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1

Mitochondrial biogenesis: pharmacological approaches.  

PubMed

Organelle biogenesis is concomitant to organelle inheritance during cell division. It is necessary that organelles double their size and divide to give rise to two identical daughter cells. Mitochondrial biogenesis occurs by growth and division of pre-existing organelles and is temporally coordinated with cell cycle events [1]. However, mitochondrial biogenesis is not only produced in association with cell division. It can be produced in response to an oxidative stimulus, to an increase in the energy requirements of the cells, to exercise training, to electrical stimulation, to hormones, during development, in certain mitochondrial diseases, etc. [2]. Mitochondrial biogenesis is therefore defined as the process via which cells increase their individual mitochondrial mass [3]. Recent discoveries have raised attention to mitochondrial biogenesis as a potential target to treat diseases which up to date do not have an efficient cure. Mitochondria, as the major ROS producer and the major antioxidant producer exert a crucial role within the cell mediating processes such as apoptosis, detoxification, Ca2+ buffering, etc. This pivotal role makes mitochondria a potential target to treat a great variety of diseases. Mitochondrial biogenesis can be pharmacologically manipulated. This issue tries to cover a number of approaches to treat several diseases through triggering mitochondrial biogenesis. It contains recent discoveries in this novel field, focusing on advanced mitochondrial therapies to chronic and degenerative diseases, mitochondrial diseases, lifespan extension, mitohormesis, intracellular signaling, new pharmacological targets and natural therapies. It contributes to the field by covering and gathering the scarcely reported pharmacological approaches in the novel and promising field of mitochondrial biogenesis. There are several diseases that have a mitochondrial origin such as chronic progressive external ophthalmoplegia (CPEO) and the Kearns- Sayre syndrome (KSS), myoclonic epilepsy with ragged-red fibers (MERRF), mitochondrial encephalomyopathy, lactic acidosis and strokelike episodes (MELAS), Leber's hereditary optic neuropathy (LHON), the syndrome of neurogenic muscle weakness, ataxia and retinitis pigmentosa (NARP), and Leigh's syndrome. Likewise, other diseases in which mitochondrial dysfunction plays a very important role include neurodegenerative diseases, diabetes or cancer. Generally, in mitochondrial diseases a mutation in the mitochondrial DNA leads to a loss of functionality of the OXPHOS system and thus to a depletion of ATP and overproduction of ROS, which can, in turn, induce further mtDNA mutations. The work by Yu-Ting Wu, Shi-Bei Wu, and Yau-Huei Wei (Department of Biochemistry and Molecular Biology, National Yang-Ming University, Taiwan) [4] focuses on the aforementioned mitochondrial diseases with special attention to the compensatory mechanisms that prompt mitochondria to produce more energy even under mitochondrial defect-conditions. These compensatory mechanisms include the overexpression of antioxidant enzymes, mitochondrial biogenesis and overexpression of respiratory complex subunits, as well as metabolic shift to glycolysis. The pathways observed to be related to mitochondrial biogenesis as a compensatory adaptation to the energetic deficits in mitochondrial diseases are described (PGC- 1, Sirtuins, AMPK). Several pharmacological strategies to trigger these signaling cascades, according to these authors, are the use of bezafibrate to activate the PPAR-PGC-1? axis, the activation of AMPK by resveratrol and the use of Sirt1 agonists such as quercetin or resveratrol. Other strategies currently used include the addition of antioxidant supplements to the diet (dietary supplementation with antioxidants) such as L-carnitine, coenzyme Q10,MitoQ10 and other mitochondria-targeted antioxidants,N-acetylcysteine (NAC), vitamin C, vitamin E vitamin K1, vitamin B, sodium pyruvate or -lipoic acid. As aforementioned, other diseases do not have exclusively a mitochondrial origin but they might have an importan

Valero, Teresa

2014-01-01

2

Mitochondrial nutrients stimulate performance and mitochondrial biogenesis in exhaustively exercised rats.  

PubMed

The aim of this study was to investigate the effects of a combination of nutrients on physical performance, oxidative stress and mitochondrial biogenesis in rats subjected to exhaustive exercise. Rats were divided into sedentary control (SC), exhaustive exercise (EC) and exhaustive exercise with nutrient supplementation (EN). The nutrients include (mg/kg/day): R-?-lipoic acid 50, acetyl-L-carnitine 100, biotin 0.1, nicotinamide 15, riboflavin 6, pyridoxine 6, creatine 50, CoQ10 5, resveratrol 5 and taurine 100. Examination of running distances over the 4-week period revealed that EN rats ran significantly longer throughout the entire duration of the exhaustive exercise period compared with the EC rats. Nutrient supplementation significantly inhibited the increase in activities of alanine transaminase, lactate dehydrogenase and creatine kinase, reversed increases in malondialdehyde, inhibited decreases in glutathione S-transferase and total antioxidant capacity in plasma, and suppressed the elevation of reactive oxygen species and apoptosis in splenic lymphocytes. Nutrient supplementation increased the protein expression of mitochondrial complexes I, II and III, mtDNA number and transcription factors involved in mitochondrial biogenesis and fusion in skeletal muscle. These findings suggest that mitochondrial nutrient supplementation can reduce exhaustive exercise-induced oxidative damage and mitochondrial dysfunction, thus leading to enhancement of physical performance and of fatigue recovery. PMID:21507065

Sun, M; Qian, F; Shen, W; Tian, C; Hao, J; Sun, L; Liu, J

2012-12-01

3

Mitochondrial Biogenesis and Function in Arabidopsis†  

PubMed Central

Mitochondria represent the powerhouse of cells through their synthesis of ATP. However, understanding the role of mitochondria in the growth and development of plants will rely on a much deeper appreciation of the complexity of this organelle. Arabidopsis research has provided clear identification of mitochondrial components, allowed wide-scale analysis of gene expression, and has aided reverse genetic manipulation to test the impact of mitochondrial component loss on plant function. Forward genetics in Arabidopsis has identified mitochondrial involvement in mutations with notable impacts on plant metabolism, growth and development. Here we consider the evidence for components involved in mitochondria biogenesis, metabolism and signalling to the nucleus. PMID:22303236

Millar, A. Harvey; Small, Ian D.; Day, David A.; Whelan, James

2008-01-01

4

Regulation of mitochondrial biogenesis by thyroid hormone.  

PubMed

Thyroid hormone (T3) has a profound effect on mitochondrial biogenesis. T3-regulated gene expression is mediated by thyroid hormone receptor (TR) binding to thyroid hormone response elements (TREs). In concert with the action of various coactivators and corepressors this interaction leads to a modulation of the chromatin structure and subsequently to a modulation of gene expression of adjacent target genes. However, as numerous genes are endogenously regulated by T3, and a TRE appears to be absent in their regulatory elements, a TR-independent pathway of T3-mediated gene regulation is likely. In this review, we discuss the direct mechanisms of TR-dependent regulation of gene expression on the nuclear and mitochondrial genome by T3. We also summarise recent observations on an indirect mechanism of T3 action via intermediate factor(s). We discuss the regulation of nuclear respiratory factor 1 (NRF-1) and peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1alpha) by T3, suggesting NRF-1 and PGC-1alpha as attractive candidates for an intermediate factor of T3 action in vivo. PMID:12552316

Weitzel, Joachim M; Iwen, K Alexander H; Seitz, Hans J

2003-01-01

5

Regulation of Mitochondrial Biogenesis and Its Intersection with Inflammatory Responses  

PubMed Central

Abstract Significance: Mitochondria play a vital role in cellular homeostasis and are susceptible to damage from inflammatory mediators released by the host defense. Cellular recovery depends, in part, on mitochondrial quality control programs, including mitochondrial biogenesis. Recent Advances: Early-phase inflammatory mediator proteins interact with PRRs to activate NF-?B-, MAPK-, and PKB/Akt-dependent pathways, resulting in increased expression or activity of coactivators and transcription factors (e.g., PGC-1?, NRF-1, NRF-2, and Nfe2l2) that regulate mitochondrial biogenesis. Inflammatory upregulation of NOS2-induced NO causes mitochondrial dysfunction, but NO is also a signaling molecule upregulating mitochondrial biogenesis via PGC-1?, participating in Nfe2l2-mediated antioxidant gene expression and modulating inflammation. NO and reactive oxygen species generated by the host inflammatory response induce the redox-sensitive HO-1/CO system, causing simultaneous induction of mitochondrial biogenesis and antioxidant gene expression. Critical Issues: Recent evidence suggests that mitochondrial biogenesis and mitophagy are coupled through redox pathways; for instance, parkin, which regulates mitophagy in chronic inflammation, may also modulate mitochondrial biogenesis and is upregulated through NF-?B. Further research on parkin in acute inflammation is ongoing. This highlights certain common features of the host response to acute and chronic inflammation, but caution is warranted in extrapolating findings across inflammatory conditions. Future Directions: Inflammatory mitochondrial dysfunction and oxidative stress initiate further inflammatory responses through DAMP/PRR interactions and by inflammasome activation, stimulating mitophagy. A deeper understanding of mitochondrial quality control programs' impact on intracellular inflammatory signaling will improve our approach to the restoration of mitochondrial homeostasis in the resolution of acute inflammation. Antioxid. Redox Signal. 22, 965–976. PMID:25556935

Piantadosi, Claude A.

2015-01-01

6

Hyperglycemia decreases mitochondrial function: The regulatory role of mitochondrial biogenesis  

SciTech Connect

Increased generation of reactive oxygen species (ROS) is implicated in 'glucose toxicity' in diabetes. However, little is known about the action of glucose on the expression of transcription factors in hepatocytes, especially those involved in mitochondrial DNA (mtDNA) replication and transcription. Since mitochondrial functional capacity is dynamically regulated, we hypothesized that stressful conditions of hyperglycemia induce adaptations in the transcriptional control of cellular energy metabolism, including inhibition of mitochondrial biogenesis and oxidative metabolism. Cell viability, mitochondrial respiration, ROS generation and oxidized proteins were determined in HepG2 cells cultured in the presence of either 5.5 mM (control) or 30 mM glucose (high glucose) for 48 h, 96 h and 7 days. Additionally, mtDNA abundance, plasminogen activator inhibitor-1 (PAI-1), mitochondrial transcription factor A (TFAM) and nuclear respiratory factor-1 (NRF-1) transcripts were evaluated by real time PCR. High glucose induced a progressive increase in ROS generation and accumulation of oxidized proteins, with no changes in cell viability. Increased expression of PAI-1 was observed as early as 96 h of exposure to high glucose. After 7 days in hyperglycemia, HepG2 cells exhibited inhibited uncoupled respiration and decreased MitoTracker Red fluorescence associated with a 25% decrease in mtDNA and 16% decrease in TFAM transcripts. These results indicate that glucose may regulate mtDNA copy number by modulating the transcriptional activity of TFAM in response to hyperglycemia-induced ROS production. The decrease of mtDNA content and inhibition of mitochondrial function may be pathogenic hallmarks in the altered metabolic status associated with diabetes.

Palmeira, Carlos M. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal)], E-mail: palmeira@ci.uc.pt; Rolo, Anabela P. [Center for Neurosciences and Cell Biology of Coimbra, Department of Zoology, University of Coimbra, 3004-517 Coimbra (Portugal); Berthiaume, Jessica; Bjork, James A.; Wallace, Kendall B. [Department of Biochemistry and Molecular Biology, University of Minnesota School of Medicine, Duluth, MN (United States)

2007-12-01

7

Coordination of mitochondrial biogenesis by thyroid hormone.  

PubMed

Thyroid hormone (TH) has profound influence on metabolism that is closely linked to its effect on mitochondrial biogenesis and function. After a single injection of TH into mammals, physiological alterations (e.g. changes in oxygen consumption rates) are detectable after a lag period of ?48h. This characteristic lag period is somewhat surprising since non-genomic responses are already detectable within minutes, and first genomic responses within some hours after administration of TH. This review provides a model to explain the characteristic lag period: TH regulates a first series of TH target genes via classical activation of gene expression by binding to thyroid hormone response elements. Some directly regulated target genes serve as intermediate factors and subsequently regulate a second series of indirect TH target genes. Intermediate factors are transcription factors (such as NRF-1, NRF-2 and PPAR?) and transcriptional coactivators (such as PGC-1? and PGC-1?). In concert with several post-translational modifications, these intermediate factors orchestrate the physiological response to thyroid hormone in vivo. PMID:21664416

Weitzel, Joachim M; Iwen, K Alexander

2011-08-01

8

Mitochondrial biogenesis-associated factors underlie the magnitude of response to aerobic endurance training in rats.  

PubMed

Trainability is important in elite sport and in recreational physical activity, and the wide range for response to training is largely dependent on genotype. In this study, we compare a newly developed rat model system selectively bred for low and high gain in running distance from aerobic training to test whether genetic segregation for trainability associates with differences in factors associated with mitochondrial biogenesis. Low response trainer (LRT) and high response trainer (HRT) rats from generation 11 of artificial selection were trained five times a week, 30 min per day for 3 months at 70 % VO2max to study the mitochondrial molecular background of trainability. As expected, we found significant differential for the gain in running distance between LRT and HRT groups as a result of training. However, the changes in VO2max, COX-4, redox homeostasis associated markers (reactive oxygen species (ROS)), silent mating-type information regulation 2 homolog (SIRT1), NAD(+)/NADH ratio, proteasome (R2 subunit), and mitochondrial network related proteins such as mitochondrial fission protein 1 (Fis1) and mitochondrial fusion protein (Mfn1) suggest that these markers are not strongly involved in the differences in trainability between LRT and HRT. On the other hand, according to our results, we discovered that differences in basal activity of AMP-activated protein kinase alpha (AMPK?) and differential changes in aerobic exercise-induced responses of citrate synthase, carbonylated protein, peroxisome proliferator-activated receptor gamma coactivator-1? (PGC1-?), nuclear respiratory factor 1 (NRF1), mitochondrial transcription factor A (TFAM), and Lon protease limit trainability between these selected lines. From this, we conclude that mitochondrial biogenesis-associated factors adapt differently to aerobic exercise training in training sensitive and training resistant rats. PMID:24943897

Marton, Orsolya; Koltai, Erika; Takeda, Masaki; Koch, Lauren Gerard; Britton, Steven L; Davies, Kelvin J A; Boldogh, Istvan; Radak, Zsolt

2015-04-01

9

Molecular Genetics of Mitochondrial Biogenesis in Maize.  

Technology Transfer Automated Retrieval System (TEKTRAN)

The mitochondrial genome encodes proteins essential for mitochondrial respiration and ATP synthesis. Nuclear gene products, however, are required for the expression of mitochondrial genes and the elaboration of functional mitochondrial protein complexes. We are exploiting a unique collection of maiz...

10

After the banquet: mitochondrial biogenesis, mitophagy, and cell survival.  

PubMed

Mitochondria are highly dynamic organelles of crucial importance to the proper functioning of neuronal, cardiac and other cell types dependent upon aerobic efficiency. Mitochondrial dysfunction has been implicated in numerous human conditions, to include cancer, metabolic diseases, neurodegeneration, diabetes, and aging. In recent years, mitochondrial turnover by macroautophagy (mitophagy) has captured the limelight, due in part to discoveries that genes linked to Parkinson disease regulate this quality control process. A rapidly growing literature is clarifying effector mechanisms that underlie the process of mitophagy; however, factors that regulate positive or negative cellular outcomes have been less studied. Here, we review the literature on two major pathways that together may determine cellular adaptation vs. cell death in response to mitochondrial dysfunction. Mitochondrial biogenesis and mitophagy represent two opposing, but coordinated processes that determine mitochondrial content, structure, and function. Recent data indicate that the capacity to undergo mitochondrial biogenesis, which is dysregulated in disease states, may play a key role in determining cell survival following mitophagy-inducing injuries. The current literature on major pathways that regulate mitophagy and mitochondrial biogenesis is summarized, and mechanisms by which the interplay of these two processes may determine cell fate are discussed. We conclude that in primary neurons and other mitochondrially dependent cells, disruptions in any phase of the mitochondrial recycling process can contribute to cellular dysfunction and disease. Given the emerging importance of crosstalk among regulators of mitochondrial function, autophagy, and biogenesis, signaling pathways that coordinate these processes may contribute to therapeutic strategies that target or regulate mitochondrial turnover and regeneration. PMID:23787782

Zhu, Jianhui; Wang, Kent Z Q; Chu, Charleen T

2013-11-01

11

Echinochrome A Increases Mitochondrial Mass and Function by Modulating Mitochondrial Biogenesis Regulatory Genes  

PubMed Central

Echinochrome A (Ech A) is a natural pigment from sea urchins that has been reported to have antioxidant properties and a cardio protective effect against ischemia reperfusion injury. In this study, we ascertained whether Ech A enhances the mitochondrial biogenesis and oxidative phosphorylation in rat cardio myoblast H9c2 cells. To study the effects of Ech A on mitochondrial biogenesis, we measured mitochondrial mass, level of oxidative phosphorylation, and mitochondrial biogenesis regulatory gene expression. Ech A treatment did not induce cytotoxicity. However, Ech A treatment enhanced oxygen consumption rate and mitochondrial ATP level. Likewise, Ech A treatment increased mitochondrial contents in H9c2 cells. Furthermore, Ech A treatment up-regulated biogenesis of regulatory transcription genes, including proliferator-activated receptor gamma co-activator (PGC)-1?, estrogen-related receptor (ERR)-?, peroxisome proliferator-activator receptor (PPAR)-?, and nuclear respiratory factor (NRF)-1 and such mitochondrial transcription regulatory genes as mitochondrial transcriptional factor A (TFAM), mitochondrial transcription factor B2 (TFB2M), mitochondrial DNA direct polymerase (POLMRT), single strand binding protein (SSBP) and Tu translation elongation factor (TUFM). In conclusion, these data suggest that Ech A is a potentiated marine drug which enhances mitochondrial biogenesis. PMID:25196935

Jeong, Seung Hun; Kim, Hyoung Kyu; Song, In-Sung; Noh, Su Jin; Marquez, Jubert; Ko, Kyung Soo; Rhee, Byoung Doo; Kim, Nari; Mishchenko, Natalia P.; Fedoreyev, Sergey A.; Stonik, Valentin A.; Han, Jin

2014-01-01

12

Exercise-induced heart mitochondrial cholesterol depletion influences the inhibition of mitochondrial swelling.  

PubMed

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-?-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-?-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise. PMID:23733522

Ziolkowski, Wieslaw; Vadhana M S, Dhivya; Kaczor, Jan Jacek; Olek, Robert Antoni; Flis, Damian Jozef; Halon, Malgorzata; Wozniak, Michal; Fedeli, Donatella; Carloni, Manuel; Antosiewicz, Jedrzej; Gabbianelli, Rosita

2013-10-01

13

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis  

E-print Network

Ssq1, a Mitochondrial Hsp70 Involved in Iron-Sulfur (Fe/S) Center Biogenesis SIMILARITIES function together to assist in the biogenesis of iron- sulfur (Fe/S) centers in the mitochondrial matrix chaperones work to- gether, along with other proteins, in the processes of iron- sulfur center biogenesis

Craig, Elizabeth A

14

Increases in mitochondrial biogenesis impair carcinogenesis at multiple levels.  

PubMed

Although mitochondrial respiration is decreased in most cancer cells, the role of this decrease in carcinogenesis and cancer progression is still unclear. To better understand this phenomenon, instead of further inhibiting mitochondrial function, we induced mitochondrial biogenesis in transformed cells by activating the peroxisome proliferator-activated receptors (PPARs)/peroxisome proliferator-activated receptor gamma co-activator 1? (PGC-1?) pathways. This was achieved by treating the cells with bezafibrate, a PPARs panagonist that also enhances PGC-1? expression. We confirmed that bezafibrate treatment led to increased mitochondrial proteins and enzyme functions. We found that cells with increased mitochondrial biogenesis had decreased growth rates in glucose-containing medium. In addition, they became less invasive, which was directly linked to the reduced lactate levels. Surprisingly, even though bezafibrate-treated cells had higher levels of mitochondrial markers, total respiration was not significantly altered. However, respiratory coupling, and ATP levels were. Our data show that by increasing the efficiency of the mitochondrial oxidative phosphorylation system, cancer progression is hampered by decreases in cell proliferation and invasiveness. PMID:21855427

Wang, Xiao; Moraes, Carlos T

2011-10-01

15

Coordination of plant mitochondrial biogenesis: keeping pace with cellular requirements  

PubMed Central

Plant mitochondria are complex organelles that carry out numerous metabolic processes related with the generation of energy for cellular functions and the synthesis and degradation of several compounds. Mitochondria are semiautonomous and dynamic organelles changing in shape, number, and composition depending on tissue or developmental stage. The biogenesis of functional mitochondria requires the coordination of genes present both in the nucleus and the organelle. In addition, due to their central role, all processes held inside mitochondria must be finely coordinated with those in other organelles according to cellular demands. Coordination is achieved by transcriptional control of nuclear genes encoding mitochondrial proteins by specific transcription factors that recognize conserved elements in their promoter regions. In turn, the expression of most of these transcription factors is linked to developmental and environmental cues, according to the availability of nutrients, light–dark cycles, and warning signals generated in response to stress conditions. Among the signals impacting in the expression of nuclear genes, retrograde signals that originate inside mitochondria help to adjust mitochondrial biogenesis to organelle demands. Adding more complexity, several nuclear encoded proteins are dual localized to mitochondria and either chloroplasts or the nucleus. Dual targeting might establish a crosstalk between the nucleus and cell organelles to ensure a fine coordination of cellular activities. In this article, we discuss how the different levels of coordination of mitochondrial biogenesis interconnect to optimize the function of the organelle according to both internal and external demands. PMID:24409193

Welchen, Elina; García, Lucila; Mansilla, Natanael; Gonzalez, Daniel H.

2014-01-01

16

Hydroxytyrosol promotes mitochondrial biogenesis and mitochondrial function in 3T3-L1 adipocytes.  

