abnormalities in the renin-angiotensin system (RAS) and expression of matrix metalloproteinases (MMPs) are implicated in the pathogenesis of lung injury. Angiotensin converting enzyme II (ACE2), an angiotensin converting enzyme (ACE) homologue that displays antagonist effects on ACE/angiotensin II (Ang II) axis, could also play a protective role against lung diseases. However, the relationship between ACE2 and MMPs activation in lung injury is still largely unclear. The purpose of this study is to investigate whether MMPs activity could be affected by ACE2 and which ACE2 derived signaling pathways could be also involved via using a mouse model with lung injury induced by cigarette smoke (CS) exposure for 1 to 3 weeks. Wild-type (WT; C57BL/6) and ACE2 KO mice (ACE2(-/-)) were utilized to study CS-induced lung injury. Increases in the resting respiratory rate (RRR), pulmonary immunokines, leukocyte infiltration and bronchial hyperplasia were observed in the CS-exposed mice. Compared to WT mice, more serious physiopathological changes were found in ACE2(-/-) mice in the first week of CS exposure. CS exposure increased pulmonary ACE and ACE2 activities in WT mice, and significantly increased ACE in ACE2(-/-) mice. Furthermore, the activity of pulmonary MMPs was decreased in CS-exposed WT mice, whereas this activity was increased in ACE2(-/-) mice. CS exposure increased the pulmonary p-p38, p-JNK and p-ERK1/2 level in all mice. In ACE2(-/-) mice, a significant increase p-STAT3 signaling was detected; however, no effect was observed on the p-STAT3 level in WT mice. Our results support the hypothesis that ACE2 deficiency influences MMPs activation and STAT3 phosphorylation signaling to promote more pulmonary inflammation in the development of lung injury.

  7. Characterization and significance of ACE2 and Mas receptor in human colon adenocarcinoma.

    PubMed

    Bernardi, Stella; Zennaro, Cristina; Palmisano, Silvia; Velkoska, Elena; Sabato, Nicoletta; Toffoli, Barbara; Giacomel, Greta; Buri, Luigi; Zanconati, Fabrizio; Bellini, Giuseppe; Burrell, Louise M; De Manzini, Nicolò; Fabris, Bruno

    2012-03-01

    A new arm of the renin-angiotensin system (RAS) has been recently characterized; this includes angiotensin converting enzyme (ACE)2 and angiotensin (Ang)1-7, a heptapeptide acting through the Mas receptor (MasR). Recent studies show that Ang1-7 has an antiproliferative action on lung adenocarcinoma cells. The aim of this study was to characterize RAS expression in human colon adenocarcinoma and to investigate whether Ang1-7 exerts an antiproliferative effect on human colon adenocarcinoma cells. Gene, protein expression and enzymatic activity of the main components of the RAS were determined on non-neoplastic colon mucosa as well as on the tumor mass and the mucosa taken 5 cm distant from it, both collected from patients with colon adenocarcinoma. Two different human colon cancer cell lines were treated with AngII and Ang1-7. The novel finding of this study was that MasR was significantly upregulated in colon adenocarcinoma compared with non-neoplastic colon mucosa, which showed little or no expression of it. ACE gene expression and enzymatic activity were also increased in the tumors. However, AngII and Ang1-7 did not have any pro-/antiproliferative effects in the cell lines studied. The data suggest that upregulation of the MasR could be used as a diagnostic marker of colon adenocarcinoma.

  8. ACE2 is augmented in dystrophic skeletal muscle and plays a role in decreasing associated fibrosis.

    PubMed

    Riquelme, Cecilia; Acuña, María José; Torrejón, Javiera; Rebolledo, Daniela; Cabrera, Daniel; Santos, Robson A; Brandan, Enrique

    2014-01-01

    Duchenne muscular dystrophy (DMD) is the most common inherited neuromuscular disease and is characterized by absence of the cytoskeletal protein dystrophin, muscle wasting, and fibrosis. We previously demonstrated that systemic infusion or oral administration of angiotensin-(1-7) (Ang-(1-7)), a peptide with opposing effects to angiotensin II, normalized skeletal muscle architecture, decreased local fibrosis, and improved muscle function in mdx mice, a dystrophic model for DMD. In this study, we investigated the presence, activity, and localization of ACE2, the enzyme responsible for Ang-(1-7) production, in wild type (wt) and mdx skeletal muscle and in a model of induced chronic damage in wt mice. All dystrophic muscles studied showed higher ACE2 activity than wt muscle. Immunolocalization studies indicated that ACE2 was localized mainly at the sarcolemma and, to a lesser extent, associated with interstitial cells. Similar results were observed in the model of chronic damage in the tibialis anterior (TA) muscle. Furthermore, we evaluated the effect of ACE2 overexpression in mdx TA muscle using an adenovirus containing human ACE2 sequence and showed that expression of ACE2 reduced the fibrosis associated with TA dystrophic muscles. Moreover, we observed fewer inflammatory cells infiltrating the mdx muscle. Finally, mdx gastrocnemius muscles from mice infused with Ang-(1-7), which decreases fibrosis, contain less ACE2 associated with the muscle. This is the first evidence supporting ACE2 as an important therapeutic target to improve the dystrophic skeletal muscle phenotype.