PubMed

Hydroxytyrosol (HT) in extra-virgin olive oil is considered one of the most important polyphenolic compounds responsible for the health benefits of the Mediterranean diet for lowering incidence of cardiovascular disease, the most common and most serious complication of diabetes. We propose that HT may prevent these diseases by a stimulation of mitochondrial biogenesis that leads to enhancement of mitochondrial function and cellular defense systems. In the present study, we investigated effects of HT that stimulate mitochondrial biogenesis and promote mitochondrial function in 3T3-L1 adipocytes. HT over the concentration range of 0.1-10 micromol/L stimulated the promoter transcriptional activation and protein expression of peroxisome proliferator-activated receptor (PPAR) coactivator 1 alpha (PPARGC1 alpha, the central factor for mitochondrial biogenesis) and its downstream targets; these included nuclear respiration factors 1 and 2 and mitochondrial transcription factor A, which leads to an increase in mitochondrial DNA (mtDNA) and in the number of mitochondria. Knockdown of Ppargc1 alpha by siRNA blocked HT's stimulating effect on Complex I expression and mtDNA copy number. The HT treatment resulted in an enhancement of mitochondrial function, including an increase in activity and protein expression of Mitochondrial Complexes I, II, III and V; increased oxygen consumption; and a decrease in free fatty acid contents in the adipocytes. The mechanistic study of the PPARGC1 alpha activation signaling pathway demonstrated that HT is an activator of 5'AMP-activated protein kinase and also up-regulates gene expression of PPAR alpha, CPT-1 and PPAR gamma. These data suggest that HT is able to promote mitochondrial function by stimulating mitochondrial biogenesis. PMID:19576748

Hao, Jiejie; Shen, Weili; Yu, Guangli; Jia, Haiqun; Li, Xuesen; Feng, Zhihui; Wang, Ying; Weber, Peter; Wertz, Karin; Sharman, Edward; Liu, Jiankang

2010-07-01

17

Selenium preserves mitochondrial function, stimulates mitochondrial biogenesis, and reduces infarct volume after focal cerebral ischemia  

PubMed Central

Background Mitochondrial dysfunction is one of the major events responsible for activation of neuronal cell death pathways during cerebral ischemia. Trace element selenium has been shown to protect neurons in various diseases conditions. Present study is conducted to demonstrate that selenium preserves mitochondrial functional performance, activates mitochondrial biogenesis and prevents hypoxic/ischemic cell damage. Results The study conducted on HT22 cells exposed to glutamate or hypoxia and mice subjected to 60-min focal cerebral ischemia revealed that selenium (100 nM) pretreatment (24?h) significantly attenuated cell death induced by either glutamate toxicity or hypoxia. The protective effects were associated with reduction of glutamate and hypoxia-induced ROS production and alleviation of hypoxia-induced suppression of mitochondrial respiratory complex activities. The animal studies demonstrated that selenite pretreatment (0.2?mg/kg?i.p. once a day for 7?days) ameliorated cerebral infarct volume and reduced DNA oxidation. Furthermore, selenite increased protein levels of peroxisome proliferator-activated receptor-? coactivator 1alpha (PGC-1?) and nuclear respiratory factor 1 (NRF1), two key nuclear factors that regulate mitochondrial biogenesis. Finally, selenite normalized the ischemia-induced activation of Beclin 1 and microtubule-associated protein 1 light chain 3-II (LC3-II), markers for autophagy. Conclusions These results suggest that selenium protects neurons against hypoxic/ischemic damage by reducing oxidative stress, restoring mitochondrial functional activities and stimulating mitochondrial biogenesis. PMID:22776356

2012-01-01

18

Lipophilic antioxidants prevent lipopolysaccharide-induced mitochondrial dysfunction through mitochondrial biogenesis improvement.  

PubMed

Oxidative stress is implicated in several infectious diseases. In this regard, lipopolysaccharide (LPS), an endotoxic component, induces mitochondrial dysfunction and oxidative stress in several pathological events such as periodontal disease or sepsis. In our experiments, LPS-treated fibroblasts provoked increased oxidative stress, mitochondrial dysfunction, reduced oxygen consumption and mitochondrial biogenesis. After comparing coenzyme Q10 (CoQ10) and N-acetylcysteine (NAC), we observed a more significant protection of CoQ10 than of NAC, which was comparable with other lipophilic and hydrophilic antioxidants such as vitamin E or BHA respectively. CoQ10 improved mitochondrial biogenesis by activating PGC-1? and TFAM. This lipophilic antioxidant protection was observed in mice after LPS injection. These results show that mitochondria-targeted lipophilic antioxidants could be a possible specific therapeutic strategy in pharmacology in the treatment of infectious diseases and their complications. PMID:25447593

Bullón, Pedro; Román-Malo, Lourdes; Marín-Aguilar, Fabiola; Alvarez-Suarez, José Miguel; Giampieri, Francesca; Battino, Maurizio; Cordero, Mario D

2015-01-01

19

Cardiac mitochondrial biogenesis in endotoxemia is not accompanied by mitochondrial function recovery.  

PubMed

Mitochondrial biogenesis emerges as a compensatory mechanism involved in the recovery process in endotoxemia and sepsis. The aim of this work was to analyze the time course of the cardiac mitochondrial biogenesis process occurring during endotoxemia, with emphasis on the quantitative analysis of mitochondrial function. Female Sprague-Dawley rats (45 days old) were ip injected with LPS (10 mg/kg). Measurements were performed at 0-24 h after LPS administration. PGC-1? and mtTFA expression for biogenesis and p62 and LC3 expression for autophagy were analyzed by Western blot; mitochondrial DNA levels by qPCR, and mitochondrial morphology by transmission electron microscopy. Mitochondrial function was evaluated as oxygen consumption and respiratory chain complex activity. PGC-1? and mtTFA expression significantly increased in every time point analyzed, and mitochondrial mass was increased by 20% (P<0.05) at 24 h. p62 expression was significantly decreased in a time-dependent manner. LC3-II expression was significantly increased at all time points analyzed. Ultrastructurally, mitochondria displayed several abnormalities (internal vesicles, cristae disruption, and swelling) at 6 and 18 h. Structures compatible with fusion/fission processes were observed at 24 h. A significant decrease in state 3 respiration was observed in every time point analyzed (LPS 6h: 20%, P<0.05). Mitochondrial complex I activity was found decreased by 30% in LPS-treated animals at 6 and 24h. Complex II and complex IV showed decreased activity only at 24 h. The present results show that partial restoration of cardiac mitochondrial architecture is not accompanied by improvement of mitochondrial function in acute endotoxemia. The key implication of our study is that cardiac failure due to bioenergetic dysfunction will be overcome by therapeutic interventions aimed to restore cardiac mitochondrial function. PMID:25224040

Vanasco, Virginia; Saez, Trinidad; Magnani, Natalia D; Pereyra, Leonardo; Marchini, Timoteo; Corach, Alejandra; Vaccaro, María Inés; Corach, Daniel; Evelson, Pablo; Alvarez, Silvia

2014-12-01

20

Mitochondrial biogenesis in the pulmonary vasculature during inhalation lung injury and fibrosis  

EPA Science Inventory

Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammatio...

21

CLUH regulates mitochondrial biogenesis by binding mRNAs of nuclear-encoded mitochondrial proteins.  

PubMed

Mitochondrial function requires coordination of two genomes for protein biogenesis, efficient quality control mechanisms, and appropriate distribution of the organelles within the cell. How these mechanisms are integrated is currently not understood. Loss of the Clu1/CluA homologue (CLUH) gene led to clustering of the mitochondrial network by an unknown mechanism. We find that CLUH is coregulated both with genes encoding mitochondrial proteins and with genes involved in ribosomal biogenesis and translation. Our functional analysis identifies CLUH as a cytosolic messenger ribonucleic acid (RNA; mRNA)-binding protein. RNA immunoprecipitation experiments followed by next-generation sequencing demonstrated that CLUH specifically binds a subset of mRNAs encoding mitochondrial proteins. CLUH depletion decreased the levels of proteins translated by target transcripts and caused mitochondrial clustering. A fraction of CLUH colocalizes with tyrosinated tubulin and can be detected close to mitochondria, suggesting a role in regulating transport or translation of target transcripts close to mitochondria. Our data unravel a novel mechanism linking mitochondrial biogenesis and distribution. PMID:25349259

Gao, Jie; Schatton, Désirée; Martinelli, Paola; Hansen, Henriette; Pla-Martin, David; Barth, Esther; Becker, Christian; Altmueller, Janine; Frommolt, Peter; Sardiello, Marco; Rugarli, Elena I

2014-10-27

22

MTERF3 Regulates Mitochondrial Ribosome Biogenesis in Invertebrates and Mammals  

PubMed Central

Regulation of mitochondrial DNA (mtDNA) expression is critical for the control of oxidative phosphorylation in response to physiological demand, and this regulation is often impaired in disease and aging. We have previously shown that mitochondrial transcription termination factor 3 (MTERF3) is a key regulator that represses mtDNA transcription in the mouse, but its molecular mode of action has remained elusive. Based on the hypothesis that key regulatory mechanisms for mtDNA expression are conserved in metazoans, we analyzed Mterf3 knockout and knockdown flies. We demonstrate here that decreased expression of MTERF3 not only leads to activation of mtDNA transcription, but also impairs assembly of the large mitochondrial ribosomal subunit. This novel function of MTERF3 in mitochondrial ribosomal biogenesis is conserved in the mouse, thus we identify a novel and unexpected role for MTERF3 in coordinating the crosstalk between transcription and translation for the regulation of mammalian mtDNA gene expression. PMID:23300484

Metodiev, Metodi D.; Spåhr, Henrik; Mourier, Arnaud; Freyer, Christoph; Ruzzenente, Benedetta; Tain, Luke; Grönke, Sebastian; Baggio, Francesca; Kukat, Christian; Kremmer, Elisabeth; Wibom, Rolf; Polosa, Paola Loguercio; Habermann, Bianca; Partridge, Linda; Park, Chan Bae; Larsson, Nils-Göran

2013-01-01

23

The ?2-Adrenoceptor Agonist Formoterol Stimulates Mitochondrial Biogenesis  

PubMed Central

Mitochondrial dysfunction is a common mediator of disease and organ injury. Although recent studies show that inducing mitochondrial biogenesis (MB) stimulates cell repair and regeneration, only a limited number of chemicals are known to induce MB. To examine the impact of the ?-adrenoceptor (?-AR) signaling pathway on MB, primary renal proximal tubule cells (RPTC) and adult feline cardiomyocytes were exposed for 24 h to multiple ?-AR agonists: isoproterenol (nonselective ?-AR agonist), (±)-(R*,R*)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy] acetic acid sodium hydrate (BRL 37344) (selective ?3-AR agonist), and formoterol (selective ?2-AR agonist). The Seahorse Biosciences (North Billerica, MA) extracellular flux analyzer was used to quantify carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled oxygen consumption rate (OCR), a marker of maximal electron transport chain activity. Isoproterenol and BRL 37244 did not alter mitochondrial respiration at any of the concentrations examined. Formoterol exposure resulted in increases in both FCCP-uncoupled OCR and mitochondrial DNA (mtDNA) copy number. The effect of formoterol on OCR in RPTC was inhibited by the ?-AR antagonist propranolol and the ?2-AR inverse agonist 3-(isopropylamino)-1-[(7-methyl-4-indanyl)oxy]butan-2-ol hydrochloride (ICI-118,551). Mice exposed to formoterol for 24 or 72 h exhibited increases in kidney and heart mtDNA copy number, peroxisome proliferator-activated receptor ? coactivator 1?, and multiple genes involved in the mitochondrial electron transport chain (F0 subunit 6 of transmembrane F-type ATP synthase, NADH dehydrogenase subunit 1, NADH dehydrogenase subunit 6, and NADH dehydrogenase [ubiquinone] 1? subcomplex subunit 8). Cheminformatic modeling, virtual chemical library screening, and experimental validation identified nisoxetine from the Sigma Library of Pharmacologically Active Compounds and two compounds from the ChemBridge DIVERSet that increased mitochondrial respiratory capacity. These data provide compelling evidence for the use and development of ?2-AR ligands for therapeutic MB. PMID:22490378

Wills, Lauren P.; Trager, Richard E.; Beeson, Gyda C.; Lindsey, Christopher C.; Peterson, Yuri K.; Beeson, Craig C.

2012-01-01

24

Quercetin induces mitochondrial biogenesis through activation of HO-1 in HepG2 cells.  

PubMed

The regeneration of mitochondria by regulated biogenesis plays an important homeostatic role in cells and tissues and furthermore may provide an adaptive mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells. Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO-1/CO system. This study focused on the mechanism by which the natural antioxidant quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that quercetin treatment induced expression of mitochondrial biogenesis activators (PGC-1 ? , NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory effects of quercetin on mitochondrial biogenesis could be recapitulated in vivo in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti-inflammatory effect in the liver of mice treated with LPS and prevented impairment of mitochondrial biogenesis by LPS in vivo. These salutary effects of quercetin in vivo were also antagonized by SnPP. Thus, our results suggest that quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system in vitro and in vivo. The beneficial effects of quercetin may provide a therapeutic basis in inflammatory diseases and sepsis. PMID:24288584

Rayamajhi, Nabin; Kim, Seul-Ki; Go, Hiroe; Joe, Yeonsoo; Callaway, Zak; Kang, Jae-Gu; Ryter, Stefan W; Chung, Hun Taeg

2013-01-01

25

Quercetin Induces Mitochondrial Biogenesis through Activation of HO-1 in HepG2 Cells  

PubMed Central

The regeneration of mitochondria by regulated biogenesis plays an important homeostatic role in cells and tissues and furthermore may provide an adaptive mechanism in certain diseases such as sepsis. The heme oxygenase (HO-1)/carbon monoxide (CO) system is an inducible cytoprotective mechanism in mammalian cells. Natural antioxidants can provide therapeutic benefit, in part, by inducing the HO-1/CO system. This study focused on the mechanism by which the natural antioxidant quercetin can induce mitochondrial biogenesis in HepG2 cells. We found that quercetin treatment induced expression of mitochondrial biogenesis activators (PGC-1?, NRF-1, TFAM), mitochondrial DNA (mtDNA), and proteins (COX IV) in HepG2 cells. The HO inhibitor SnPP and the CO scavenger hemoglobin reversed the effects of quercetin on mitochondrial biogenesis in HepG2 cells. The stimulatory effects of quercetin on mitochondrial biogenesis could be recapitulated in vivo in liver tissue and antagonized by SnPP. Finally, quercetin conferred an anti-inflammatory effect in the liver of mice treated with LPS and prevented impairment of mitochondrial biogenesis by LPS in vivo. These salutary effects of quercetin in vivo were also antagonized by SnPP. Thus, our results suggest that quercetin enhances mitochondrial biogenesis mainly via the HO-1/CO system in vitro and in vivo. The beneficial effects of quercetin may provide a therapeutic basis in inflammatory diseases and sepsis. PMID:24288584

Rayamajhi, Nabin; Kim, Seul-Ki; Go, Hiroe; Joe, Yeonsoo; Callaway, Zak; Kang, Jae-Gu; Ryter, Stefan W.; Chung, Hun Taeg

2013-01-01

26

Sirt3 Protects Cortical Neurons against Oxidative Stress via Regulating Mitochondrial Ca2+ and Mitochondrial Biogenesis  

PubMed Central

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis. PMID:25196599

Dai, Shu-Hui; Chen, Tao; Wang, Yu-Hai; Zhu, Jie; Luo, Peng; Rao, Wei; Yang, Yue-Fan; Fei, Zhou; Jiang, Xiao-Fan

2014-01-01

27

Sirt3 protects cortical neurons against oxidative stress via regulating mitochondrial Ca2+ and mitochondrial biogenesis.  

PubMed

Oxidative stress is a well-established event in the pathology of several neurobiological diseases. Sirt3 is a nicotinamide adenine nucleotide (NAD+)-dependent protein deacetylase that regulates mitochondrial function and metabolism in response to caloric restriction and stress. This study aims to investigate the role of Sirt3 in H2O2 induced oxidative neuronal injury in primary cultured rat cortical neurons. We found that H2O2 treatment significantly increased the expression of Sirt3 in a time-dependent manner at both mRNA and protein levels. Knockdown of Sirt3 with a specific small interfering RNA (siRNA) exacerbated H2O2-induced neuronal injury, whereas overexpression of Sirt3 by lentivirus transfection inhibited H2O2-induced neuronal damage reduced the generation of reactive oxygen species (ROS), and increased the activities of endogenous antioxidant enzymes. In addition, the intra-mitochondrial Ca2+ overload, but not cytosolic Ca2+ increase after H2O2 treatment, was strongly attenuated after Sirt3 overexpression. Overexpression of Sirt3 also increased the content of mitochondrial DNA (mtDNA) and the expression of mitochondrial biogenesis related transcription factors. All these results suggest that Sirt3 acts as a prosurvival factor playing an essential role to protect cortical neurons under H2O2 induced oxidative stress, possibly through regulating mitochondrial Ca2+ homeostasis and mitochondrial biogenesis. PMID:25196599

Dai, Shu-Hui; Chen, Tao; Wang, Yu-Hai; Zhu, Jie; Luo, Peng; Rao, Wei; Yang, Yue-Fan; Fei, Zhou; Jiang, Xiao-Fan

2014-01-01

28

The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts  

SciTech Connect

The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans. -- Highlights: ? Cells respond to certain environmental toxins by increasing mitochondrial biogenesis. ? We investigated the effect of Chloramphenicol and EtBr in primary human fibroblasts. ? Inhibiting mitochondrial protein synthesis or DNA replication elicit different effects. ? We provide novel insights into the cellular responses toxins and antibiotics.

Kao, Li-Pin; Ovchinnikov, Dmitry; Wolvetang, Ernst, E-mail: e.wolvetang@uq.edu.au

2012-05-15

29

?2-adrenoceptor agonists in the regulation of mitochondrial biogenesis  

PubMed Central

The stimulation of mitochondrial biogenesis (MB) via cell surface G-protein coupled receptors is a promising strategy for cell repair and regeneration. Here we report the specificity and chemical rationale of a panel of ?2-adrenoceptor agonists with regards to MB. Using primary cultures of renal cells, a diverse panel of ?2-adrenoceptor agonists elicited three distinct phenotypes: full MB, partial MB, and non-MB. Full MB compounds had efficacy in the low nanomolar range and represent two chemical scaffolds containing three distinct chemical clusters. Interestingly, the MB phenotype did not correlate with reported receptor affinity or chemical similarity. Chemical clusters were then subjected to pharmacophore modeling creating two models with unique and distinct features, consisting of five conserved amongst full MB compounds were identified. The two discrete pharmacophore models were coalesced into a consensus pharmacophore with four unique features elucidating the spatial and chemical characteristics required to stimulate MB. PMID:23954364

Peterson, Yuri K.; Cameron, Robert B.; Wills, Lauren P.; Trager, Richard E.; Lindsey, Chris C.; Beeson, Craig C.; Schnellmann, Rick G.

2014-01-01

30

Exercise Increases Mitochondrial PGC-1? Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis*  

PubMed Central

Endurance exercise is known to induce metabolic adaptations in skeletal muscle via activation of the transcriptional co-activator peroxisome proliferator-activated receptor ? co-activator 1? (PGC-1?). PGC-1? regulates mitochondrial biogenesis via regulating transcription of nuclear-encoded mitochondrial genes. Recently, PGC-1? has been shown to reside in mitochondria; however, the physiological consequences of mitochondrial PGC-1? remain unknown. We sought to delineate if an acute bout of endurance exercise can mediate an increase in mitochondrial PGC-1? content where it may co-activate mitochondrial transcription factor A to promote mtDNA transcription. C57Bl/6J mice (n = 12/group; ? = ?) were randomly assigned to sedentary (SED), forced-endurance (END) exercise (15 m/min for 90 min), or forced endurance +3 h of recovery (END+3h) group. The END group was sacrificed immediately after exercise, whereas the SED and END+3h groups were euthanized 3 h after acute exercise. Acute exercise coordinately increased the mRNA expression of nuclear and mitochondrial DNA-encoded mitochondrial transcripts. Nuclear and mitochondrial abundance of PGC-1? in END and END+3h groups was significantly higher versus SED mice. In mitochondria, PGC-1? is in a complex with mitochondrial transcription factor A at mtDNA D-loop, and this interaction was positively modulated by exercise, similar to the increased binding of PGC-1? at the NRF-1 promoter. We conclude that in response to acute altered energy demands, PGC-1? re-localizes into nuclear and mitochondrial compartments where it functions as a transcriptional co-activator for both nuclear and mitochondrial DNA transcription factors. These results suggest that PGC-1? may dynamically facilitate nuclear-mitochondrial DNA cross-talk to promote net mitochondrial biogenesis. PMID:21245132

Safdar, Adeel; Little, Jonathan P.; Stokl, Andrew J.; Hettinga, Bart P.; Akhtar, Mahmood; Tarnopolsky, Mark A.

2011-01-01

31

Heat exposure does not alter eccentric exercise-induced increases in mitochondrial calcium and respiratory dysfunction  

Microsoft Academic Search

Eccentric exercise can lead to muscle damage including dramatic changes to mitochondrial calcium content (MCC) and impaired\\u000a respiratory function. Heat acclimation can create a cross-tolerance to a number of stresses including eccentric exercise but\\u000a little is known about any protection to mitochondria. We hypothesised that intermittent heat exposure will lead to improved\\u000a control of MCC and to preserved mitochondrial function

Ben Rattray; C. Caillaud; P. A. Ruell; M. W. Thompson

32

A high-throughput respirometric assay for mitochondrial biogenesis and toxicity.  

PubMed

Mitochondria are a common target of toxicity for drugs and other chemicals and result in decreased aerobic metabolism and cell death. In contrast, mitochondrial biogenesis restores cell vitality, and there is a need for new agents to induce biogenesis. Current cell-based models of mitochondrial biogenesis or toxicity are inadequate because cultured cell lines are highly glycolytic with minimal aerobic metabolism and altered mitochondrial physiology. In addition, there are no high-throughput real-time assays that assess mitochondrial function. We adapted primary cultures of renal proximal tubular cells (RPTCs) that exhibit in vivo levels of aerobic metabolism, are not glycolytic, and retain higher levels of differentiated functions and used the Seahorse Bioscience analyzer to measure mitochondrial function in real time in multiwell plates. Using uncoupled respiration as a marker of electron transport chain (ETC) integrity, the nephrotoxicants cisplatin, HgCl(2), and gentamicin exhibited mitochondrial toxicity prior to decreases in basal respiration and cell death. Conversely, using FCCP (carbonylcyanide p-trifluoromethoxyphenylhydrazone)-uncoupled respiration as a marker of maximal ETC activity, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), SRT1720, resveratrol, daidzein, and metformin produced mitochondrial biogenesis in RPTCs. The merger of the RPTC model and multiwell respirometry results in a single high-throughput assay to measure mitochondrial biogenesis and toxicity and nephrotoxic potential. PMID:20465991

Beeson, Craig C; Beeson, Gyda C; Schnellmann, Rick G

2010-09-01

33

Mitochondrial Rab GAPs govern autophagosome biogenesis during mitophagy  

PubMed Central

Damaged mitochondria can be selectively eliminated by mitophagy. Although two gene products mutated in Parkinson’s disease, PINK1, and Parkin have been found to play a central role in triggering mitophagy in mammals, how the pre-autophagosomal isolation membrane selectively and accurately engulfs damaged mitochondria remains unclear. In this study, we demonstrate that TBC1D15, a mitochondrial Rab GTPase-activating protein (Rab-GAP), governs autophagosome biogenesis and morphology downstream of Parkin activation. To constrain autophagosome morphogenesis to that of the cargo, TBC1D15 inhibits Rab7 activity and associates with both the mitochondria through binding Fis1 and the isolation membrane through the interactions with LC3/GABARAP family members. Another TBC family member TBC1D17, also participates in mitophagy and forms homodimers and heterodimers with TBC1D15. These results demonstrate that TBC1D15 and TBC1D17 mediate proper autophagic encapsulation of mitochondria by regulating Rab7 activity at the interface between mitochondria and isolation membranes. DOI: http://dx.doi.org/10.7554/eLife.01612.001 PMID:24569479

Yamano, Koji; Fogel, Adam I; Wang, Chunxin; van der Bliek, Alexander M; Youle, Richard J

2014-01-01

34

Evidences that maternal swimming exercise improves antioxidant defenses and induces mitochondrial biogenesis in the brain of young Wistar rats.  

PubMed

Physical exercise during pregnancy has been considered beneficial to mother and child. Recent studies showed that maternal swimming improves memory in the offspring, increases hippocampal neurogenesis and levels of neurotrophic factors. The objective of this work was to investigate the effect of maternal swimming during pregnancy on redox status and mitochondrial parameters in brain structures from the offspring. Adult female Wistar rats were submitted to five swimming sessions (30 min/day) prior to mating with adult male Wistar rats, and then trained during the pregnancy (five sessions of 30-min swimming/week). The litter was sacrificed when 7 days old, when cerebellum, parietal cortex, hippocampus, and striatum were dissected. We evaluated the production of reactive species and antioxidant status, measuring the activities of superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GPx), as well as non-enzymatic antioxidants. We also investigated a potential mitochondrial biogenesis regarding mitochondrion mass and membrane potential, through cytometric approaches. Our results showed that maternal swimming exercise promoted an increase in reactive species levels in cerebellum, parietal cortex, and hippocampus, demonstrated by an increase in dichlorofluorescein oxidation. Mitochondrial superoxide was reduced in cerebellum and parietal cortex, while nitrite levels were increased in cerebellum, parietal cortex, hippocampus, and striatum. Antioxidant status was improved in cerebellum, parietal cortex, and hippocampus. SOD activity was increased in parietal cortex, and was not altered in the remaining brain structures. CAT and GPx activities, as well as non-enzymatic antioxidant potential, were increased in cerebellum, parietal cortex, and hippocampus of rats whose mothers were exercised. Finally, we observed an increased mitochondrial mass and membrane potential, suggesting mitochondriogenesis, in cerebellum and parietal cortex of pups subjected to maternal swimming. In conclusion, maternal swimming exercise induced neurometabolic programing in the offspring that could be of benefit to the rats against future cerebral insults. PMID:23639877

Marcelino, T B; Longoni, A; Kudo, K Y; Stone, V; Rech, A; de Assis, A M; Scherer, E B S; da Cunha, M J; Wyse, A T S; Pettenuzzo, L F; Leipnitz, G; Matté, C

2013-08-29

35

Acute Exercise Induced Mitochondrial H2O2 Production in Mouse Skeletal Muscle: Association with p66Shc and FOXO3a Signaling and Antioxidant Enzymes  

PubMed Central

Exercise induced skeletal muscle phenotype change involves a complex interplay between signaling pathways and downstream regulators. This study aims to investigate the effect of acute exercise on mitochondrial H2O2 production and its association with p66Shc, FOXO3a, and antioxidant enzymes. Male ICR/CD-1 mice were subjected to an acute exercise. Muscle tissues (gastrocnemius and quadriceps femoris) were taken after exercise to measure mitochondrial H2O2 content, expression of p66Shc and FOXO3a, and the activity of antioxidant enzymes. The results showed that acute exercise significantly increased mitochondrial H2O2 content and expressions of p66Shc and FOXO3a in a time-dependent manner, with a linear correlation between the increase in H2O2 content and p66Shc or FOXO3a expression. The activity of mitochondrial catalase was slightly reduced in the 90?min exercise group, but it was significantly higher in groups with 120 and 150 min exercise compared to that of 90 min exercise group. The activity of SOD was not significantly affected. The results indicate that acute exercise increases mitochondrial H2O2 production in the skeletal muscle, which is associated with the upregulation of p66Shc and FOXO3a. The association of p66Shc and FOXO3a signaling with exercise induced H2O2 generation may play a role in regulating cellular oxidative stress during acute exercise.

Wang, Ping; Qi, Zhengtang; Cui, Di; Ding, Shuzhe

2015-01-01

36

Mitochondrial Biogenesis in the Pulmonary Vasculature During Inhalational Lung Injury and Fibrosis  

PubMed Central

Cell survival and injury repair is facilitated by mitochondrial biogenesis; however, the role of this process in lung repair is unknown. We evaluated mitochondrial biogenesis in the mouse lung in two injuries that cause acute inflammation and in two that cause chronic inflammation and pulmonary fibrosis. By using reporter mice that express green fluorescent protein (GFP) exclusively in mitochondria, we tracked mitochondrial biogenesis and correlated it with histologic lung injury, proliferation, and fibrosis. At 72 hours after acute LPS or continuous exposure to hyperoxia (Fio2, 1.0), the lungs showed diffuse infiltration by inflammatory cells in the alveolar region. In reporter mice, patchy new mitochondrial fluorescence was found in the alveolar region but was most prominent and unexpected in perivascular regions. At 14 days after instillation of asbestos or bleomycin, diffuse chronic inflammation had developed, and green fluorescence appeared in inflammatory cells in the expanded interstitium and was most intense in smooth muscle cells of pulmonary vessels. In all four lung injuries, mitochondrial fluorescence colocalized with mitochondrial superoxide dismutase, but not with proliferating cell nuclear antigen. These data indicate that vascular mitochondrial biogenesis is activated in diverse inhalational lung injuries along with oxidative stress. This finding indicates a unique and unexpected mechanism of metabolic adaptation to pulmonary fibrotic injuries. PMID:17999632

CARRAWAY, MARTHA S.; SULIMAN, HAGIR B.; KLIMENT, CORRINE; WELTY-WOLF, KAREN E.; OURY, TIM D.; PIANTADOSI, CLAUDE A.

2008-01-01

37

Reactive oxygen species mediates homocysteine-induced mitochondrial biogenesis in human endothelial cells: Modulation by antioxidants  

SciTech Connect

It has been proposed that homocysteine (Hcy)-induces endothelial dysfunction and atherosclerosis by generation of reactive oxygen species (ROS). A previous report has shown that Hcy promotes mitochondrial damage. Considering that oxidative stress can affect mitochondrial biogenesis, we hypothesized that Hcy-induced ROS in endothelial cells may lead to increased mitochondrial biogenesis. We found that Hcy-induced ROS (1.85-fold), leading to a NF-{kappa}B activation and increase the formation of 3-nitrotyrosine. Furthermore, expression of the mitochondrial biogenesis factors, nuclear respiratory factor-1 and mitochondrial transcription factor A, was significantly elevated in Hcy-treated cells. These changes were accompanied by increase in mitochondrial mass and higher mRNA and protein expression of the subunit III of cytochrome c oxidase. These effects were significantly prevented by pretreatment with the antioxidants, catechin and trolox. Taken together, our results suggest that ROS is an important mediator of mitochondrial biogenesis induced by Hcy, and that modulation of oxidative stress by antioxidants may protect against the adverse vascular effects of Hcy.

Perez-de-Arce, Karen [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile); Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile); Foncea, Rocio [Departamento de Nutricion, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Catolica de Chile, Santiago (Chile)]. E-mail: rfoncea@med.puc.cl; Leighton, Federico [Departamento de Biologia Celular y Molecular, Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Santiago (Chile)

2005-12-16

38

The Effects of NAD+ on Apoptotic Neuronal Death and Mitochondrial Biogenesis and Function after Glutamate Excitotoxicity  

PubMed Central

NAD+ is an essential co-enzyme for cellular energy metabolism and is also involved as a substrate for many cellular enzymatic reactions. It has been shown that NAD+ has a beneficial effect on neuronal survival and brain injury in in vitro and in vivo ischemic models. However, the effect of NAD+ on mitochondrial biogenesis and function in ischemia has not been well investigated. In the present study, we used an in vitro glutamate excitotoxicity model of primary cultured cortical neurons to study the effect of NAD+ on apoptotic neuronal death and mitochondrial biogenesis and function. Our results show that supplementation of NAD+ could effectively reduce apoptotic neuronal death, and apoptotic inducing factor translocation after neurons were challenged with excitotoxic glutamate stimulation. Using different approaches including confocal imaging, mitochondrial DNA measurement and Western blot analysis of PGC-1 and NRF-1, we also found that NAD+ could significantly attenuate glutamate-induced mitochondrial fragmentation and the impairment of mitochondrial biogenesis. Furthermore, NAD+ treatment effectively inhibited mitochondrial membrane potential depolarization and NADH redistribution after excitotoxic glutamate stimulation. Taken together, our results demonstrated that NAD+ is capable of inhibiting apoptotic neuronal death after glutamate excitotoxicity via preserving mitochondrial biogenesis and integrity. Our findings provide insights into potential neuroprotective strategies in ischemic stroke. PMID:25387075

Wang, Xiaowan; Li, Hailong; Ding, Shinghua

2014-01-01

39

Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC1  

Microsoft Academic Search

Mitochondrial number and function are altered in response to external stimuli in eukaryotes. While several transcription\\/replication factors directly regulate mitochondrial genes, the coordination of these factors into a program responsive to the environment is not understood. We show here that PGC-1, a cold-inducible coactivator of nuclear receptors, stimulates mitochondrial biogenesis and respiration in muscle cells through an induction of uncoupling

Zhidan Wu; Pere Puigserver; Ulf Andersson; Chenyu Zhang; Guillaume Adelmant; Vamsi Mootha; Amy Troy; Saverio Cinti; Bradford Lowell; Richard C. Scarpulla; Bruce M. Spiegelman

1999-01-01

40

Exercise-Mediated Wall Shear Stress Increases Mitochondrial Biogenesis in Vascular Endothelium  

PubMed Central

Objective Enhancing structural and functional integrity of mitochondria is an emerging therapeutic option against endothelial dysfunction. In this study, we sought to investigate the effect of fluid shear stress on mitochondrial biogenesis and mitochondrial respiratory function in endothelial cells (ECs) using in vitro and in vivo complementary studies. Methods and Results Human aortic- or umbilical vein-derived ECs were exposed to laminar shear stress (20 dyne/cm2) for various durations using a cone-and-plate shear apparatus. We observed significant increases in the expression of key genes related to mitochondrial biogenesis and mitochondrial quality control as well as mtDNA content and mitochondrial mass under the shear stress conditions. Mitochondrial respiratory function was enhanced when cells were intermittently exposed to laminar shear stress for 72 hrs. Also, shear-exposed cells showed diminished glycolysis and decreased mitochondrial membrane potential (??m). Likewise, in in vivo experiments, mice that were subjected to a voluntary wheel running exercise for 5 weeks showed significantly higher mitochondrial content determined by en face staining in the conduit (greater and lesser curvature of the aortic arch and thoracic aorta) and muscle feed (femoral artery) arteries compared to the sedentary control mice. Interestingly, however, the mitochondrial biogenesis was not observed in the mesenteric artery. This region-specific adaptation is likely due to the differential blood flow redistribution during exercise in the different vessel beds. Conclusion Taken together, our findings suggest that exercise enhances mitochondrial biogenesis in vascular endothelium through a shear stress-dependent mechanism. Our findings may suggest a novel mitochondrial pathway by which a chronic exercise may be beneficial for vascular function. PMID:25375175

Kim, Boa; Lee, Hojun; Kawata, Keisuke; Park, Joon-Young

2014-01-01

41

Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice  

PubMed Central

Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity. PMID:25780774

Wu, Ming; Li, Si-Ming; Gao, Qian

2015-01-01

42

Artemisinin mimics calorie restriction to trigger mitochondrial biogenesis and compromise telomere shortening in mice.  

PubMed

Calorie restriction is known to extend lifespan among organisms by a debating mechanism underlying nitric oxide-driven mitochondrial biogenesis. We report here that nitric oxide generators including artemisinin, sodium nitroprusside, and L-arginine mimics calorie restriction and resembles hydrogen peroxide to initiate the nitric oxide signaling cascades and elicit the global antioxidative responses in mice. The large quantities of antioxidant enzymes are correlated with the low levels of reactive oxygen species, which allow the down-regulation of tumor suppressors and accessory DNA repair partners, eventually leading to the compromise of telomere shortening. Accompanying with the up-regulation of signal transducers and respiratory chain signatures, mitochondrial biogenesis occurs with the elevation of adenosine triphosphate levels upon exposure of mouse skeletal muscles to the mimetics of calorie restriction. In conclusion, calorie restriction-triggered nitric oxide provides antioxidative protection and alleviates telomere attrition via mitochondrial biogenesis, thereby maintaining chromosomal stability and integrity, which are the hallmarks of longevity. PMID:25780774

Wang, Da-Ting; He, Jiang; Wu, Ming; Li, Si-Ming; Gao, Qian; Zeng, Qing-Ping

2015-01-01

43

Augmentation of aerobic respiration and mitochondrial biogenesis in skeletal muscle by hypoxia preconditioning with cobalt chloride  

SciTech Connect

High altitude/hypoxia training is known to improve physical performance in athletes. Hypoxia induces hypoxia inducible factor-1 (HIF-1) and its downstream genes that facilitate hypoxia adaptation in muscle to increase physical performance. Cobalt chloride (CoCl{sub 2}), a hypoxia mimetic, stabilizes HIF-1, which otherwise is degraded in normoxic conditions. We studied the effects of hypoxia preconditioning by CoCl{sub 2} supplementation on physical performance, glucose metabolism, and mitochondrial biogenesis using rodent model. The results showed significant increase in physical performance in cobalt supplemented rats without (two times) or with training (3.3 times) as compared to control animals. CoCl{sub 2} supplementation in rats augmented the biological activities of enzymes of TCA cycle, glycolysis and cytochrome c oxidase (COX); and increased the expression of glucose transporter-1 (Glut-1) in muscle showing increased glucose metabolism by aerobic respiration. There was also an increase in mitochondrial biogenesis in skeletal muscle observed by increased mRNA expressions of mitochondrial biogenesis markers which was further confirmed by electron microscopy. Moreover, nitric oxide production increased in skeletal muscle in cobalt supplemented rats, which seems to be the major reason for peroxisome proliferator activated receptor-gamma coactivator-1? (PGC-1?) induction and mitochondrial biogenesis. Thus, in conclusion, we state that hypoxia preconditioning by CoCl{sub 2} supplementation in rats increases mitochondrial biogenesis, glucose uptake and metabolism by aerobic respiration in skeletal muscle, which leads to increased physical performance. The significance of this study lies in understanding the molecular mechanism of hypoxia adaptation and improvement of work performance in normal as well as extreme conditions like hypoxia via hypoxia preconditioning. -- Highlights: ? We supplemented rats with CoCl{sub 2} for 15 days along with training. ? CoCl{sub 2} supplementation augmented endurance performance and aerobic respiration. ? It increased glucose uptake and metabolism in muscle. ? It enhanced mitochondrial biogenesis in red gastrocnemius muscle.

Saxena, Saurabh [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)] [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India); Shukla, Dhananjay [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India)] [Department of Biotechnology, Gitam University, Gandhi Nagar, Rushikonda, Visakhapatnam-530 045 Andhra Pradesh (India); Bansal, Anju, E-mail: anjubansaldipas@gmail.com [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)] [Experimental Biology Division, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 (India)

2012-11-01

44

Opposite effects of 17-? estradiol and testosterone on mitochondrial biogenesis and adiponectin synthesis in white adipocytes.  

PubMed

Sexual dimorphism has been found in both mitochondrial functionality and adiponectin expression in white adipose tissue, with female rats presenting more functional mitochondria than males and greater adiponectin expression. However, little is known about the role of sex hormones in this dimorphism. The aim was to elucidate the role of sex hormones in mitochondrial biogenesis and dynamics and in adiponectin synthesis in white adipocytes, and also to provide new evidence of the link between these processes. 3T3-L1 preadipocytes were differentiated and treated either with 17-? estradiol (E?; 10? nM), progesterone (Pg), testosterone (1? ?M both), or a combination of Pg or testosterone with flutamide (FLT; 10? ?M) or E? (1? ?M). The markers of mitochondrial biogenesis and dynamics and adiponectin expression were analyzed. E? induced mitochondrial proliferation and differentiation in 3T3-L1, although testosterone showed opposite effects. Pg treatment stimulated proliferation but impaired differentiation. In concerns mitochondrial dynamics, these hormones promoted fusion over fission. FLT treatment indicated that Pg elicits its effects on mitochondrial dynamics through the androgen receptor. E? coadministration with testosterone or Pg reversed its effects. In conclusion, our results show that E? induces stimulation of mitochondrial biogenesis in white adipocytes in vitro, especially in situations that imply an impairment of mitochondrial function, whereas testosterone would have opposite effects. Moreover, testosterone and Pg alter mitochondrial dynamics by promoting fusion over fission, while E? stimulates both processes. All these alterations run in parallel with changes in adiponectin expression, thus suggesting the existence of a link between mitochondrial biogenesis and dynamics and adiponectin synthesis in white adipocytes. PMID:24604890

Capllonch-Amer, Gabriela; Lladó, Isabel; Proenza, Ana M; García-Palmer, Francisco J; Gianotti, Magdalena

2014-04-01

45

Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe S clusters in  

E-print Network

Jac1, a mitochondrial J-type chaperone, is involved in the biogenesis of Fe S clusters, Poland Contributed by Elizabeth A. Craig, November 28, 2000 A minor Hsp70 chaperone of the mitochondrial and or mitochondrial iron metabolism. Here, we report evidence that Jac1, a J-type chaperone of the mitochondrial

Craig, Elizabeth A

46

Suppression of polyglutamine-induced cytotoxicity in Saccharomyces cerevisiae by enhancement of mitochondrial biogenesis.  

PubMed

Alterations in mitochondrial metabolism have been associated with age-related neurodegenerative disorders. This is seen in diseases caused by misfolding of proteins with expanded polyglutamine (polyQ) tracts, such as Huntington's disease. Although evidence of mitochondrial impairment has been extensively documented in patients and disease models, the mechanisms involved and their relevance to the initiation of polyQ cytotoxicity and development of clinical manifestations remain controversial. We report that in yeast models of polyQ cytotoxicity, wild-type and mutant polyQ domains might associate early with the outer mitochondrial membrane. The association of mutant domains with mitochondrial membranes could contribute to induce significant changes in mitochondrial physiology, ultimately compromising the cell's ability to respire. The respiratory defect can be fully prevented by enhancing mitochondrial biogenesis by overexpression of Hap4p, the catalytic subunit of the transcriptional activator Hap2/3/4/5p complex, the master regulator of the expression of many nuclear genes encoding mitochondrial proteins in yeast. Protecting cellular respiratory capacity in this way ameliorates the effect of expanded polyQ on cellular fitness. We conclude that mitochondrial dysfunction is an important contributor to polyQ cytotoxicity. Our results suggest that therapeutic approaches enhancing mitochondrial biogenesis could reduce polyQ toxicity and delay the development of clinical symptoms in patients. PMID:20008543

Ocampo, Alejandro; Zambrano, Andrea; Barrientos, Antoni

2010-05-01

47

Efficient mitochondrial biogenesis drives incomplete penetrance in Leber’s hereditary optic neuropathy  

PubMed Central

Leber’s hereditary optic neuropathy is a maternally inherited blinding disease caused as a result of homoplasmic point mutations in complex I subunit genes of mitochondrial DNA. It is characterized by incomplete penetrance, as only some mutation carriers become affected. Thus, the mitochondrial DNA mutation is necessary but not sufficient to cause optic neuropathy. Environmental triggers and genetic modifying factors have been considered to explain its variable penetrance. We measured the mitochondrial DNA copy number and mitochondrial mass indicators in blood cells from affected and carrier individuals, screening three large pedigrees and 39 independently collected smaller families with Leber’s hereditary optic neuropathy, as well as muscle biopsies and cells isolated by laser capturing from post-mortem specimens of retina and optic nerves, the latter being the disease targets. We show that unaffected mutation carriers have a significantly higher mitochondrial DNA copy number and mitochondrial mass compared with their affected relatives and control individuals. Comparative studies of fibroblasts from affected, carriers and controls, under different paradigms of metabolic demand, show that carriers display the highest capacity for activating mitochondrial biogenesis. Therefore we postulate that the increased mitochondrial biogenesis in carriers may overcome some of the pathogenic effect of mitochondrial DNA mutations. Screening of a few selected genetic variants in candidate genes involved in mitochondrial biogenesis failed to reveal any significant association. Our study provides a valuable mechanism to explain variability of penetrance in Leber’s hereditary optic neuropathy and clues for high throughput genetic screening to identify the nuclear modifying gene(s), opening an avenue to develop predictive genetic tests on disease risk and therapeutic strategies. PMID:24369379

Iommarini, Luisa; Giordano, Luca; Maresca, Alessandra; Pisano, Annalinda; Valentino, Maria Lucia; Caporali, Leonardo; Liguori, Rocco; Deceglie, Stefania; Roberti, Marina; Fanelli, Francesca; Fracasso, Flavio; Ross-Cisneros, Fred N.; D’Adamo, Pio; Hudson, Gavin; Pyle, Angela; Yu-Wai-Man, Patrick; Chinnery, Patrick F.; Zeviani, Massimo; Salomao, Solange R.; Berezovsky, Adriana; Belfort, Rubens; Ventura, Dora Fix; Moraes, Milton; Moraes Filho, Milton; Barboni, Piero; Sadun, Federico; De Negri, Annamaria; Sadun, Alfredo A.; Tancredi, Andrea; Mancini, Massimiliano; d’Amati, Giulia; Loguercio Polosa, Paola; Cantatore, Palmiro

2014-01-01

48

Exercise-Induced Urticaria  

MedlinePLUS

MENU Return to Web version Exercise-induced Urticaria Overview What is exercise-induced urticaria? Exercise-induced urticaria is a condition that causes hives and other allergic symptoms. It can occur during ...