  9. ACE expression in monocytes is induced by cytokines, phorbol ester and steroid

    SciTech Connect

    Lazarus, D.; Lanzillo, J.; Fanburg, B. )

    1991-03-15

    Angiotensin converting enzyme (ACE) levels are elevated in the serum and peripheral blood monocytes (PBM) of patients with granulomatous diseases. However, the role of ACE in (Mo) physiology and the regulation of the inflammatory response is not well understood. Since Mo can be stimulated to form giant cells using phorbol esters, glucocorticoids or certain inflammatory cytokines, the authors examined production of ACE protein by normal PBM, a Mo-like cell line, THP-1, and a macrophage-like cell line, U937 following stimulation with these agents. Using a sensitive ELISA assay, they found that in U937 cells, expression of ACE protein increased by 3.4 fold with dexamethasone, 3.7. fold with phorbol 12-myristate acetate (PMA), and 5.8 fold with the two agents combined. The cytokines IL-4 and GM-CSF substantially increased ACE expression, by 7.6 and 7.7 fold respectively, with maximal effect at 0.01 U/ml, while IFN-{gamma} and TNF-{alpha} had little effect. Similar results were found with PBM and THP-1 cells. The combination of dexamethasone and PMA also induced homotypic cluster formation in PBM, suggesting a correlation between cell adhesion and ACE production. The authors conclude that ACE expression in monocytes and macrophages is stimulated by low concentration of glucocorticoids and certain inflammatory cytokines. ACE may participate in the initiation and propagation of granulomatous inflammatory processes.

  10. Switch between life history strategies due to changes in glycolytic enzyme gene dosage in Saccharomyces cerevisiae.

    PubMed

    Wang, Shaoxiao; Spor, Aymé; Nidelet, Thibault; Montalent, Pierre; Dillmann, Christine; de Vienne, Dominique; Sicard, Delphine

    2011-01-01

    Adaptation is the process whereby a population or species becomes better fitted to its habitat through modifications of various life history traits which can be positively or negatively correlated. The molecular factors underlying these covariations remain to be elucidated. Using Saccharomyces cerevisiae as a model system, we have investigated the effects on life history traits of varying the dosage of genes involved in the transformation of resources into energy. Changing gene dosage for each of three glycolytic enzyme genes (hexokinase 2, phosphoglucose isomerase, and fructose-1,6-bisphosphate aldolase) resulted in variation in enzyme activities, glucose consumption rate, and life history traits (growth rate, carrying capacity, and cell size). However, the range of effects depended on which enzyme was expressed differently. Most interestingly, these changes revealed a genetic trade-off between carrying capacity and cell size, supporting the discovery of two extreme life history strategies already described in yeast populations: the "ants," which have lower glycolytic gene dosage, take up glucose slowly, and have a small cell size but reach a high carrying capacity, and the "grasshoppers," which have higher glycolytic gene dosage, consume glucose more rapidly, and allocate it to a larger cell size but reach a lower carrying capacity. These results demonstrate antagonist pleiotropy for glycolytic genes and show that altered dosage of a single gene drives a switch between two life history strategies in yeast.

  11. The four aldehyde oxidases of Drosophila melanogaster have different gene expression patterns and enzyme substrate specificities.

    PubMed

    Marelja, Zvonimir; Dambowsky, Miriam; Bolis, Marco; Georgiou, Marina L; Garattini, Enrico; Missirlis, Fanis; Leimkühler, Silke

    2014-06-15

    In the genome of Drosophila melanogaster, four genes coding for aldehyde oxidases (AOX1-4) were identified on chromosome 3. Phylogenetic analysis showed that the AOX gene cluster evolved via independent duplication events in the vertebrate and invertebrate lineages. The functional role and the substrate specificity of the distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles in this gene region, low pyridoxal oxidase (Po(lpo)) and aldehyde oxidase-1 (Aldox-1(n1)) are associated with a phenotype characterized by undetectable AOX enzymatic activity. However, the genes involved and the corresponding mutations have not yet been identified. In this study we characterized the activities, substrate specificities and expression profiles of the four AOX enzymes in D. melanogaster. We show that the Po(lpo)-associated phenotype is the consequence of a structural alteration of the AOX1 gene. We identified an 11-bp deletion in the Po(lpo) allele, resulting in a frame-shift event, which removes the molybdenum cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is detectable only during metamorphosis and characterize a Minos-AOX2 insertion in this developmental gene that disrupts its activity. We demonstrate that the Aldox-1(n1) phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our assays.