49

Nebivolol stimulates mitochondrial biogenesis in 3T3-L1 adipocytes  

SciTech Connect

Highlights: •Nebivolol may act as a partial agonist of ?3-adrenergic receptor (AR). •Nebivolol stimulates mitochondrial DNA replication and protein expression. •Nebivolol promotes mitochondrial synthesis via activation of eNOS by ?3-AR. -- Abstract: Nebivolol is a third-generation ?-adrenergic receptor (?-AR) blocker with additional beneficial effects, including the improvement of lipid and glucose metabolism in obese individuals. However, the underlying mechanism of nebivolol’s role in regulating the lipid profile remains largely unknown. In this study, we investigated the role of nebivolol in mitochondrial biogenesis in 3T3-L1 adipocytes. Exposure of 3T3-L1 cells to nebivolol for 24 h increased mitochondrial DNA copy number, mitochondrial protein levels and the expression of transcription factors involved in mitochondrial biogenesis, including PPAR-? coactivator-1? (PGC-1?), Sirtuin 3 (Sirt3), mitochondrial transcription factor A (Tfam) and nuclear related factor 1 (Nrf1). These changes were accompanied by an increase in oxygen consumption and in the expression of genes involved in fatty acid oxidation and antioxidant enzymes in 3T3-L1 adipocytes, including nebivolol-induced endothelial nitric oxide synthase (eNOS), as well as an increase in the formation of cyclic guanosine monophosphate (cGMP). Pretreatment with NG-nitro-L-arginine methyl ester (l-NAME) attenuated nebivolol-induced mitochondrial biogenesis, as did the soluble guanylate cyclase inhibitor, ODQ. Treatment with nebivolol and ?3-AR blocker SR59230A markedly attenuated PGC-1?, Sirt3 and manganese superoxide dismutase (MnSOD) protein levels in comparison to treatment with nebivolol alone. These data indicate that the mitochondrial synthesis and metabolism in adipocytes that is promoted by nebivolol is primarily mediated through the eNOS/cGMP-dependent pathway and is initiated by the activation of ?3-AR receptors.

Huang, Chenglin; Chen, Dongrui; Xie, Qihai [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)] [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Yang, Ying, E-mail: yangying_sh@yahoo.com [Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)] [Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China); Shen, Weili, E-mail: weili_shen@hotmail.com [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)] [State Key Laboratory of Medical Genomics, Shanghai Key Laboratory of Vascular Biology, Department of Hypertension, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200025 (China)

2013-08-16

50

Short Term Exercise Induces PGC-1?, Ameliorates Inflammation and Increases Mitochondrial Membrane Proteins but Fails to Increase Respiratory Enzymes in Aging Diabetic Hearts  

PubMed Central

PGC-1?, a transcriptional coactivator, controls inflammation and mitochondrial gene expression in insulin-sensitive tissues following exercise intervention. However, attributing such effects to PGC-1? is counfounded by exercise-induced fluctuations in blood glucose, insulin or bodyweight in diabetic patients. The goal of this study was to investigate the role of PGC-1? on inflammation and mitochondrial protein expressions in aging db/db mice hearts, independent of changes in glycemic parameters. In 8-month-old db/db mice hearts with diabetes lasting over 22 weeks, short-term, moderate-intensity exercise upregulated PGC-1? without altering body weight or glycemic parameters. Nonetheless, such a regimen lowered both cardiac (macrophage infiltration, iNOS and TNF?) and systemic (circulating chemokines and cytokines) inflammation. Curiously, such an anti-inflammatory effect was also linked to attenuated expression of downstream transcription factors of PGC-1? such as NRF-1 and several respiratory genes. Such mismatch between PGC-1? and its downstream targets was associated with elevated mitochondrial membrane proteins like Tom70 but a concurrent reduction in oxidative phosphorylation protein expressions in exercised db/db hearts. As mitochondrial oxidative stress was predominant in these hearts, in support of our in vivo data, increasing concentrations of H2O2 dose-dependently increased PGC-1? expression while inhibiting expression of inflammatory genes and downstream transcription factors in H9c2 cardiomyocytes in vitro. We conclude that short-term exercise-induced oxidative stress may be key in attenuating cardiac inflammatory genes and impairing PGC-1? mediated gene transcription of downstream transcription factors in type 2 diabetic hearts at an advanced age. PMID:23936397

Botta, Amy; Laher, Ismail; Beam, Julianne; DeCoffe, Daniella; Brown, Kirsty; Halder, Swagata; Devlin, Angela; Gibson, Deanna L.; Ghosh, Sanjoy

2013-01-01

51

Leucine Modulates Mitochondrial Biogenesis and SIRT1-AMPK Signaling in C2C12 Myotubes.  

PubMed

Previous studies from this laboratory demonstrate that dietary leucine protects against high fat diet-induced mitochondrial impairments and stimulates mitochondrial biogenesis and energy partitioning from adipocytes to muscle cells through SIRT1-mediated mechanisms. Moreover, ?-hydroxy-?-methyl butyrate (HMB), a metabolite of leucine, has been reported to activate AMPK synergistically with resveratrol in C2C12 myotubes. Therefore, we hypothesize that leucine-induced activation of SIRT1 and AMPK is the central event that links the upregulated mitochondrial biogenesis and fatty acid oxidation in skeletal muscle. Thus, C2C12 myotubes were treated with leucine (0.5?mM), alanine (0.5?mM), valine (0.5?mM), EX527 (SIRT1 inhibitor, 25??M), and Compound C (AMPK inhibitor, 25??M) alone or in combination to determine the roles of AMPK and SIRT1 in leucine-modulation of energy metabolism. Leucine significantly increased mitochondrial content, mitochondrial biogenesis-related genes expression, fatty acid oxidation, SIRT1 activity and gene expression, and AMPK phosphorylation in C2C12 myotubes compared to the controls, while EX527 and Compound C markedly attenuated these effects. Furthermore, leucine treatment for 24 hours resulted in time-dependent increases in cellular NAD(+), SIRT1 activity, and p-AMPK level, with SIRT1 activation preceding that of AMPK, indicating that leucine activation of SIRT1, rather than AMPK, is the primary event. PMID:25400942

Liang, Chunzi; Curry, Benjamin J; Brown, Patricia L; Zemel, Michael B

2014-01-01

52

Cilostazol promotes mitochondrial biogenesis in human umbilical vein endothelial cells through activating the expression of PGC-1?  

SciTech Connect

Highlights: ? First time to show that cilostazol promotes the expressions of PGC-1?. ? First time to show that cilostazol stimulates mitochondrial biogenesis in HUVECs. ? PKA/CREB pathway mediates the effect of cilostazol on PGC-1? expression. ? Suggesting the roles of cilostazol in mitochondrial dysfunction related disease. -- Abstract: Mitochondrial dysfunction is frequently observed in vascular diseases. Cilostazol is a drug approved by the US Food and Drug Administration for the treatment of intermittent claudication. Cilostazol increases intracellular cyclic adenosine monophosphate (cAMP) levels through inhibition of type III phosphodiesterase. The effects of cilostazol in mitochondrial biogenesis in human umbilical vein endothelial cells (HUVECs) were investigated in this study. Cilostazol treated HUVECs displayed increased levels of ATP, mitochondrial DNA/nuclear DNA ratio, expressions of cytochrome B, and mitochondrial mass, suggesting an enhanced mitochondrial biogenesis induced by cilostazol. The promoted mitochondrial biogenesis could be abolished by Protein kinase A (PKA) specific inhibitor H-89, implying that PKA pathway played a critical role in increased mitochondrial biogenesis after cilostazol treatment. Indeed, expression levels of peroxisome proliferator activator receptor gamma-coactivator 1? (PGC-1?), NRF 1 and mitochondrial transcription factor A (TFAM) were significantly increased in HUVECs after incubation with cilostazol at both mRNA levels and protein levels. Importantly, knockdown of PGC-1? could abolish cilostazol-induced mitochondrial biogenesis. Enhanced expression of p-CREB and PGC-1? induced by cilostazol could be inhibited by H-89. Moreover, the increased expression of PGC-1? induced by cilostazol could be inhibited by downregulation of CREB using CREB siRNA at both mRNA and protein levels. All the results indicated that cilostazol promoted mitochondrial biogenesis through activating the expression of PGC-1? in HUVECs, which was mediated by PKA/CREB pathway.

Zuo, Luning [Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China) [Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China); Department of Cardiology, Yantaishan Hospital, Yantai, Shandong 264001 (China); Li, Qiang; Sun, Bei; Xu, Zhiying [Department of Cardiology, Yantaishan Hospital, Yantai, Shandong 264001 (China)] [Department of Cardiology, Yantaishan Hospital, Yantai, Shandong 264001 (China); Ge, Zhiming, E-mail: zhimingge2000@hotmail.com [Department of Cardiology, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)] [Department of Cardiology, Qilu Hospital, Shandong University, 44 Wenhua Xi Road, Jinan, Shandong 250012 (China)

2013-03-29

53

PGC-1? mediates mitochondrial biogenesis and oxidative phosphorylation to promote metastasis  

PubMed Central

Cancer cells can divert metabolites into anabolic pathways to support their rapid proliferation and to accumulate the cellular building blocks required for tumor growth. However, the specific bioenergetic profile of invasive and metastatic cancer cells is unknown. Here we report that migratory/invasive cancer cells specifically favor mitochondrial respiration and increased ATP production. Invasive cancer cells use transcription co-activator, PGC-1? to enhance oxidative phosphorylation, mitochondrial biogenesis and oxygen consumption rate. Clinical analysis of human invasive breast cancers revealed a strong correlation between PGC-1? expression in invasive cancer cells and formation of distant metastases. Silencing of PGC-1? in cancer cells suspended their invasive potential and attenuated metastasis without affecting proliferation, primary tumor growth or epithelial-to-mesenchymal (EMT) program. While inherent genetics of cancer cells determine the transcriptome framework required for invasion and metastasis, mitochondrial biogenesis and respiration induced by PGC-1? is also essential for functional motility of cancer cells and metastasis. PMID:25241037

LeBleu, Valerie S.; O'Connell, Joyce T.; Herrera, Karina N. Gonzalez; Wikman-Kocher, Harriet; Pantel, Klaus; Haigis, Marcia C.; de Carvalho, Fernanda Machado; Damascena, Aline; Chinen, Ludmilla Thome Domingos; Rocha, Rafael M.; Asara, John M.; Kalluri, Raghu

2014-01-01

54

Mitochondrial Biogenesis: Regulation By Endogenous Gases during Inflammation and Organ Stress  

PubMed Central

The influence of mitochondrial dysfunction on pathological states involving inflammatory and/or oxidative stress in tissues that do not show frank cellular apoptosis or necrosis has been rather difficult to unravel, and the literature is replete with contradictory information. Although such discrepancies have many potential causes related to the type of injurious agent, the severity and duration of the injury, and the particular cells and tissues and the functions involved, it is the successful induction of cellular adaptive responses that ultimately governs the resolution of mitochondrial dysfunction and survival of the cell. Much recent attention has been devoted to unraveling the signaling pathways that activate mitochondrial biogenesis and other processes involved in mitochondrial quality control (QC) during inflammatory and oxidative stress with an eye towards the development of novel targets for therapeutic mitigation of the resultant tissue damage. This review provides a brief overview of this emerging field with an emphasis on the role of signaling through the endogenous gases (NO, CO and H2S) and a redox-based approach that brings transparency to key factors that contribute to the resolution of mitochondrial dysfunction and the maintenance of cell vitality. We make the case that targeted stimulation of mitochondrial biogenesis could be a potentially valuable approach for the development of new therapies for the treatment of diseases for which mitochondrial damage is a major consideration. PMID:24606800

Suliman, Hagir B.; Piantadosi, Claude A.

2014-01-01

55

GABP Transcription Factor (Nuclear Respiratory Factor 2) Is Required for Mitochondrial Biogenesis  

PubMed Central

Mitochondria are membrane-bound cytoplasmic organelles that serve as the major source of ATP production in eukaryotic cells. GABP (also known as nuclear respiratory factor 2) is a nuclear E26 transformation-specific transcription factor (ETS) that binds and activates mitochondrial genes that are required for electron transport and oxidative phosphorylation. We conditionally deleted Gabpa, the DNA-binding component of this transcription factor complex, from mouse embryonic fibroblasts (MEFs) to examine the role of Gabp in mitochondrial biogenesis, function, and gene expression. Gabp? loss modestly reduced mitochondrial mass, ATP production, oxygen consumption, and mitochondrial protein synthesis but did not alter mitochondrial morphology, membrane potential, apoptosis, or the expression of several genes that were previously reported to be GABP targets. However, the expression of Tfb1m, a methyltransferase that modifies ribosomal rRNA and is required for mitochondrial protein translation, was markedly reduced in Gabp?-null MEFs. We conclude that Gabp regulates Tfb1m expression and plays an essential, nonredundant role in mitochondrial biogenesis. PMID:24958105

Yang, Zhong-Fa; Drumea, Karen; Mott, Stephanie; Wang, Junling

2014-01-01

56

Salidroside stimulates mitochondrial biogenesis and protects against H?O?-induced endothelial dysfunction.  

PubMed

Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. The purpose of this study is to explore the mechanism of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cytotoxicity brought by H2O2. Functional studies on the rat aortas found that SAL rescued the endothelium-dependent relaxation and reduced superoxide anion (O2(?-)) production induced by H2O2. Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production. The underlying mechanisms involve the inhibition of H2O2-induced activation of endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the redox sensitive transcription factor, NF-kappa B (NF- ? B). SAL also increased mitochondrial mass and upregulated the mitochondrial biogenesis factors, peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1 ? ), and mitochondrial transcription factor A (TFAM) in the endothelial cells. H2O2-induced mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane potential (? ? m) and ATP production, was rescued by SAL pretreatment. Taken together, these findings implicate that SAL could protect endothelium against H2O2-induced injury via promoting mitochondrial biogenesis and function, thus preventing the overactivation of oxidative stress-related downstream signaling pathways. PMID:24868319

Xing, Shasha; Yang, Xiaoyan; Li, Wenjing; Bian, Fang; Wu, Dan; Chi, Jiangyang; Xu, Gao; Zhang, Yonghui; Jin, Si

2014-01-01

57

Salidroside Stimulates Mitochondrial Biogenesis and Protects against H2O2-Induced Endothelial Dysfunction  

PubMed Central

Salidroside (SAL) is an active component of Rhodiola rosea with documented antioxidative properties. The purpose of this study is to explore the mechanism of the protective effect of SAL on hydrogen peroxide- (H2O2-) induced endothelial dysfunction. Pretreatment of the human umbilical vein endothelial cells (HUVECs) with SAL significantly reduced the cytotoxicity brought by H2O2. Functional studies on the rat aortas found that SAL rescued the endothelium-dependent relaxation and reduced superoxide anion (O2??) production induced by H2O2. Meanwhile, SAL pretreatment inhibited H2O2-induced nitric oxide (NO) production. The underlying mechanisms involve the inhibition of H2O2-induced activation of endothelial nitric oxide synthase (eNOS), adenosine monophosphate-activated protein kinase (AMPK), and Akt, as well as the redox sensitive transcription factor, NF-kappa B (NF-?B). SAL also increased mitochondrial mass and upregulated the mitochondrial biogenesis factors, peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1?), and mitochondrial transcription factor A (TFAM) in the endothelial cells. H2O2-induced mitochondrial dysfunction, as demonstrated by reduced mitochondrial membrane potential (??m) and ATP production, was rescued by SAL pretreatment. Taken together, these findings implicate that SAL could protect endothelium against H2O2-induced injury via promoting mitochondrial biogenesis and function, thus preventing the overactivation of oxidative stress-related downstream signaling pathways. PMID:24868319

Xing, Shasha; Yang, Xiaoyan; Li, Wenjing; Bian, Fang; Wu, Dan; Chi, Jiangyang; Xu, Gao; Zhang, Yonghui; Jin, Si

2014-01-01

58

High concentration of gadolinium ion modifying isolated rice mitochondrial biogenesis.  

PubMed

Mitochondria play an important role in plant growth and development, cooperating with the endoplasmic reticulum and nucleus. Gadolinium, one of the rare earth elements, is an inhibitor of stretch-activated calcium channels located on the endoplasmic reticulum and plasma membrane and has no effect on nuclear calcium variation in plant cells. We analyzed the effects of Gd3+ on mitochondria function by monitoring mitochondrial swelling, changes of membrane fluidity, and transmembrane potential collapse and by observing mitochondrial ultrastructure. We found that high concentration of Gd3+ induces rice mitochondrial dysfunction through mitochondrial permeability transition (MPT). The protection of DTT and EDTA demonstrate that Gd3+ blocks the inner membrane ion channel through thiol chelation. PMID:24078325

Zhao, Jie; Jin, Jian-Cheng; Zhou, Zhi-Qiang; Xia, Cai-Fen; Yang, Xiao-Gang; Jiang, Feng-Lei; Dai, Jie; Liu, Yi

2013-12-01

59

Mitochondrial DNA copy numbers in pyramidal neurons are decreased and mitochondrial biogenesis transcriptome signaling is disrupted in Alzheimer's disease hippocampi.  

PubMed

Alzheimer's disease (AD) is the major cause of adult-onset dementia and is characterized in its pre-diagnostic stage by reduced cerebral cortical glucose metabolism and in later stages by reduced cortical oxygen uptake, implying reduced mitochondrial respiration. Using quantitative PCR we determined the mitochondrial DNA (mtDNA) gene copy numbers from multiple groups of 15 or 20 pyramidal neurons, GFAP(+) astrocytes and dentate granule neurons isolated using laser capture microdissection, and the relative expression of mitochondrial biogenesis (mitobiogenesis) genes in hippocampi from 10 AD and 9 control (CTL) cases. AD pyramidal but not dentate granule neurons had significantly reduced mtDNA copy numbers compared to CTL neurons. Pyramidal neuron mtDNA copy numbers in CTL, but not AD, positively correlated with cDNA levels of multiple mitobiogenesis genes. In CTL, but not in AD, hippocampal cDNA levels of PGC1? were positively correlated with multiple downstream mitobiogenesis factors. Mitochondrial DNA copy numbers in pyramidal neurons did not correlate with hippocampal A?1-42 levels. After 48 h exposure of H9 human neural stem cells to the neurotoxic fragment A?25-35, mtDNA copy numbers were not significantly altered. In summary, AD postmortem hippocampal pyramidal neurons have reduced mtDNA copy numbers. Mitochondrial biogenesis pathway signaling relationships are disrupted in AD, but are mostly preserved in CTL. Our findings implicate complex alterations of mitochondria-host cell relationships in AD. PMID:24448779

Rice, Ann C; Keeney, Paula M; Algarzae, Norah K; Ladd, Amy C; Thomas, Ravindar R; Bennett, James P

2014-01-01

60

Turn up the power –pharmacological activation of mitochondrial biogenesis in mouse models  

PubMed Central

The oxidative phosphorylation (OXPHOS) system in mitochondria is responsible for the generation of the majority of cellular energy in the form of ATP. Patients with genetic OXPHOS disorders form the largest group of inborn errors of metabolism. Unfortunately, there is still a lack of efficient therapies for these disorders other than management of symptoms. Developing therapies has been complicated because, although the total group of OXPHOS patients is relatively large, there is enormous clinical and genetic heterogeneity within this patient population. Thus there has been a lot of interest in generating relevant mouse models for the different kinds of OXPHOS disorders. The most common treatment strategies tested in these mouse models have aimed to up-regulate mitochondrial biogenesis, in order to increase the residual OXPHOS activity present in affected animals and thereby to ameliorate the energy deficiency. Drugs such as bezafibrate, resveratrol and AICAR target the master regulator of mitochondrial biogenesis PGC-1? either directly or indirectly to manipulate mitochondrial metabolism. This review will summarize the outcome of preclinical treatment trials with these drugs in mouse models of OXPHOS disorders and discuss similar treatments in a number of mouse models of common diseases in which pathology is closely linked to mitochondrial dysfunction. In the majority of these studies the pharmacological activation of the PGC-1? axis shows true potential as therapy; however, other effects besides mitochondrial biogenesis may be contributing to this as well. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24102298

Komen, J C; Thorburn, D R

2014-01-01

61

Neural stem cell transplantation enhances mitochondrial biogenesis in a transgenic mouse model of Alzheimer's disease-like pathology.  

PubMed

Mitochondrial dysfunction, especially a defect in mitochondrial biogenesis, is an early and prominent feature of Alzheimer's disease (AD). Previous studies demonstrated that the number of mitochondria is significantly reduced in susceptible hippocampal neurons from AD patients. Neural stem cell (NSC) transplantation in AD-like mice can compensate for the neuronal loss resulting from amyloid-beta protein deposition. The effects of NSC transplantation on mitochondrial biogenesis and cognitive function in AD-like mice, however, are poorly understood. In this study, we injected NSCs or vehicle into 12-month-old amyloid precursor protein (APP)/PS1 transgenic mice, a mouse model of AD-like pathology. The effects of NSC transplantation on cognitive function, the amount of mitochondrial DNA, the expression of mitochondrial biogenesis factors and mitochondria-related proteins, and mitochondrial morphology were investigated. Our results show that in NSC-injected APP/PS1 (Tg-NSC) mice, the cognitive function, number of mitochondria, and expression of mitochondria-related proteins, specifically the mitochondrial fission factors (dynamin-related protein 1 [Drp1] and fission 1 [Fis1]) and the mitochondrial fusion factor optic atrophy 1 (OPA1), were significantly increased compared with those in age-matched vehicle-injected APP/PS1 (Tg-Veh) mice, whereas the expression of mitochondrial fusion factors mitofusion 1 (Mfn1) and Mfn2 was significantly decreased. These data indicate that NSC transplantation may enhance mitochondria biogenesis and further rescue cognitive deficits in AD-like mice. PMID:25582749

Zhang, Wei; Gu, Guo-Jun; Shen, Xing; Zhang, Qi; Wang, Gang-Min; Wang, Pei-Jun

2015-03-01

62

Adiponectin Prevents Reduction of Lipid-Induced Mitochondrial Biogenesis via AMPK/ACC2 Pathway in Chicken Adipocyte.  

PubMed

Adiponectin (APN) stimulates mitochondrial biogenesis and reduces lipid content in human and animal adipocytes. However, the mechanism of adiponectin in regulating mitochondrial biogenesis in chicken adipocytes has never been reported. The objective of this study is to examine the mechanism that adiponectin plays in lipid-induced mitochondrial biogenesis and mitochondrial function in chicken adipocytes. We found that the overexpression of adiponectin reduced the membrane DAG content and elevated the membrane translocation of PKC?. In contrast to control groups, the overexpression of adiponectin increased mitochondrial density and mitochondrial DNA contents and peroxisome proliferator-activated receptor ?coactivator 1? (PGC1-?) expression. Mitochondrial membrane potential and cytochrome C (Cyt?C) content were detected by JC-1 fluorescent staining and immunofluorescence which indicated that overexpression of adiponectin enhanced mitochondrial ATP synthesis. Moreover, AMPK/ACC2 signaling pathway was activated along with the elevation of PGC1-? and TFAM by the overexpression of adiponectin, meanwhile the lipid transcription marker genes were down-regulated. This effect was alleviated by reducing adiponectin and a specific inhibitor of AMPK pathway. We concluded that adiponectin could prevent reduction of lipid-induced mitochondrial biogenesis via AMPK/ACC2 pathway in chicken adipocytes. J. Cell. Biochem. 116: 1090-1100, 2015. © 2014 Wiley Periodicals, Inc. PMID:25536013

Gan, Lu; Yan, Jun; Liu, Zhenjiang; Feng, Min; Sun, Chao

2015-06-01

63

Nrf2 promotes alveolar mitochondrial biogenesis and resolution of lung injury in Staphylococcus aureus pneumonia in mice  

PubMed Central

Acute lung injury (ALI) initiates protective responses involving genes downstream of the Nrf2 (Nfe2l2) transcription factor, including heme oxygenase-1 (HO-1), which stimulates mitochondrial biogenesis and related anti-inflammatory processes. We examined mitochondrial biogenesis during Staphylococcus aureus pneumonia in mice and the effect of Nrf2 deficiency on lung mitochondrial biogenesis and resolution of lung inflammation. S. aureus pneumonia established by nasal insufflation of live bacteria was studied in mitochondrial reporter (mt-COX8-GFP) mice, wild-type (WT) mice, and Nrf2?/? mice. Bronchoalveolar lavage, wet/dry ratios, real-time RT-PCR and Western analysis, immunohistochemistry, and fluorescence microscopy were performed on the lung at 0, 6, 24, and 48 h. The mice survived S. aureus inoculations at 5 × 108 CFU despite diffuse lung inflammation and edema, but the Nrf2?/? lung showed increased ALI. In mt-COX8-GFP mice, mitochondrial fluorescence was enhanced in bronchial and alveolar type II (AT2) epithelial cells. WT mice displayed rapid HO-1 upregulation and lower proinflammatory TNF-?, IL-1?, and CCL2 and, especially in AT2 cells, higher anti-inflammatory IL-10 and suppressor of cytokine signaling-3 than Nrf2?/? mice. In the alveolar region, WT but not Nrf2?/? mice showed strongly induced nuclear respiratory factor-1, PGC-1?, mitochondrial transcription factor-A, SOD2, Bnip3, mtDNA copy number, and citrate synthase. These findings indicate that S. aureus pneumonia induces Nrf2-dependent mitochondrial biogenesis in the alveolar region, mainly in AT2 cells. Absence of Nrf2 suppresses the alveolar transcriptional network for mitochondrial biogenesis and anti-inflammation, which worsens ALI. The findings link redox activation of mitochondrial biogenesis to ALI resolution. PMID:22940620

Athale, Janhavi; Ulrich, Allison; MacGarvey, Nancy Chou; Bartz, Raquel R.; Welty-Wolf, Karen E.; Suliman, Hagir B.; Piantadosi, Claude A.

2013-01-01

64

Developmental regulation of mitochondrial biogenesis and function in the mouse mammary gland during a prolonged lactation cycle  

Technology Transfer Automated Retrieval System (TEKTRAN)

The regulation of mitochondrial biogenesis and function in the lactating mammary cell is poorly understood. The goal of this study was to use proteomics to relate temporal changes in mammary cell mitochondrial function during lactation to changes in the proteins that make up this organelle. The hypo...

65

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1? expression.  

PubMed

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1? (PGC-1?) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10mg/kgb.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits-NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1? was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1? in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1? seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. PMID:24084166

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J L; Bal, Amanjit; Gill, Kiran Dip

2013-12-01

66

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats  

PubMed Central

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK. PMID:22808092

Jeong, Hyun Woo; Cho, Si Young; Kim, Shinae; Shin, Eui Seok; Kim, Jae Man; Song, Min Jeong; Park, Pil Joon; Sohn, Jong Hee; Park, Hyon; Seo, Dae-Bang; Kim, Wan Gi; Lee, Sang-Jun

2012-01-01

67

Chitooligosaccharide induces mitochondrial biogenesis and increases exercise endurance through the activation of Sirt1 and AMPK in rats.  

PubMed

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK. PMID:22808092

Jeong, Hyun Woo; Cho, Si Young; Kim, Shinae; Shin, Eui Seok; Kim, Jae Man; Song, Min Jeong; Park, Pil Joon; Sohn, Jong Hee; Park, Hyon; Seo, Dae-Bang; Kim, Wan Gi; Lee, Sang-Jun

2012-01-01

68

R -?-Lipoic acid and acetyl- l -carnitine complementarily promote mitochondrial biogenesis in murine 3T3-L1 adipocytes  

Microsoft Academic Search

Aims\\/hypothesis  The aim of the study was to address the importance of mitochondrial function in insulin resistance and type 2 diabetes, and\\u000a also to identify effective agents for ameliorating insulin resistance in type 2 diabetes. We examined the effect of two mitochondrial\\u000a nutrients, R-?-lipoic acid (LA) and acetyl-l-carnitine (ALC), as well as their combined effect, on mitochondrial biogenesis in 3T3-L1 adipocytes.

W. Shen; K. Liu; C. Tian; L. Yang; X. Li; J. Ren; L. Packer; C. W. Cotman; J. Liu

2008-01-01

69

Eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis  

PubMed Central

Lemon (Citrus limon) contains various bioactive flavonoids, and prevents obesity and obesity-associated metabolic diseases. We focused on eriocitrin (eriodictyol 7-rutinoside), a powerful antioxidative flavonoid in lemon with lipid-lowering effects in a rat model of high-fat diet. To investigate the mechanism of action of eriocitrin, we conducted feeding experiments on zebrafish with diet-induced obesity. Oral administration of eriocitrin (32?mg/kg/day for 28 days) improved dyslipidaemia and decreased lipid droplets in the liver. DNA microarray analysis revealed that eriocitrin increased mRNA of mitochondrial biogenesis genes, such as mitochondria transcription factor, nuclear respiratory factor 1, cytochrome c oxidase subunit 4, and ATP synthase. In HepG2 cells, eriocitrin also induced the corresponding orthologues, and reduced lipid accumulation under conditions of lipid loading. Eriocitrin increased mitochondrial size and mtDNA content, which resulted in ATP production in HepG2 cells and zebrafish. In summary, dietary eriocitrin ameliorates diet-induced hepatic steatosis with activation of mitochondrial biogenesis. PMID:24424211

Hiramitsu, Masanori; Shimada, Yasuhito; Kuroyanagi, Junya; Inoue, Takashi; Katagiri, Takao; Zang, Liqing; Nishimura, Yuhei; Nishimura, Norihiro; Tanaka, Toshio

2014-01-01

70

cGMP-Selective Phosphodiesterase Inhibitors Stimulate Mitochondrial Biogenesis and Promote Recovery from Acute Kidney Injury  

PubMed Central

Recent studies demonstrate that mitochondrial dysfunction is a mediator of acute kidney injury (AKI). Consequently, restoration of mitochondrial function after AKI may be key to the recovery of renal function. Mitochondrial function can be restored through the generation of new, functional mitochondria in a process called mitochondrial biogenesis (MB). Despite its potential therapeutic significance, very few pharmacological agents have been identified to induce MB. To examine the efficacy of phosphodiesterase (PDE) inhibitors (PDE3: cAMP and cGMP activity; and PDE4: cAMP activity) in stimulating MB, primary cultures of renal proximal tubular cells (RPTCs) were treated with a panel of inhibitors for 24 hours. PDE3, but not PDE4, inhibitors increased the FCCP-uncoupled oxygen consumption rate (OCR), a marker of MB. Exposure of RPTCs to the PDE3 inhibitors, cilostamide and trequinsin, for 24 hours increased peroxisome proliferator–activated receptor ? coactivator-1?, and multiple mitochondrial electron transport chain genes. Cilostamide and trequinsin also increased mRNA expression of mitochondrial genes and mitochondrial DNA copy number in mice renal cortex. Consistent with these experiments, 8-Br-cGMP increased FCCP-uncoupled OCR and mitochondrial gene expression, whereas 8-Br-cAMP had no effect. The cGMP-specific PDE5 inhibitor sildenafil also induced MB in RPTCs and in vivo in mouse renal cortex. Treatment of mice with sildenafil after folic acid–induced AKI promoted restoration of MB and renal recovery. These data provide strong evidence that specific PDE inhibitors that increase cGMP are inducers of MB in vitro and in vivo, and suggest their potential efficacy in AKI and other diseases characterized by mitochondrial dysfunction and suppressed MB. PMID:24042162

Whitaker, Ryan M.; Wills, Lauren P.; Stallons, L. Jay

2013-01-01

71

Aluminium induced oxidative stress results in decreased mitochondrial biogenesis via modulation of PGC-1? expression  

SciTech Connect

The present investigation was carried out to elucidate a possible molecular mechanism related to the effects of aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of Peroxisome proliferator activated receptor gamma co-activator 1? (PGC-1?) and its downstream targets i.e. Nuclear respiratory factor-1(NRF-1), Nuclear respiratory factor-2(NRF-2) and Mitochondrial transcription factor A (Tfam) in mitochondrial biogenesis. Aluminium lactate (10 mg/kg b.wt./day) was administered intragastrically to rats for 12 weeks. After 12 weeks of exposure, we found an increase in ROS levels, mitochondrial DNA oxidation and decrease in citrate synthase activity in the Hippocampus (HC) and Corpus striatum (CS) regions of rat brain. On the other hand, there was a decrease in the mRNA levels of the mitochondrial encoded subunits–NADH dehydrogenase (ND) subunits i.e. ND1, ND2, ND3, Cytochrome b (Cytb), Cytochrome oxidase (COX) subunits i.e. COX1, COX3, ATP synthase (ATPase) subunit 6 along with reduced expression of nuclear encoded subunits COX4, COX5A, COX5B of Electron transport chain (ETC). Besides, a decrease in mitochondrial DNA copy number and mitochondrial content in both regions of rat brain was observed. The PGC-1? was down-regulated in aluminium treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1? in aluminium treated rats. Electron microscopy results revealed a significant increase in the mitochondrial swelling, loss of cristae, chromatin condensation and decreases in mitochondrial number in case of aluminium treated rats as compared to control. So, PGC-1? seems to be a potent target for aluminium neurotoxicity, which makes it an almost ideal target to control or limit the damage that has been associated with the defective mitochondrial function seen in neurodegenerative diseases. - Highlights: • Aluminium decreases the mRNA levels of mitochondrial and nuclear encoded subunits. • It decreases the mtDNA copy number and mitochondrial content in rat brain. • It down-regulates the mRNA and protein levels of PGC-1?, NRF-1, NRF-2 and Tfam. • It also disturbs the mitochondrial or nuclear architecture of neurons. • Finally it also decreases mitochondrial number in HC and CS regions of rat brain.

Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Kandimalla, Ramesh J.L. [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012 (India); Bal, Amanjit [Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh (India); Gill, Kiran Dip, E-mail: kdgill2002@yahoo.co.in [Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh 160012 (India)

2013-12-01

72

Mitochondrial dynamics, biogenesis, and function are coordinated with the cell cycle by APC/C CDH1.  

PubMed

Cell proliferation is associated with a high rate of aerobic glycolysis, which has been widely interpreted as a compensatory mechanism for suppressed mitochondrial function, despite reports of high respiration rates. The molecular mechanisms that link cell proliferation with mitochondrial metabolism, dynamics, and biogenesis remain obscure. Here, we show that proliferation is associated with an increase in both glycolysis and respiration, in conjunction with mitochondrial fusion and biogenesis. Changes in mitochondrial morphology and mass are due to accumulation of OPA1, MFN1, and TFAM, silencing any of which hinders cell proliferation. Moreover, the levels of OPA1, MFN1, and TFAM are regulated by the ubiquitin ligase APC/C(CDH1), which also controls proteasomal degradation of key glycolytic, glutaminolytic, and cell-cycle proteins. Thus, we have identified an important component of the molecular mechanism that coordinates cell proliferation with activation of the mitochondrial metabolic machinery that provides the necessary energy and biosynthetic substrates. PMID:22482729

Garedew, Assegid; Andreassi, Catia; Moncada, Salvador

2012-04-01

73

C7orf30 is necessary for biogenesis of the large subunit of the mitochondrial ribosome  

PubMed Central

Defects of the translation apparatus in human mitochondria are known to cause disease, yet details of how protein synthesis is regulated in this organelle remain to be unveiled. Here, we characterize a novel human protein, C7orf30 that contributes critically to mitochondrial translation and specifically associates with the large subunit of the mitochondrial ribosome (mt-LSU). Inactivation of C7orf30 in human cells by RNA interference results in respiratory incompetence owing to reduced mitochondrial translation rates without any appreciable effects on the steady-state levels of mitochondrial mRNAs and rRNAs. Ineffective translation in C7orf30-depleted cells or cells overexpressing a dominant-negative mutant of the protein results from aberrant assembly of mt-LSU and consequently reduced formation of the monosome. These findings lead us to propose that C7orf30 is a human assembly and/or stability factor involved in the biogenesis of the large subunit of the mitochondrial ribosome. PMID:22238376

Rorbach, Joanna; Gammage, Payam A.; Minczuk, Michal

2012-01-01

74

Flavan-3-ol fraction from cocoa powder promotes mitochondrial biogenesis in skeletal muscle in mice  

PubMed Central

Background Numerous clinical studies have reported that ingestion of chocolate has reduced risk of metabolic syndrome. In order to elucidate the mechanism, we evaluated the influence of flavan-3-ols derived from cocoa powder on energy metabolism in mice using an indirect calorimetric method. Method The mice were divided into two groups, and administered either distilled water or 50 mg/kg of flavan-3-ol fraction for 2 weeks. At the end of the experimental period, animals were sacrificed after blood pressure and the mean respiratory exchange ratio (RER) over 24 hours were measured. Results The mean respiratory exchange ratio (RER) over 24 hours was reduced significantly in the flavan-3-ols group. The mean blood pressure was significantly decreased in flavan-3-ols treatment group compared with control group. The protein level of carnitine palmitoyltransferase 2 (CPT2) was increased significantly by flavan-3-ols in skeletal muscle, but not in liver. Uncoupling protein (UCP) 1 was increased significantly in brown adipose tissue by flavan-3-ols. The mitochondria copy number in gastrocnemius and soleus muscles and brown adipose tissue were increased significantly by administration of flavan-3-ol fraction. Conclusion These results suggest that flavan-3-ols enhances lipolysis and promotes mitochondrial biogenesis. We conclude that improvement of metabolic syndrome risk factors following ingestion of chocolate may be induced, in part, by the mitochondrial biogenesis-promoting effect of flavan-3-ols. PMID:24708519

2014-01-01

75

Metastasis suppressor KISS1 appears to reverse the Warburg effect by enhancing mitochondrial biogenesis  

PubMed Central

Cancer cells tend to utilize aerobic glycolysis even under normoxic conditions, commonly called the “Warburg Effect.” Aerobic glycolysis often directly correlates with malignancy, but its purpose, if any, in metastasis remains unclear. When wild-type KISS1 metastasis suppressor is expressed, aerobic glycolysis decreases and oxidative phosphorylation predominates. However, when KISS1 is missing the secretion signal peptide (?SS), invasion and metastasis are no longer suppressed and cells continue to metabolize using aerobic glycolysis. KISS1-expressing cells have 30–50% more mitochondrial mass than ?SS-expressing cells, which is accompanied by correspondingly increased mitochondrial gene expression and higher expression of PGC1?, a master co-activator that regulates mitochondrial mass and metabolism. PGC1?-mediated downstream pathways (i.e. fatty acid synthesis and ?-oxidation) are differentially regulated by KISS1, apparently reliant upon direct KISS1 interaction with NRF1, a major transcription factor involved in mitochondrial biogenesis. Since the downstream effects could be reversed using shRNA to KISS1 or PGC1?, these data appear to directly connect changes in mitochondria mass, cellular glucose metabolism and metastasis. PMID:24351292

Liu, Wen; Beck, Benjamin H.; Vaidya, Kedar S.; Nash, Kevin T.; Feeley, Kyle P.; Ballinger, Scott W.; Pounds, Keke M.; Denning, Warren L.; Diers, Anne R.; Landar, Aimee; Dhar, Animesh; Iwakuma, Tomoo; Welch, Danny R.

2014-01-01

76

Mammalian mitochondrial complex I: biogenesis, regulation, and reactive oxygen species generation.  

PubMed

Virtually every mammalian cell contains mitochondria. These double-membrane organelles continuously change shape and position and contain the complete metabolic machinery for the oxidative conversion of pyruvate, fatty acids, and amino acids into ATP. Mitochondria are crucially involved in cellular Ca2+ and redox homeostasis and apoptosis induction. Maintenance of mitochondrial function and integrity requires an inside-negative potential difference across the mitochondrial inner membrane. This potential is sustained by the electron-transport chain (ETC). NADH:ubiquinone oxidoreductase or complex I (CI), the first and largest protein complex of the ETC, couples the oxidation of NADH to the reduction of ubiquinone. During this process, electrons can escape from CI and react with ambient oxygen to produce superoxide and derived reactive oxygen species (ROS). Depending on the balance between their production and removal by antioxidant systems, ROS may function as signaling molecules or induce damage to a variety of biomolecules or both. The latter ultimately leads to a loss of mitochondrial and cellular function and integrity. In this review, we discuss (a) the role of CI in mitochondrial functioning; (b) the composition, structure, and biogenesis of CI; (c) regulation of CI function; (d) the role of CI in ROS generation; and (e) adaptive responses to CI deficiency. PMID:19803744

Koopman, Werner J H; Nijtmans, Leo G J; Dieteren, Cindy E J; Roestenberg, Peggy; Valsecchi, Federica; Smeitink, Jan A M; Willems, Peter H G M

2010-06-15

77

Massage therapy attenuates inflammatory signaling after exercise-induced muscle damage.  