  12. The four aldehyde oxidases of Drosophila melanogaster have different gene expression patterns and enzyme substrate specificities

    PubMed Central

    Marelja, Zvonimir; Dambowsky, Miriam; Bolis, Marco; Georgiou, Marina L.; Garattini, Enrico; Missirlis, Fanis; Leimkühler, Silke

    2014-01-01

    In the genome of Drosophila melanogaster, four genes coding for aldehyde oxidases (AOX1–4) were identified on chromosome 3. Phylogenetic analysis showed that the AOX gene cluster evolved via independent duplication events in the vertebrate and invertebrate lineages. The functional role and the substrate specificity of the distinct Drosophila AOX enzymes is unknown. Two loss-of-function mutant alleles in this gene region, low pyridoxal oxidase (Polpo) and aldehyde oxidase-1 (Aldox-1n1) are associated with a phenotype characterized by undetectable AOX enzymatic activity. However, the genes involved and the corresponding mutations have not yet been identified. In this study we characterized the activities, substrate specificities and expression profiles of the four AOX enzymes in D. melanogaster. We show that the Polpo-associated phenotype is the consequence of a structural alteration of the AOX1 gene. We identified an 11-bp deletion in the Polpo allele, resulting in a frame-shift event, which removes the molybdenum cofactor domain of the encoded enzyme. Furthermore, we show that AOX2 activity is detectable only during metamorphosis and characterize a Minos-AOX2 insertion in this developmental gene that disrupts its activity. We demonstrate that the Aldox-1n1 phenotype maps to the AOX3 gene and AOX4 activity is not detectable in our assays. PMID:24737760

  13. Microbial regulation of the soil carbon cycle: evidence from gene-enzyme relationships.

    PubMed

    Trivedi, Pankaj; Delgado-Baquerizo, Manuel; Trivedi, Chanda; Hu, Hangwei; Anderson, Ian C; Jeffries, Thomas C; Zhou, Jizhong; Singh, Brajesh K

    2016-11-01

    A lack of empirical evidence for the microbial regulation of ecosystem processes, including carbon (C) degradation, hinders our ability to develop a framework to directly incorporate the genetic composition of microbial communities in the enzyme-driven Earth system models. Herein we evaluated the linkage between microbial functional genes and extracellular enzyme activity in soil samples collected across three geographical regions of Australia. We found a strong relationship between different functional genes and their corresponding enzyme activities. This relationship was maintained after considering microbial community structure, total C and soil pH using structural equation modelling. Results showed that the variations in the activity of enzymes involved in C degradation were predicted by the functional gene abundance of the soil microbial community (R(2)>0.90 in all cases). Our findings provide a strong framework for improved predictions on soil C dynamics that could be achieved by adopting a gene-centric approach incorporating the abundance of functional genes into process models.

  14. Identification and Molecular Characterization of Genes Coding Pharmaceutically Important Enzymes from Halo-Thermo Tolerant Bacillus.

    PubMed

    Safary, Azam; Moniri, Rezvan; Hamzeh-Mivehroud, Maryam; Dastmalchi, Siavoush

    2016-12-01

    Purpose: Robust pharmaceutical and industrial enzymes from extremophile microorganisms are main source of enzymes with tremendous stability under harsh conditions which make them potential tools for commercial and biotechnological applications. Methods: The genome of a Gram-positive halo-thermotolerant Bacillus sp. SL1, new isolate from Saline Lake, was investigated for the presence of genes coding for potentially pharmaceutical enzymes. We determined gene sequences for the enzymes laccase (CotA), l-asparaginase (ansA3, ansA1), glutamate-specific endopeptidase (blaSE), l-arabinose isomerase (araA2), endo-1,4-β mannosidase (gmuG), glutaminase (glsA), pectate lyase (pelA), cellulase (bglC1), aldehyde dehydrogenase (ycbD) and allantoinases (pucH) in the genome of Bacillus sp. SL1. Results: Based on the DNA sequence alignment results, six of the studied enzymes of Bacillus sp. SL-1 showed 100% similarity at the nucl