PubMed

Massage therapy is commonly used during physical rehabilitation of skeletal muscle to ameliorate pain and promote recovery from injury. Although there is evidence that massage may relieve pain in injured muscle, how massage affects cellular function remains unknown. To assess the effects of massage, we administered either massage therapy or no treatment to separate quadriceps of 11 young male participants after exercise-induced muscle damage. Muscle biopsies were acquired from the quadriceps (vastus lateralis) at baseline, immediately after 10 min of massage treatment, and after a 2.5-hour period of recovery. We found that massage activated the mechanotransduction signaling pathways focal adhesion kinase (FAK) and extracellular signal-regulated kinase 1/2 (ERK1/2), potentiated mitochondrial biogenesis signaling [nuclear peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?)], and mitigated the rise in nuclear factor ?B (NF?B) (p65) nuclear accumulation caused by exercise-induced muscle trauma. Moreover, despite having no effect on muscle metabolites (glycogen, lactate), massage attenuated the production of the inflammatory cytokines tumor necrosis factor-? (TNF-?) and interleukin-6 (IL-6) and reduced heat shock protein 27 (HSP27) phosphorylation, thereby mitigating cellular stress resulting from myofiber injury. In summary, when administered to skeletal muscle that has been acutely damaged through exercise, massage therapy appears to be clinically beneficial by reducing inflammation and promoting mitochondrial biogenesis. PMID:22301554

Crane, Justin D; Ogborn, Daniel I; Cupido, Colleen; Melov, Simon; Hubbard, Alan; Bourgeois, Jacqueline M; Tarnopolsky, Mark A

2012-02-01

78

Gene expression of key regulators of mitochondrial biogenesis is sex dependent in mice with growth hormone receptor deletion in liver  

PubMed Central

Mitochondrial biogenesis is an essential process for cell viability. Mice with disruption of the growth hormone receptor (GHR) gene (Ghr gene) in the liver (LiGHRKO), in contrast to long-lived mice with global deletion of the Ghr gene (GHRKO), are characterized by lack of improved insulin sensitivity and severe hepatic steatosis. Tissue-specific disruption of the GHR in liver results in a mouse model with dramatically altered GH/IGF1 axis. We have previously shown increased levels of key regulators of mitochondrial biogenesis in insulin-sensitive GHRKO mice. The aim of the present study is to assess, using real-time PCR, the gene expression of key regulators of mitochondrial biogenesis (Pgc1?, Ampk, Sirt1, Nrf2 and Mfn2) and a marker of mitochondrial activity (CoxIV) in brains, kidneys and livers of male and female LiGHRKO and wild-type (WT) mice. There were significant differences between males and females. In the brain, expression of Pgc1?, Ampk, Sirt1, Nrf2 and Mfn2 was lower in pooled females compared to pooled males. In the kidneys, expression of Ampk and Sirt1 was also lower in female mice. In the liver, no differences between males and females were observed. Sexual dimorphism may play an important role in regulating the biogenesis of mitochondria. PMID:25855408

Zawada, Ilona; Masternak, Michal M.; List, Edward O.; Stout, Michael B.; Berryman, Darlene E.; Lewinski, Andrzej; Kopchick, John J.; Bartke, Andrzej; Karbownik-Lewinska, Malgorzata; Gesing, Adam

2015-01-01

79

Overexpression of UCP1 in tobacco induces mitochondrial biogenesis and amplifies a broad stress response  

PubMed Central

Background Uncoupling protein one (UCP1) is a mitochondrial inner membrane protein capable of uncoupling the electrochemical gradient from adenosine-5?-triphosphate (ATP) synthesis, dissipating energy as heat. UCP1 plays a central role in nonshivering thermogenesis in the brown adipose tissue (BAT) of hibernating animals and small rodents. A UCP1 ortholog also occurs in plants, and aside from its role in uncoupling respiration from ATP synthesis, thereby wasting energy, it plays a beneficial role in the plant response to several abiotic stresses, possibly by decreasing the production of reactive oxygen species (ROS) and regulating cellular redox homeostasis. However, the molecular mechanisms by which UCP1 is associated with stress tolerance remain unknown. Results Here, we report that the overexpression of UCP1 increases mitochondrial biogenesis, increases the uncoupled respiration of isolated mitochondria, and decreases cellular ATP concentration. We observed that the overexpression of UCP1 alters mitochondrial bioenergetics and modulates mitochondrial-nuclear communication, inducing the upregulation of hundreds of nuclear- and mitochondrial-encoded mitochondrial proteins. Electron microscopy analysis showed that these metabolic changes were associated with alterations in mitochondrial number, area and morphology. Surprisingly, UCP1 overexpression also induces the upregulation of hundreds of stress-responsive genes, including some involved in the antioxidant defense system, such as superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione-S-transferase (GST). As a consequence of the increased UCP1 activity and increased expression of oxidative stress-responsive genes, the UCP1-overexpressing plants showed reduced ROS accumulation. These beneficial metabolic effects may be responsible for the better performance of UCP1-overexpressing lines in low pH, high salt, high osmolarity, low temperature, and oxidative stress conditions. Conclusions Overexpression of UCP1 in the mitochondrial inner membrane induced increased uncoupling respiration, decreased ROS accumulation under abiotic stresses, and diminished cellular ATP content. These events may have triggered the expression of mitochondrial and stress-responsive genes in a coordinated manner. Because these metabolic alterations did not impair plant growth and development, UCP1 overexpression can potentially be used to create crops better adapted to abiotic stress conditions. PMID:24886177

2014-01-01

80

Dynamic mobilization of PGC-1? mediates mitochondrial biogenesis for the protection of RGC-5 cells by resveratrol during serum deprivation.  

PubMed

Mitochondrial dysfunction contributing to the pathogenesis of glaucomatous neurodegeneration has stimulated considerable interest recently. In this study, we explored the role of peroxisome proliferator activated receptor-? co-activator 1? (PGC-1?) in resveratrol-triggered mitochondrial biogenesis for preventing apoptosis in a retinal ganglion cell line RGC-5. Our results showed that serum deprivation induced cell apoptosis in a time-dependent manner. Applying resveratrol maintained the normal mitochondrial membrane potential, decreased the levels of both total and cleaved caspase-3, and inhibited the release of cytochrome c, which subsequently enhanced cell survival. Moreover, resveratrol stimulated mitochondrial biogenesis by increasing the absolute quantity of mitochondria as well as their DNA copies. Treatment with resveratrol promoted the protein expression of SIRT1, but not PGC-1?; instead, resveratrol facilitated PGC-1? translocation from the cytoplasm to the nucleus and up-regulated NRF1 and TFAM, which were blocked by nicotinamide. Collectively, we demonstrate that the SIRT1-dependent PGC-1? subcellular translocation following resveratrol application potentially attenuates serum deprivation-elicited RGC-5 cell death, thereby raising the possibility of mitigating glaucomatous retinopathy by enhancement of mitochondrial biogenesis. PMID:23525928

Chen, Shida; Fan, Qian; Li, Ang; Liao, Dongjiang; Ge, Jian; Laties, Alan M; Zhang, Xiulan

2013-07-01

81

The interplay between apoptosis, mitophagy and mitochondrial biogenesis induced by resveratrol can determine activated hepatic stellate cells death or survival.  

PubMed

Resveratrol has been the focus of numerous studies reporting opposite effects that depend on its concentration. The GRX is an activated hepatic stellate cells model used to study liver fibrosis development and resolution. We recently showed that GRX treatment with RSV (0.1-50 µM) for 24 h triggered dose-dependent pro-oxidant effects, resulting in cytotoxicity and cell damage only at the highest concentration. Here, we evaluated whether the pro-oxidant effect of resveratrol treatment is accompanied by alterations on the GRX mitochondrial metabolism, and whether the concomitantly autophagy/mitophagy induction can influence on cell death or survival. We demonstrated that all concentrations of resveratrol promoted an increase of GRX cell death signals, altering the mitochondrial dynamics and function. Cells treated with all resveratrol concentrations presented higher autophagy/mitophagy features, but only treatments with 1 and 10 µM of resveratrol-induced mitochondrial biogenesis. Since cell damage was higher and there was no mitochondrial biogenesis in GRX treated with 50 µM of resveratrol, we suggest that these cells failed to remove and replace all damaged mitochondria. In conclusion, the cytotoxic effect of resveratrol that effectively promotes cell death could be related to the interrelation between the concomitant induction of apoptosis, autophagy/mitophagy and mitochondrial biogenesis in GRX. PMID:25234614

Meira Martins, Leo A; Vieira, Moema Queiroz; Ilha, Mariana; de Vasconcelos, Mariana; Biehl, Henrique B; Lima, Daniela B; Schein, Vanessa; Barbé-Tuana, Florencia; Borojevic, Radovan; Guma, Fátima Costa Rodrigues

2015-03-01

82

AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1  

PubMed Central

Our previous work has shown that Akt3 is required for mitochondrial biogenesis in primary human endothelial cells (ECs) and in Akt3-null mice; Akt3 affects subcellular localization of peroxisome proliferator-activated receptor ? coactivator-1 (PGC-1?), the master regulator of mitochondrial biogenesis. The purpose of this study is to determine the mechanism by which Akt3 controls the subcellular distribution of PGC-1? and to explore the effect on mitochondrial biogenesis and turnover during angiogenesis. Here we use standard biochemical analyses and Akt3-knockdown strategies to show that Akt3 controls the stabilization of chromosome maintenance region-1 (CRM-1), the major nuclear export receptor. Site-directed mutagenesis and association analyses show that PGC-1? nuclear export is CRM-1 dependent. Akt3 knockdown and CRM-1 overexpression cause 3-fold reductions in PGC-1? target gene expression, compared to control levels. Akt3 inhibition causes autophagy, as measured by autophagosome formation, in a CRM-1-dependent, Akt1/mTOR-independent pathway. In vivo, Akt3-null and heterozygous mice show dose-dependent decreases in angiogenesis compared to wild-type littermates (?5- and 2.5-fold decreases, respectively), as assessed by Matrigel plug assays. This correlates with an ?1.5-fold decrease in mitochondrial Cox IV expression. Our studies suggest that Akt3 is a regulator of mitochondrial dynamics in the vasculature via regulation of CRM-1-dependent nuclear export.—Corum, D. G., Tsichlis, P. N., Muise-Helmericks, R. C. AKT3 controls mitochondrial biogenesis and autophagy via regulation of the major nuclear export protein CRM-1. PMID:24081905

Corum, Daniel G.; Tsichlis, Philip N.; Muise-Helmericks, Robin C.

2014-01-01

83

Sex differences in mitochondrial biogenesis determine neuronal death and survival in response to oxygen glucose deprivation and reoxygenation  

PubMed Central

Background Mitochondrial dysfunction has been linked to neuronal death and a wide array of neurodegenerative diseases. Previously, we have shown sex differences in mitochondria-mediated cell death pathways following hypoxia-ischemia. However, the role of mitochondrial biogenesis in hypoxic-ischemic brain injury between male vs. female has not been studied yet. Results Primary cerebellar granule neurons (CGNs), isolated from P7 male and female mice (CD-1) segregated based on visual inspection of sex, were exposed to 2 h of oxygen glucose deprivation (OGD) followed by 6–24 h of reoxygenation (Reox). Mitochondrial membrane potential (??m) and cellular ATP levels were reduced significantly in XX CGNs as compared to XY CGNs. Mitochondrial DNA (mtDNA) content was increased (>2-fold) at 2 h OGD in XY CGNs and remained increased up to 24 h of Reox compared to XX neurons and normoxia controls. The expression of mitochondrial transcription factor A (Tfam), the nuclear respiratory factor-1 (NRF-1) and the peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?), a master regulator of mitochondrial biogenesis, were up-regulated (2-fold, ***p?mitochondrial proteins HSP60 and COXIV were increased in XY neurons only. Supportively, a balanced stimulation of fusion (Mfn 1and Mfn 2) and fission (Fis 1 and Drp 1) genes and enhanced formation of donut-shaped mitochondria were observed in XY CGNs vs. XX neurons (**p?mitochondrial biogenesis and morphological changes in a sex-specific way, influencing neuronal injury/survival differently in both sexes. PMID:24410996

2014-01-01

84

Monitoring of neuronal loss in the hippocampus of A?-injected rat: autophagy, mitophagy, and mitochondrial biogenesis stand against apoptosis.  

PubMed

In the present study, we tried to answer the following questions: which kind of defense pathways are activated after A? insult? How defense systems react against noxious effects of A? and whether they are able to deal against apoptosis or not? So, we traced some molecular pathways including autophagy, mitophagy, and mitochondrial biogenesis before reaching to the endpoint of apoptosis. Besides, we measured the function of mitochondria after injection of A? (1-42) in CA1 area of hippocampus as a model of Alzheimer's disease (AD). Based on our data, autophagy markers reached to their maximum level and returned to the control level as apoptotic markers started to increase. As a specialized form of autophagy, mitophagy markers followed the trend of autophagy markers. Whereas mitochondrial dynamic processes shifted toward fission, mitochondrial biogenesis was severely affected by A? and significantly decreased. Alongside suppression of mitochondrial biogenesis, activity of specific enzymes involved in antioxidant defense system, electron transport chain, and tricarboxylic acid cycle (TCA) decreased in response to the A?. Activity of antioxidant enzymes increased at first and then decreased significantly compared to the control. TCA enzymes aconitase and malate dehydrogenase activities reduced immediately while citrate synthase and fumarase activities did not change. Based on our finding, monitoring of the master molecules of intracellular cascades and determining their trends before the destructive function of A? could be the target of therapeutic issues for AD. PMID:24203394

Shaerzadeh, Fatemeh; Motamedi, Fereshteh; Minai-Tehrani, Dariush; Khodagholi, Fariba

2014-03-01

85

Increased mitochondrial biogenesis preserves intestinal stem cell homeostasis and contributes to longevity in Indy mutant flies  

PubMed Central

The Drosophila Indy (I'm Not Dead Yet) gene encodes a plasma membrane transporter of Krebs cycle intermediates, with robust expression in tissues associated with metabolism. Reduced INDY alters metabolism and extends longevity in a manner similar to caloric restriction (CR); however, little is known about the tissue specific physiological effects of INDY reduction. Here we focused on the effects of INDY reduction in the Drosophila midgut due to the importance of intestinal tissue homeostasis in healthy aging and longevity. The expression of Indy mRNA in the midgut changes in response to aging and nutrition. Genetic reduction of Indy expression increases midgut expression of the mitochondrial regulator spargel/dPGC-1, which is accompanied by increased mitochondrial biogenesis and reduced reactive oxygen species (ROS). These physiological changes in the Indy mutant midgut preserve intestinal stem cell (ISC) homeostasis and are associated with healthy aging. Genetic studies confirm that dPGC-1 mediates the regulatory effects of INDY, as illustrated by lack of longevity extension and ISC homeostasis in flies with mutations in both Indy and dPGC1. Our data suggest INDY may be a physiological regulator that modulates intermediary metabolism in response to changes in nutrient availability and organismal needs by modulating dPGC-1 PMID:24827528

Rogers, Ryan P.; Rogina, Blanka

2014-01-01

86

Aging and Calorie Restriction Oppositely Affect Mitochondrial Biogenesis through TFAM Binding at Both Origins of Mitochondrial DNA Replication in Rat Liver  

PubMed Central

Aging affects mitochondria in a tissue-specific manner. Calorie restriction (CR) is, so far, the only intervention able to delay or prevent the onset of several age-related changes also in mitochondria. Using livers from middle age (18-month-old), 28-month-old and 32-month-old ad libitum-fed and 28-month-old calorie-restricted rats we found an age-related decrease in mitochondrial DNA (mtDNA) content and mitochondrial transcription factor A (TFAM) amount, fully prevented by CR. We revealed also an age-related decrease, completely prevented by CR, for the proteins PGC-1? NRF-1 and cytochrome c oxidase subunit IV, supporting the efficiency of CR to forestall the age-related decrease in mitochondrial biogenesis. Furthermore, CR counteracted the age-related increase in oxidative damage to proteins, represented by the increased amount of oxidized peroxiredoxins (PRX-SO3) in the ad libitum-fed animals. An unexpected age-related decrease in the mitochondrial proteins peroxiredoxin III (Prx III) and superoxide dismutase 2 (SOD2), usually induced by increased ROS and involved in mitochondrial biogenesis, suggested a prevailing relevance of the age-reduced mitochondrial biogenesis above the induction by ROS in the regulation of expression of these genes with aging. The partial prevention of the decrease in Prx III and SOD2 proteins by CR also supported the preservation of mitochondrial biogenesis in the anti-aging action of CR. To investigate further the age- and CR-related effects on mitochondrial biogenesis we analyzed the in vivo binding of TFAM to specific mtDNA regions and demonstrated a marked increase in the TFAM-bound amounts of mtDNA at both origins of replication with aging, fully prevented by CR. A novel, positive correlation between the paired amounts of TFAM-bound mtDNA at these sub-regions was found in the joined middle age ad libitum-fed and 28-month-old calorie-restricted groups, but not in the 28-month-old ad libitum-fed counterpart suggesting a quite different modulation of TFAM binding at both origins of replication in aging and CR. PMID:24058615

Picca, Anna; Pesce, Vito; Fracasso, Flavio; Joseph, Anna-Maria; Leeuwenburgh, Christiaan; Lezza, Angela M. S.

2013-01-01

87

Activation of Mitochondrial Biogenesis by Heme Oxygenase-1–mediated NF-E2–related Factor-2 Induction Rescues Mice from Lethal Staphylococcus aureus Sepsis  

PubMed Central

Rationale: Mitochondrial damage is an important component of multiple organ failure syndrome, a highly lethal complication of severe sepsis that lacks specific therapy. Mitochondrial quality control is regulated in part by the heme oxygenase-1 (HO-1; Hmox1) system through the redox-regulated NF-E2–related factor-2 (Nrf2) transcription factor, but its role in mitochondrial biogenesis in Staphylococcus aureus sepsis is unknown. Objectives: To test the hypothesis that Nrf2-dependent up-regulation of the HO-1/carbon monoxide (CO) system would preserve mitochondrial biogenesis and rescue mice from lethal S. aureus sepsis. Methods: A controlled murine S. aureus peritonitis model with and without inhaled CO was examined for HO-1 and Nrf2 regulation of mitochondrial biogenesis and the resolution of hepatic mitochondrial damage. Measurements and Main Results: Sepsis survival was significantly enhanced using inhaled CO (250 ppm once-daily for 1 h), and linked mechanistically to Hmox1 induction and mitochondrial HO activity through Nrf2 transcriptional and Akt kinase activity. HO-1/CO stimulated Nrf2-dependent gene expression and nuclear accumulation of nuclear respiratory factor-1, -2? (Gabpa), and peroxisome proliferator-activated receptor gamma coactivator-1?; increased mitochondrial transcription factor-A and citrate synthase protein levels; and augmented mtDNA copy number. CO enhanced antiinflammatory IL-10 and reduced proinflammatory tumor necrosis factor-? production. By contrast, Nrf2?/? and Akt1?/? mice lacked CO induction of Hmox1 and mitochondrial biogenesis, and CO rescued neither strain from S. aureus sepsis. Conclusions: We identify an inducible Nrf2/HO-1 regulatory cycle for mitochondrial biogenesis that is prosurvival and counter-inflammatory in sepsis, and describe targeted induction of mitochondrial biogenesis as a potential multiple organ failure therapy. PMID:22312014

MacGarvey, Nancy Chou; Suliman, Hagir B.; Bartz, Raquel R.; Fu, Ping; Withers, Crystal M.; Welty-Wolf, Karen E.

2012-01-01

88

Testosterone Plus Low-Intensity Physical Training in Late Life Improves Functional Performance, Skeletal Muscle Mitochondrial Biogenesis, and Mitochondrial Quality Control in Male Mice  

PubMed Central

Testosterone supplementation increases muscle mass in older men but has not been shown to consistently improve physical function and activity. It has been hypothesized that physical exercise is required to induce the adaptations necessary for translation of testosterone-induced muscle mass gain into functional improvements. However, the effects of testosterone plus low intensity physical exercise training (T/PT) on functional performance and bioenergetics are unknown. In this pilot study, we tested the hypothesis that combined administration of T/PT would improve functional performance and bioenergetics in male mice late in life more than low-intensity physical training alone. 28-month old male mice were randomized to receive T/PT or vehicle plus physical training (V/PT) for 2 months. Compare to V/PT control, administration of T/PT was associated with improvements in muscle mass, grip strength, spontaneous physical movements, and respiratory activity. These changes were correlated with increased mitochondrial DNA copy number and expression of markers for mitochondrial biogenesis. Mice receiving T/PT also displayed increased expression of key elements for mitochondrial quality control, including markers for mitochondrial fission-and-fusion and mitophagy. Concurrently, mice receiving T/PT also displayed increased expression of markers for reduced tissue oxidative damage and improved muscle quality. Conclusion: Testosterone administered with low-intensity physical training improves grip strength, spontaneous movements, and respiratory activity. These functional improvements were associated with increased muscle mitochondrial biogenesis and improved mitochondrial quality control. PMID:23240002

Guo, Wen; Wong, Siu; Li, Michelle; Liang, Wentao; Liesa, Marc; Serra, Carlo; Jasuja, Ravi; Bartke, Andrzej; Kirkland, James L.; Shirihai, Orian; Bhasin, Shalender

2012-01-01

89

MRM2 and MRM3 are involved in biogenesis of the large subunit of the mitochondrial ribosome  

PubMed Central

Defects of the translation apparatus in human mitochondria are known to cause disease, yet details of how protein synthesis is regulated in this organelle remain to be unveiled. Ribosome production in all organisms studied thus far entails a complex, multistep pathway involving a number of auxiliary factors. This includes several RNA processing and modification steps required for correct rRNA maturation. Little is known about the maturation of human mitochondrial 16S rRNA and its role in biogenesis of the mitoribosome. Here we investigate two methyltransferases, MRM2 (also known as RRMJ2, encoded by FTSJ2) and MRM3 (also known as RMTL1, encoded by RNMTL1), that are responsible for modification of nucleotides of the 16S rRNA A-loop, an essential component of the peptidyl transferase center. Our studies show that inactivation of MRM2 or MRM3 in human cells by RNA interference results in respiratory incompetence as a consequence of diminished mitochondrial translation. Ineffective translation in MRM2- and MRM3-depleted cells results from aberrant assembly of the large subunit of the mitochondrial ribosome (mt-LSU). Our findings show that MRM2 and MRM3 are human mitochondrial methyltransferases involved in the modification of 16S rRNA and are important factors for the biogenesis and function of the large subunit of the mitochondrial ribosome. PMID:25009282

Rorbach, Joanna; Boesch, Pierre; Gammage, Payam A.; Nicholls, Thomas J. J.; Pearce, Sarah F.; Patel, Dipali; Hauser, Andreas; Perocchi, Fabiana; Minczuk, Michal

2014-01-01

90

Enhanced oxidative stress and aberrant mitochondrial biogenesis in human neuroblastoma SH-SY5Y cells during methamphetamine induced apoptosis  

SciTech Connect

Methamphetamine (METH) is an abused drug that may cause psychiatric and neurotoxic damage, including degeneration of monoaminergic terminals and apoptosis of non-monoaminergic cells in Brain. The cellular and molecular mechanisms underlying these METH-induced neurotoxic effects remain to be clarified. In this study, we performed a time course assessment to investigate the effects of METH on intracellular oxidative stress and mitochondrial alterations in a human dopaminergic neuroblastoma SH-SY5Y cell line. We characterized that METH induces a temporal sequence of several cellular events including, firstly, a decrease in mitochondrial membrane potential within 1 h of the METH treatment, secondly, an extensive decline in mitochondrial membrane potential and increase in the level of reactive oxygen species (ROS) after 8 h of the treatment, thirdly, an increase in mitochondrial mass after the drug treatment for 24 h, and finally, a decrease in mtDNA copy number and mitochondrial proteins per mitochondrion as well as the occurrence of apoptosis after 48 h of the treatment. Importantly, vitamin E attenuated the METH-induced increases in intracellular ROS level and mitochondrial mass, and prevented METH-induced cell death. Our observations suggest that enhanced oxidative stress and aberrant mitochondrial biogenesis may play critical roles in METH-induced neurotoxic effects.

Wu, C.-W. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Ping, Y.-H. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Yen, J.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China); Brain Research Center, University System of Taiwan, Taiwan (China); Chang, C.-Y. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Wang, S.-F. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Yeh, C.-L. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Chi, C.-W. [Department a nd Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China); Department of Medical Research and Education, Taipei Veterans General Hospital, Taiwan 112 (China); Lee, H.-C. [Department and Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan 112 (China) and Department of Education and Research, Taipei City Hospital, Taipei, Taiwan (China) and Brain Research Center, University System of Taiwan, Taiwan (China)]. E-mail: hclee2@ym.edu.tw

2007-05-01

91

?-Lipoic acid treatment increases mitochondrial biogenesis and promotes beige adipose features in subcutaneous adipocytes from overweight/obese subjects.  

PubMed

?-Lipoic acid (?-Lip) is a natural occurring antioxidant with beneficial anti-obesity properties. The aim of this study was to investigate the putative effects of ?-Lip on mitochondrial biogenesis and the acquirement of brown-like characteristics by subcutaneous adipocytes from overweight/obese subjects. Thus, fully differentiated human subcutaneous adipocytes were treated with ?-Lip (100 and 250?M) for 24h for studies on mitochondrial content and morphology, mitochondrial DNA (mtDNA) copy number, fatty acid oxidation enzymes and brown/beige characteristic genes. The involvement of the Sirtuin1/Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (SIRT1/PGC-1?) pathway was also evaluated. Our results showed that ?-Lip increased mitochondrial content in cultured human adipocytes as revealed by electron microscopy and by mitotracker green labeling. Moreover, an enhancement in mtDNA content was observed. This increase was accompanied by an up-regulation of SIRT1 protein levels, a decrease in PGC-1? acetylation and up-regulation of Nuclear respiratory factor 1 (Nrf1) and Mitochondrial transcription factor (Tfam) transcription factors. Enhanced oxygen consumption and fatty acid oxidation enzymes, Carnitine palmitoyl transferase 1 and Acyl-coenzyme A oxidase (CPT-1 and ACOX) were also observed. Mitochondria from ?-Lip-treated adipocytes exhibited some morphological characteristics of brown mitochondria, and ?-Lip also induced up-regulation of some brown/beige adipocytes markers such as cell death-inducing DFFA-like effector a (Cidea) and T-box 1 (Tbx1). Moreover, ?-Lip up-regulated PR domain containing 16 (Prdm16) mRNA levels in treated adipocytes. Therefore, our study suggests the ability of ?-Lip to promote mitochondrial biogenesis and brown-like remodeling in cultured white subcutaneous adipocytes from overweight/obese donors. PMID:25542506

Fernández-Galilea, Marta; Pérez-Matute, Patricia; Prieto-Hontoria, Pedro L; Houssier, Marianne; Burrell, María A; Langin, Dominique; Martínez, J Alfredo; Moreno-Aliaga, María J

2015-03-01

92

SOD2 Deficient Erythroid Cells Up-Regulate Transferrin Receptor and Down-Regulate Mitochondrial Biogenesis and Metabolism  

PubMed Central

Background Mice irradiated and reconstituted with hematopoietic cells lacking manganese superoxide dismutase (SOD2) show a persistent hemolytic anemia similar to human sideroblastic anemia (SA), including characteristic intra-mitochondrial iron deposition. SA is primarily an acquired, clonal marrow disorder occurring in individuals over 60 years of age with uncertain etiology. Methodology/Principal Findings To define early events in the pathogenesis of this murine model of SA, we compared erythroid differentiation of Sod2-/- and normal bone marrow cells using flow cytometry and gene expression profiling of erythroblasts. The predominant transcriptional differences observed include widespread down-regulation of mitochondrial metabolic pathways and mitochondrial biogenesis. Multiple nuclear encoded subunits of complexes I-IV of the electron transport chain, ATP synthase (complex V), TCA cycle and mitochondrial ribosomal proteins were coordinately down-regulated in Sod2-/- erythroblasts. Despite iron accumulation within mitochondria, we found increased expression of transferrin receptor, Tfrc, at both the transcript and protein level in SOD2 deficient cells, suggesting deregulation of iron delivery. Interestingly, there was decreased expression of ABCb7, the gene responsible for X-linked hereditary SA with ataxia, a component required for iron-sulfur cluster biogenesis. Conclusions/Significance These results indicate that in erythroblasts, mitochondrial oxidative stress reduces expression of multiple nuclear genes encoding components of the respiratory chain, TCA cycle and mitochondrial protein synthesis. An additional target of particular relevance for SA is iron:sulfur cluster biosynthesis. By decreasing transcription of components of cluster synthesis machinery, both iron utilization and regulation of iron uptake are impacted, contributing to the sideroblastic phenotype. PMID:21326867

Martin, Florent M.; Xu, Xiuling; von Löhneysen, Katharina; Gilmartin, Timothy J.; Friedman, Jeffrey S.

2011-01-01

93

Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression.  

PubMed

Bioactive compounds reported to stimulate mitochondrial biogenesis are linked to many health benefits such increased longevity, improved energy utilization, and protection from reactive oxygen species. Previously studies have shown that mice and rats fed diets lacking in pyrroloquinoline quinone (PQQ) have reduced mitochondrial content. Therefore, we hypothesized that PQQ can induce mitochondrial biogenesis in mouse hepatocytes. Exposure of mouse Hepa1-6 cells to 10-30 microm PQQ for 24-48 h resulted in increased citrate synthase and cytochrome c oxidase activity, Mitotracker staining, mitochondrial DNA content, and cellular oxygen respiration. The induction of this process occurred through the activation of cAMP response element-binding protein (CREB) and peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a pathway known to regulate mitochondrial biogenesis. PQQ exposure stimulated phosphorylation of CREB at serine 133, activated the promoter of PGC-1alpha, and increased PGC-1alpha mRNA and protein expression. PQQ did not stimulate mitochondrial biogenesis after small interfering RNA-mediated reduction in either PGC-1alpha or CREB expression. Consistent with activation of the PGC-1alpha pathway, PQQ increased nuclear respiratory factor activation (NRF-1 and NRF-2) and Tfam, TFB1M, and TFB2M mRNA expression. Moreover, PQQ protected cells from mitochondrial inhibition by rotenone, 3-nitropropionic acid, antimycin A, and sodium azide. The ability of PQQ to stimulate mitochondrial biogenesis accounts in part for action of this compound and suggests that PQQ may be beneficial in diseases associated with mitochondrial dysfunction. PMID:19861415

Chowanadisai, Winyoo; Bauerly, Kathryn A; Tchaparian, Eskouhie; Wong, Alice; Cortopassi, Gino A; Rucker, Robert B

2010-01-01

94

The neurogenic basic helix-loop-helix transcription factor NeuroD6 enhances mitochondrial biogenesis and bioenergetics to confer tolerance of neuronal PC12-NeuroD6 cells to the mitochondrial stressor rotenone  

SciTech Connect

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial biogenesis and bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. -- Highlights: Black-Right-Pointing-Pointer NeuroD6 induces mitochondrial biogenesis in neuroprogenitor-like cells. Black-Right-Pointing-Pointer NeuroD6 augments the bioenergetic reserve of the neuronal PC12-NeuroD6 cells. Black-Right-Pointing-Pointer NeuroD6 increases the mitochondrial membrane potential and ATP levels. Black-Right-Pointing-Pointer NeuroD6 confers tolerance to rotenone via an adaptive mitochondrial response.

Baxter, Kristin Kathleen; Uittenbogaard, Martine [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States); Chiaramello, Anne, E-mail: achiaram@gwu.edu [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)] [Department of Anatomy and Regenerative Biology, George Washington University Medical Center, Washington, DC (United States)

2012-10-15

95

Promise of neurorestoration and mitochondrial biogenesis in Parkinson's disease with multi target drugs: an alternative to stem cell therapy.  

PubMed

There is an unmet need in progressive neurodegenerative diseases such as Parkinson's and Alzheimer's diseases. The present therapeutics for these diseases at best is symptomatic and is not able to delay disease or possess disease modifying activity. Thus an approach to drug design should be made to slow or halt progressive course of a neurological disorder by interfering with a disease-specific pathogenetic process. This would entail the ability of the drug to protect neurons by blocking the common pathway for neuronal injury and cell death and the ability to promote regeneration of neurons and restoration of neuronal function. We have now developed a number of multi target drugs which possess neuroprotective, and neurorestorative activity as well as being able to active PGC-1? (peroxisome proliferator-activated receptor ? coactivator-1?), SIRT1 (NAD-dependent deacetylase protein) and NTF (mitochondrial transcription factor) that are intimately associated with mitochondrial biogenesis. PMID:24167412

Youdim, Moussa Bh; Oh, Young J

2013-09-01

96

High fat diet-induced liver steatosis promotes an increase in liver mitochondrial biogenesis in response to hypoxia  

PubMed Central

Abstract Mitochondrial DNA (mtDNA) copy number plays a key role in the pathophysiology of metabolic syndrome-related phenotypes, but its role in non-alcoholic fatty liver disease (NAFLD) is not well understood. We evaluated the molecular mechanisms that may be involved in the regulation of liver mtDNA content in a high-fat-induced rat model of NAFLD. In particular, we tested the hypothesis that liver mtDNA copy number is associated with liver expression of HIF-1?. Rats were given either standard chow diet (SCD, n= 10) or high-fat diet (HFD, n= 15) for 20 weeks. Subsequently, mtDNA quantification using nuclear DNA (nDNA) as a reference was carried out using real time quantitative PCR. HFD induced a significant increase in liver mtDNA/nDNA ratio, which significantly correlated with the liver triglyceride content (R: 0.29, P < 0.05). The liver mtDNA/nDNA ratio significantly correlated with the hepatic expression of HIF-1? mRNA (R: 0.37, P < 0.001); liver HIF-1? mRNA was significantly higher in the HFD group. In addition, liver cytochrome c oxidase subunit IV isoform 1 (COX4I1) mRNA expression was also positively correlated with liver mtDNA content. The hepatic expression of mRNA of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor gamma coactivator-1? (PGC-1?) and PGC-1?, nuclear respiratory factor-1 (NRF-1), peroxisome proliferator-activated receptor ? and Tfam, was not associated with the liver mtDNA content. Neither hepatocyte apoptosis nor oxidative stress was involved in the HIF-1?-mediated increase in mtDNA copy number. In conclusion, we found that HFD promotes an increase in liver mitochondrial biogenesis in response to hypoxia via HIF-1?, probably to enhance the mitochondrial function as well as to accommodate the metabolic load. PMID:20629985

Carabelli, Julieta; Burgueño, Adriana L; Rosselli, Maria Soledad; Gianotti, Tomas Fernández; Lago, Nestor R; Pirola, Carlos J; Sookoian, Silvia

2011-01-01

97

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA)  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer We investigated mechanisms of mitochondrial regulation in rat hepatocytes. Black-Right-Pointing-Pointer Tetradecylthioacetic acid (TTA) was employed to activate mitochondrial oxidation. Black-Right-Pointing-Pointer Mitochondrial biogenesis and respiration were induced. Black-Right-Pointing-Pointer It was confirmed that PPAR target genes were induced. Black-Right-Pointing-Pointer The mechanism involved activation mTOR. -- Abstract: The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR{alpha}-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR.

Hagland, Hanne R.; Nilsson, Linn I.H. [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Burri, Lena [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway)] [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Nikolaisen, Julie [Department of Biomedicine, University of Bergen (Norway)] [Department of Biomedicine, University of Bergen (Norway); Berge, Rolf K. [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway) [Institute of Medicine, University of Bergen, Haukeland University Hospital (Norway); Department of Heart Disease, Haukeland University Hospital (Norway); Tronstad, Karl J., E-mail: karl.tronstad@biomed.uib.no [Department of Biomedicine, University of Bergen (Norway)

2013-01-11

98

Exercise-Induced Neuroprotection of Hippocampus in APP/PS1 Transgenic Mice via Upregulation of Mitochondrial 8-Oxoguanine DNA Glycosylase  

PubMed Central

Improving mitochondrial function has been proposed as a reasonable therapeutic strategy to reduce amyloid-? (A?) load and to modify the progression of Alzheimer's disease (AD). However, the relationship between mitochondrial adaptation and brain neuroprotection caused by physical exercise in AD is poorly understood. This study was undertaken to investigate the effects of long-term treadmill exercise on mitochondrial 8-oxoguanine DNA glycosylase-1 (OGG1) level, mtDNA oxidative damage, and mitochondrial function in the hippocampus of APP/PS1 transgenic mouse model of AD. In the present study, twenty weeks of treadmill training significantly improved the cognitive function and reduced the expression of A?-42 in APP/PS1 transgenic (Tg) mice. Training also ameliorated mitochondrial respiratory function by increasing the complexes I, and IV and ATP synthase activities, whereas it attenuated ROS generation and mtDNA oxidative damage in Tg mice. Furthermore, the impaired mitochondrial antioxidant enzymes and mitochondrial OGG1 activities seen in Tg mice were restored with training. Acetylation level of mitochondrial OGG1 and MnSOD was markedly suppressed in Tg mice after exercise training, in parallel with increased level of SIRT3. These findings suggest that exercise training could increase mtDNA repair capacity in the mouse hippocampus, which in turn would result in protection against AD-related mitochondrial dysfunction and phenotypic deterioration. PMID:25538817

Kang, Weimin; Jiang, Ning; Wang, Xun; Zhang, Yong; Ji, Li Li

2014-01-01

99

Biogenesis of giant mitochondria during insect flight muscle development in the locust, Locusta migratoria (L.). Transcription, translation and copy number of mitochondrial DNA.  

PubMed

The biogenesis of giant mitochondria in flight muscle of Locusta migratoria (L.) was analyzed at the molecular level. During the 2 weeks between the beginning of the last larval stage and the imago capable of sustained flight, individual mitochondria have been shown to enlarge 30-fold and the fractional mitochondrial volume of muscle cells increases fourfold [Brosemer, R.W., Vogell, W. and Bücher, Th. (1963) Biochem. Z. 338, 854-910]. Within the same period, the activity of cytochrome c oxidase, containing subunits encoded on mitochondrial DNA, increased twofold. However, no significant change in mitochondrial DNA copy number, and even a threefold decrease in mitochondrial transcripts, was observed. Mitochondrial translation rate, measured in isolated organelles, was twofold higher in larval muscle, which can be explained only partly by the higher content of mitochondrial RNAs. Thus, rather unusually, in this system of mitochondrial differentiation, the mitochondrial biosynthetic capacity correlates with the rate of organelle biogenesis rather than the steady-state concentration of a marker enzyme. The copy number of mitochondrial DNA does not seem to play a major role in determining either mitochondrial transcript levels or functional mass. PMID:10601845

Sogl, B; Gellissen, G; Wiesner, R J

2000-01-01

100

[Exercise-induced bronchoconstriction].  

PubMed

Terms exercise-induced asthma (EIA) or exercise-induced bronchoconstriction (EIB) are used to describe transient bronchoconstriction occurring during or immediately after vigorous exercise in some subjects. For the diagnosis of EIB it is necessary to show at least 10% decrease in FEV1 from baseline following physical exercise. The prevalence of EIB has been reported to be 12-15% in general population, 10-20% in summer olympic athletes, affecting up to 50-70% of winter athletes (particularly ski runners and skaters). There are two key theories explaining EIB: thermal and osmotic. Differential diagnosis of EIB should include chronic cardio-pulmonary diseases, vocal cord dysfunction, hyperventilation syndrome and poor physical fitness or overtraining. According to the ATS guidelines from 1999 for the diagnosis of EIB a standardized exercise on a treadmill or cycle ergometer test with stable environmental conditions regarding temperature and humidity of inhaled air, should be employed. Other laboratory tests assessing bronchial hyperresponsiveness to indirect stimuli including eucapnic voluntary hyperpnea (EVH), mannitol, hypertonic saline, AMP or measurement of exhaled nitric oxide (FENO) are also successfully used. In the prevention of EIB include both pharmacologic and non-pharmacologic treatment. In patients with poorly controlled asthma intensification of anti-inflammatory treatment can decrease the frequency and severity of EIB. Short and long acting beta2-agonists, antileukotriene drugs can be used prior to exercise to prevent EIB. PMID:21190152

Hildebrand, Katarzyna

2011-01-01

101

Transcription factor GABP\\/NRF-2 controlling biogenesis of mitochondria regulates basal expression of peroxiredoxin V but the mitochondrial function of peroxiredoxin V is dispensable in the dog  

Microsoft Academic Search

Peroxiredoxins (PRDXs) represent a conserved family of six antioxidant proteins which are widely expressed in different organisms. Human PRDX5 is detected in the cytosol and nucleus and can also target peroxisomes and mitochondria. However, it remains unknown if mitochondrial localization of PRDX5 is essential for its functions. Here we studied whether the known regulator of mitochondrial biogenesis, transcription factor GABP\\/NRF-2,

Nadezhda Usmanova; Nikolai Tomilin; Boris Zhivotovsky; Andrey Kropotov

2011-01-01

102

Mitochondrial Gene Therapy Improves Respiration, Biogenesis, and Transcription in G11778A Leber's Hereditary Optic Neuropathy and T8993G Leigh's Syndrome Cells  

PubMed Central

Abstract Many incurable mitochondrial disorders result from mutant mitochondrial DNA (mtDNA) and impaired respiration. Leigh's syndrome (LS) is a fatal neurodegenerative disorder of infants, and Leber's hereditary optic neuropathy (LHON) causes blindness in young adults. Treatment of LHON and LS cells harboring G11778A and T8993G mutant mtDNA, respectively, by >90%, with healthy donor mtDNA complexed with recombinant human mitochondrial transcription factor A (rhTFAM), improved mitochondrial respiration by ?1.2-fold in LHON cells and restored >50% ATP synthase function in LS cells. Mitochondrial replication, transcription, and translation of key respiratory genes and proteins were increased in the short term. Increased NRF1, TFAMB1, and TFAMA expression alluded to the activation of mitochondrial biogenesis as a mechanism for improving mitochondrial respiration. These results represent the development of a therapeutic approach for LHON and LS patients in the near future. PMID:22390282

Bergquist, Kristen; Young, Kisha; Gnaiger, Erich; Rao, Raj R.

2012-01-01

103

Induction of mitochondrial biogenesis and respiration is associated with mTOR regulation in hepatocytes of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA).  

PubMed

The hypolipidemic effect of peroxisome proliferator-activated receptor (PPAR) activators has been explained by increasing mitochondrial fatty acid oxidation, as observed in livers of rats treated with the pan-PPAR activator tetradecylthioacetic acid (TTA). PPAR-activation does, however, not fully explain the metabolic adaptations observed in hepatocytes after treatment with TTA. We therefore characterized the mitochondrial effects, and linked this to signalling by the metabolic sensor, the mammalian target of rapamycin (mTOR). In hepatocytes isolated from TTA-treated rats, the changes in cellular content and morphology were consistent with hypertrophy. This was associated with induction of multiple mitochondrial biomarkers, including mitochondrial DNA, citrate synthase and mRNAs of mitochondrial proteins. Transcription analysis further confirmed activation of PPAR?-associated genes, in addition to genes related to mitochondrial biogenesis and function. Analysis of mitochondrial respiration revealed that the capacity of both electron transport and oxidative phosphorylation were increased. These effects coincided with activation of the stress related factor, ERK1/2, and mTOR. The protein level and phosphorylation of the downstream mTOR actors eIF4G and 4E-BP1 were induced. In summary, TTA increases mitochondrial respiration by inducing hypertrophy and mitochondrial biogenesis in rat hepatocytes, via adaptive regulation of PPARs as well as mTOR. PMID:23228666

Hagland, Hanne R; Nilsson, Linn I H; Burri, Lena; Nikolaisen, Julie; Berge, Rolf K; Tronstad, Karl J

2013-01-11

104

The Neurogenic Basic Helix-Loop-Helix Transcription Factor NeuroD6 Enhances Mitochondrial Biogenesis and Bioenergetics to Confer Tolerance of Neuronal PC12-NeuroD6 Cells to the Mitochondrial Stressor Rotenone  

PubMed Central

The fundamental question of how and which neuronal specific transcription factors tailor mitochondrial bioenergetics to the need of developing neuronal cells has remained largely unexplored. In this study, we report that the neurogenic basic helix-loop-helix transcription factor NeuroD6 possesses mitochondrial biogenic properties by amplifying the mitochondrial DNA content and TFAM expression levels, a key regulator for mitochondrial biogenesis. NeuroD6-mediated increase in mitochondrial biogenesis in the neuronal progenitor-like PC12-NEUROD6 cells is concomitant with enhanced mitochondrial bioenergetic functions, including increased expression levels of specific subunits of respiratory complexes of the electron transport chain, elevated mitochondrial membrane potential and ATP levels produced by oxidative phosphorylation. Thus, NeuroD6 augments the bioenergetic capacity of PC12-NEUROD6 cells to generate an energetic reserve, which confers tolerance to the mitochondrial stressor, rotenone. We found that NeuroD6 induces an adaptive bioenergetic response throughout rotenone treatment involving maintenance of the mitochondrial membrane potential and ATP levels in conjunction with preservation of the actin network. In conclusion, our results support the concept that NeuroD6 plays an integrative role in regulating and coordinating the onset of neuronal differentiation with acquisition of adequate mitochondrial mass and energetic capacity to ensure energy demanding events, such as cytoskeletal remodeling, plasmalemmal expansion, and growth cone formation. PMID:22814253

Baxter, Kristin Kathleen; Uittenbogaard, Martine; Chiaramello, Anne

2012-01-01

105

Inhibition of akt phosphorylation diminishes mitochondrial biogenesis regulators, tricarboxylic acid cycle activity and exacerbates recognition memory deficit in rat model of Alzheimer's disease.  

PubMed

3-Methyladenine (3-MA), as a PI3K inhibitor, is widely used for inhibition of autophagy. Inhibition of PI3K class I leads to inhibition of Akt phosphorylation, a central molecule involved in diverse arrays of intracellular cascades in nervous system. Accordingly, in the present study, we aimed to determine the alterations of specific mitochondrial biogenesis markers and mitochondrial function in 3-MA-injected rats following amyloid beta (A?) insult. Our data revealed that inhibition of Akt phosphorylation downregulates master regulator of mitochondrial biogenesis, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1?). Our data also showed that decrease in PGC-1? level presumably is due to decrease in the phosphorylation of cAMP-response element binding and AMP-activated kinase, two upstream activators of PGC-1?. As a consequence, the level of some mitochondrial biogenesis factors including nuclear respiratory factor-1, mitochondrial transcription factor A, and Cytochrome c decreased significantly. Also, activities of tricarboxylic acid cycle (TCA) enzymes such as Aconitase, a-ketoglutarate dehydrogenase, and malate dehydrogenase reduced in the presence of 3-MA with or without A? insult. Decrease in mitochondrial biogenesis factors and TCA enzyme activity in the rats receiving 3-MA and A? were more compared to the rats that received either alone; indicating the additive destructive effects of these two agents. In agreement with our molecular results, data obtained from behavioral test (using novel objective recognition test) indicated that inhibition of Akt phosphorylation with or without A? injection impaired novel recognition (non-spatial) memory. Our results suggest that 3-MA amplified deleterious effects of A? by targeting central molecule Akt. PMID:25135709

Shaerzadeh, Fatemeh; Motamedi, Fereshteh; Khodagholi, Fariba

2014-11-01

106

Biogenesis of mitochondria: the mitochondrial gene (aap1) coding for mitochondrial ATPase subunit 8 in Saccharomyces cerevisiae.  

PubMed Central

A mitochondrial gene (denoted aap1) in Saccharomyces cerevisiae has been characterized by nucleotide sequence analysis of a region of mtDNA between the oxi3 and oli2 genes. The reading frame of the aap1 gene specifies a hydrophobic polypeptide containing 48 amino acids. The functional nature of this reading frame was established by sequence analysis of a series of mit- mutants and revertants. Evidence is presented that the aap1 gene codes for a mitochondrially synthesized polypeptide associated with the mitochondrial ATPase complex. This polypeptide (denoted subunit 8) is a proteolipid whose size has been previously assumed to be 10 kilodaltons based on its mobility on SDS-polyacrylamide gels, but the sequence of the aap1 gene predicts a molecular weight of 5,815 for this protein. PMID:6223276

Macreadie, I G; Novitski, C E; Maxwell, R J; John, U; Ooi, B G; McMullen, G L; Lukins, H B; Linnane, A W; Nagley, P

1983-01-01

107

Chromosomal localization of mitochondrial transcription factor A (TCF6), single-stranded DNA-binding protein (SSBP), and endonuclease G (ENDOG), three human housekeeping genes involving in mitochondrial biogenesis  

SciTech Connect

By using a PCR-based screening of a somatic cell hybrid panel and FISH, we have assigned the loci of mitochondrial single-stranded DNA-binding protein (SSBP), mitochondrial transcription factor A (TCF6), and mitochondrial endonuclease G (ENDOG) genes to human chromosomes 7q34, 10q21, and 9q34.1, respectively. The products of these three genes are involved in fundamental aspects of mitochondrial biogenesis, such as replication and transcription of the mitochondrial genome. The chromosomal localization of these genes is important to testing whether the corresponding proteins may play a role in the etiopathogenesis of human disorders associated with qualitative or quantitative abnormalities of mitochondrial DNA. 20 refs., 1 fig., 2 tabs.

Tiranti, V.; Rossi, G.; DiDonato, S. [Istituto Nazionale Neurologico, Carlo Besta (Italy)] [and others] [Istituto Nazionale Neurologico, Carlo Besta (Italy); and others

1995-01-20

108

Genomic and non-genomic regulation of PGC1 isoforms by estrogen to increase cerebral vascular mitochondrial biogenesis and reactive oxygen species protection.  

PubMed

We previously found that estrogen exerts a novel protective effect on mitochondria in brain vasculature. Here we demonstrate in rat cerebral blood vessels that 17?-estradiol (estrogen), both in vivo and ex vivo, affects key transcriptional coactivators responsible for mitochondrial regulation. Treatment of ovariectomized rats with estrogen in vivo lowered mRNA levels of peroxisome proliferator-activated receptor-? coactivator-1 alpha (PGC-1?) but increased levels of the other PGC-1 isoforms: PGC-1? and PGC-1 related coactivator (PRC). In vessels ex vivo, estrogen decreased protein levels of PGC-1? via activation of phosphatidylinositol 3-kinase (PI3K). Estrogen treatment also increased phosphorylation of forkhead transcription factor, FoxO1, a known pathway for PGC-1? downregulation. In contrast to the decrease in PGC-1?, estrogen increased protein levels of nuclear respiratory factor 1, a known PGC target and mediator of mitochondrial biogenesis. The latter effect of estrogen was independent of PI3K, suggesting a separate mechanism consistent with increased expression of PGC-1? and PRC. We demonstrated increased mitochondrial biogenesis following estrogen treatment in vivo; cerebrovascular levels of mitochondrial transcription factor A and electron transport chain subunits as well as the mitochondrial/nuclear DNA ratio were increased. We examined a downstream target of PGC-1?, glutamate-cysteine ligase (GCL), the rate-limiting enzyme for glutathione synthesis. In vivo estrogen increased protein levels of both GCL subunits and total glutathione levels. Together these data show estrogen differentially regulates PGC-1 isoforms in brain vasculature, underscoring the importance of these coactivators in adapting mitochondria in specific tissues. By upregulating PGC-1? and/or PRC, estrogen appears to enhance mitochondrial biogenesis, function and reactive oxygen species protection. PMID:24275351

Kemper, Martin F; Stirone, Chris; Krause, Diana N; Duckles, Sue P; Procaccio, Vincent

2014-01-15

109

Vitamin E and vitamin C increase mitochondrial biogenesis but inhibit mitochondrial protein expression in exercising obese rats  

Technology Transfer Automated Retrieval System (TEKTRAN)

Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial (MT) function and induces insulin resistance ...

110

Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats  

PubMed Central

Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-? (AS-?) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-? coactivator (PGC)-1?, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-?, ND3, COX-IV, mtDNA copy number, PGC-1? mRNA and protein, decreased acetylated PGC-1?, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate CsA-induced kidney injury, at least in part, through the stimulation of MB. PMID:23755172

Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi

2013-01-01

111

Biogenesis of the preprotein translocase of the outer mitochondrial membrane: protein kinase A phosphorylates the precursor of Tom40 and impairs its import  

PubMed Central

The preprotein translocase of the outer mitochondrial membrane (TOM) functions as the main entry gate for the import of nuclear-encoded proteins into mitochondria. The major subunits of the TOM complex are the three receptors Tom20, Tom22, and Tom70 and the central channel-forming protein Tom40. Cytosolic kinases have been shown to regulate the biogenesis and activity of the Tom receptors. Casein kinase 2 stimulates the biogenesis of Tom22 and Tom20, whereas protein kinase A (PKA) impairs the receptor function of Tom70. Here we report that PKA exerts an inhibitory effect on the biogenesis of the ?-barrel protein Tom40. Tom40 is synthesized as precursor on cytosolic ribosomes and subsequently imported into mitochondria. We show that PKA phosphorylates the precursor of Tom40. The phosphorylated Tom40 precursor is impaired in import into mitochondria, whereas the nonphosphorylated precursor is efficiently imported. We conclude that PKA plays a dual role in the regulation of the TOM complex. Phosphorylation by PKA not only impairs the receptor activity of Tom70, but it also inhibits the biogenesis of the channel protein Tom40. PMID:22419819

Rao, Sanjana; Schmidt, Oliver; Harbauer, Angelika B.; Schönfisch, Birgit; Guiard, Bernard; Pfanner, Nikolaus; Meisinger, Chris

2012-01-01

112

Adolescents and Exercise Induced Asthma  

ERIC Educational Resources Information Center

This article defines asthma and exercise induced asthma, and provides information on the triggers, signs, and symptoms of an attack. It also gives treatments for these conditions, along with prevention guidelines on how to handle an attack in the classroom or on the practice field. (Contains 2 tables and 1 figure.)

Hansen, Pamela; Bickanse, Shanna; Bogenreif, Mike; VanSickle, Kyle

2008-01-01

113

Conjugated Linoleic Acid (CLA) Stimulates Mitochondrial Biogenesis Signaling by the Upregulation of PPAR? Coactivator 1? (PGC-1?) in C2C12 Cells.  

PubMed

Along with its effect on body fat reduction, dietary conjugated linoleic acid (CLA) has been reported to improve physical activity and endurance capacity in mice. It has been suggested these effects may in part be due to physiological changes in skeletal muscle, however, the mode of action is not completely understood. Thus, the purpose of this study was to determine the relevant mechanisms of CLA isomers for mitochondrial biogenesis, one of the most important adaptive responses in skeletal muscle. Both cis-9,trans-11 (c9,t11) and trans-10,cis-12 (t10,c12) CLA isomers increased the expression of peroxisome proliferator-activated receptor ? coactivator 1? (PGC-1?), however, only the t10,c12 isomer, but not c9,t11, increased phosphorylation of AMP-activated protein kinase (AMPK) compared to the control. Among downstream biomarkers of PGC-1?, the CLA mixed isomer enhanced the expression of peroxisome proliferator-activated receptor-? (PPAR?). Both c9,t11 and t10,c12 CLA isomers increased expression of nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (Tfam), while the c9,t11 increased expression of cytochrome c (Cyt C) and t10,c12 CLA increased expression of voltage-dependent anion channel (VDAC), respectively. Both CLA isomers significantly increased mitochondrial DNA copy number compared to that of control. These findings suggest that the individual CLA isomers potentiate mitochondrial biogenesis via PGC-1?-NRF-1-Tfam signaling cascade, although downstream regulation may be isomer dependent. PMID:25720738

Kim, Yoo; Park, Yeonhwa

2015-04-01

114

Exercise-induced Bronchospasm In Children  

Microsoft Academic Search

This review will encompass definition, history, epidemiology, pathogenesis, diagnosis, and management of exerciseinduced\\u000a bronchospasm in the pediatric individual with and without known asthma. Exercise induced asthma is the conventional term for\\u000a transient airway narrowing in a known asthma in association with strenuous exercise usually lasting 5-10 minutes with a decline\\u000a in pulmonary function by at least 10%. Exercise induced

Chris Randolph

2008-01-01

115

Indoxyl Sulfate-Induced Oxidative Stress, Mitochondrial Dysfunction, and Impaired Biogenesis Are Partly Protected by Vitamin C and N-Acetylcysteine  

PubMed Central

Indoxyl sulfate (IS) contributes to oxidative stress and endothelial dysfunction in chronic kidney disease patients. However, the role of mitochondria in IS-induced oxidative stress is not very clear. In this study, we examined whether mitochondria play a pivotal role in modulating the effects of antioxidants during IS treatment. In the context of human umbilical vein endothelial cells, we found that IS had a dose-dependent antiproliferative effect. In addition, we used flow cytometry to demonstrate that the level of reactive oxygen species increased in a dose-dependent manner after treatment with IS. High doses of IS also corresponded to increased mitochondrial depolarization and decreased mitochondrial DNA copy number and mitochondrial mass. However, these effects could be reversed by the addition of antioxidants, namely, vitamin C and N-acetylcysteine. Thus, our results suggest that IS-induced oxidative stress and antiproliferative effect can be attributed to mitochondrial dysfunction and impaired biogenesis and that these processes can be protected by treatment with antioxidants.

Lee, Wen-Chin; Li, Lung-Chih; Chen, Jin-Bor; Chang, Hsueh-Wei

2015-01-01

116

PPR2263, a DYW-Subgroup Pentatricopeptide Repeat Protein, Is Required for Mitochondrial nad5 and cob Transcript Editing, Mitochondrion Biogenesis, and Maize Growth[C][W  

PubMed Central

RNA editing plays an important role in organelle gene expression in various organisms, including flowering plants, changing the nucleotide information at precise sites. Here, we present evidence that the maize (Zea mays) nuclear gene Pentatricopeptide repeat 2263 (PPR2263) encoding a DYW domain–containing PPR protein is required for RNA editing in the mitochondrial NADH dehydrogenase5 (nad5) and cytochrome b (cob) transcripts at the nad5-1550 and cob-908 sites, respectively. Its putative ortholog, MITOCHONDRIAL EDITING FACTOR29, fulfills the same role in Arabidopsis thaliana. Both the maize and the Arabidopsis proteins show preferential localization to mitochondria but are also detected in chloroplasts. In maize, the corresponding ppr2263 mutation causes growth defects in kernels and seedlings. Embryo and endosperm growth are reduced, leading to the production of small but viable kernels. Mutant plants have narrower and shorter leaves, exhibit a strong delay in flowering time, and generally do not reach sexual maturity. Whereas mutant chloroplasts do not have major defects, mutant mitochondria lack complex III and are characterized by a compromised ultrastructure, increased transcript levels, and the induction of alternative oxidase. The results suggest that mitochondrial RNA editing at the cob-908 site is necessary for mitochondrion biogenesis, cell division, and plant growth in maize. PMID:22319053

Sosso, Davide; Mbelo, Sylvie; Vernoud, Vanessa; Gendrot, Ghislaine; Dedieu, Annick; Chambrier, Pierre; Dauzat, Myriam; Heurtevin, Laure; Guyon, Virginie; Takenaka, Mizuki; Rogowsky, Peter M.

2012-01-01

117

The Single Nucleotide Polymorphism Gly482Ser in the PGC-1? Gene Impairs Exercise-Induced Slow-Twitch Muscle Fibre Transformation in Humans  

PubMed Central

PGC-1? (peroxisome proliferator-activated receptor ? co-activator 1?) is an important regulator of mitochondrial biogenesis and a master regulator of enzymes involved in oxidative phosphorylation. Recent evidence demonstrated that the Gly482Ser single nucleotide polymorphism (SNP) in the PGC-1? gene affects insulin sensitivity, blood lipid metabolism and binding to myocyte enhancer factor 2 (MEF2). Individuals carrying this SNP were shown to have a reduced cardiorespiratory fitness and a higher risk to develop type 2 diabetes. Here, we investigated the responses of untrained men with the Gly482Ser SNP to a 10 week programme of endurance training (cycling, 3 x 60 min/week, heart rate at 70-90% VO2peak). Quantitative data from analysis of biopsies from vastus lateralis muscle revealed that the SNP group, in contrast to the control group, lacked a training-induced increase in content of slow contracting oxidative fibres. Capillary supply, mitochondrial density, mitochondrial enzyme activities and intramyocellular lipid content increased similarly in both groups. These results indicate that the impaired binding of MEF2 to PGC-1? in humans with this SNP impedes exercise-induced fast-to-slow muscle fibre transformation. PMID:25886402

Steinbacher, Peter; Feichtinger, René G.; Kedenko, Lyudmyla; Kedenko, Igor; Reinhardt, Sandra; Schönauer, Anna-Lena; Leitner, Isabella; Sänger, Alexandra M.; Stoiber, Walter; Kofler, Barbara; Förster, Holger; Paulweber, Bernhard; Ring-Dimitriou, Susanne

2015-01-01

118

Cholinergic urticaria and exercise-induced anaphylaxis.  

PubMed

In this article, we will present the physical manifestations of two similar conditions. The first is cholinergic urticaria. This is chronic urticaria precipitated by an elevated body temperature. The second is exercise-induced anaphylaxis. Anaphylaxis can be idiopathic, a result of a specific allergenic trigger (food, medication, or insect sting), or exercise induced. We will focus on the third subtype. We describe the causes, symptoms, pathophysiology, testing, treatment, and prognosis of these two conditions. PMID:25574887

Montgomery, Stefan L

2015-01-01

119

Dynamic changes in mitochondrial biogenesis and antioxidant enzymes during the spontaneous differentiation of human embryonic stem cells  

Microsoft Academic Search

Embryonic cells before implantation are exposed to a hypoxic condition and dependent on anaerobic metabolism. Human embryonic stem cells (HESCs) derived from pre-implantation blastocyst also grow well in hypoxic conditions. Expecting that the differentiating HESCs might mimic anaerobic-to-aerobic metabolic transition of the early human life, we examined the mitochondria-related changes in these cells. We observed that mitochondrial mass and mitochondrial

Young Min Cho; Sujin Kwon; Youngmi Kim Pak; Hye Won Seol; Young Min Choi; Do Joon Park; Kyong Soo Park; Hong Kyu Lee

2006-01-01

120

Hypoglycemic effect of catalpol on high-fat diet/streptozotocin-induced diabetic mice by increasing skeletal muscle mitochondrial biogenesis.  

PubMed

Catalpol, an iridoid glycoside, exists in the root of Radix Rehmanniae. Some studies have shown that catalpol has a remarkable hypoglycemic effect in the streptozotocin-induced diabetic model, but the underlying mechanism for this effect has not been fully elucidated. Because mitochondrial dysfunction plays a vital role in the pathology of diabetes and because improving mitochondrial function may offer a new approach for the treatment of diabetes, this study was designed. Catalpol was orally administered together with metformin to high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice daily for 4 weeks. Body weight (BW), fasting blood glucose (FBG) level, and glucose disposal (IPGTT) were measured during or after the treatment. The results showed a dose-dependent reduction of FBG level with no apparent changes in BW through four successive weeks of catalpol administration. Catalpol treatment substantially reduced serum total cholesterol and triglyceride levels in the diabetic mice. In addition, catalpol efficiently increased mitochondrial ATP production and reversed the decrease of mitochondrial membrane potential and mtDNA copy number in skeletal muscle tissue. Furthermore, catalpol (200 mg/kg) rescued mitochondrial ultrastructure in skeletal muscle, as detected with transmission electron microscopy. The relative mRNA level of peroxisome proliferator-activated receptor gamma co-activator 1 (PGC1) ? was significantly decreased in muscle tissue of diabetic mice, while this effect was reversed by catalpol, resulting in a dose-dependent up-regulation. Taken together, we found that catalpol was capable of lowering FBG level via improving mitochondrial function in skeletal muscle of HFD/STZ-induced diabetic mice. PMID:25178463

Li, Xia; Xu, Zhimeng; Jiang, Zhenzhou; Sun, Lixin; Ji, Jinzi; Miao, Jingshan; Zhang, Xueji; Li, Xiaojie; Huang, Shan; Wang, Tao; Zhang, Luyong

2014-09-01

121

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit  

PubMed Central

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle. PMID:22447445

He, J.; Cooper, H. M.; Reyes, A.; Di Re, M.; Kazak, L.; Wood, S. R.; Mao, C. C.; Fearnley, I. M.; Walker, J. E.; Holt, I. J.

2012-01-01

122

Human C4orf14 interacts with the mitochondrial nucleoid and is involved in the biogenesis of the small mitochondrial ribosomal subunit.  

PubMed

The bacterial homologue of C4orf14, YqeH, has been linked to assembly of the small ribosomal subunit. Here, recombinant C4orf14 isolated from human cells, co-purified with the small, 28S subunit of the mitochondrial ribosome and the endogenous protein co-fractionated with the 28S subunit in sucrose gradients. Gene silencing of C4orf14 specifically affected components of the small subunit, leading to decreased protein synthesis in the organelle. The GTPase of C4orf14 was critical to its interaction with the 28S subunit, as was GTP. Therefore, we propose that C4orf14, with bound GTP, binds to components of the 28S subunit facilitating its assembly, and GTP hydrolysis acts as the release mechanism. C4orf14 was also found to be associated with human mitochondrial nucleoids, and C4orf14 gene silencing caused mitochondrial DNA depletion. In vitro C4orf14 is capable of binding to DNA. The association of C4orf14 with mitochondrial translation factors and the mitochondrial nucleoid suggests that the 28S subunit is assembled at the mitochondrial nucleoid, enabling the direct transfer of messenger RNA from the nucleoid to the ribosome in the organelle. PMID:22447445

He, J; Cooper, H M; Reyes, A; Di Re, M; Kazak, L; Wood, S R; Mao, C C; Fearnley, I M; Walker, J E; Holt, I J

2012-07-01

123

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats  

Microsoft Academic Search

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance

Hyun Woo Jeong; Si Young Cho; Shinae Kim; Eui Seok Shin; Jae Man Kim; Min Jeong Song; Pil Joon Park; Jong Hee Sohn; Hyon Park; Dae-Bang Seo; Wan Gi Kim; Sang-Jun Lee

2012-01-01

124

Co-regulation of nuclear respiratory factor-1 by NF?B and CREB links LPS-induced inflammation to mitochondrial biogenesis  

PubMed Central

The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NF?B, and identified interspecies-conserved ?B-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NF?B, and in LPS-treated hepatocytes, NF?B served as an NRF1 enhancer element in conjunction with NF?B promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting ?B-element mutations, and nuclear accumulation of NF?B and CREB demonstrated dependence on mitochondrial H2O2. These findings indicate that TLR4-dependent NF?B and CREB activation co-regulate the NRF1 promoter with NF?B intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses. PMID:20587593

Suliman, Hagir B.; Sweeney, Timothy E.; Withers, Crystal M.; Piantadosi, Claude A.

2010-01-01

125

Roles for the lipid-signaling enzyme MitoPLD in mitochondrial dynamics, piRNA biogenesis, and spermatogenesis  

PubMed Central

Phospholipase D (PLD), a superfamily of signaling enzymes that most commonly generate the lipid second messenger Phosphatidic Acid (PA), is found in diverse organisms from bacteria to man and functions in multiple cellular pathways. A fascinating member of the family, MitoPLD, is anchored to the mitochondrial surface and has two reported roles. In the first role, MitoPLD-generated PA regulates mitochondrial shape through facilitating mitochondrial fusion. In the second role, MitoPLD performs a critical function in a pathway that creates a specialized form of RNAi required by developing spermatocytes to suppress transposon mobilization during meiosis. This spermatocyte-specific RNAi, known as piRNA, is generated in the nuage, an electron-dense accumulation of RNA templates and processing proteins that localize adjacent to mitochondria in a structure also called intermitochondrial cement. In this review, we summarize recent findings on these roles for MitoPLD functions, highlighting directions that need to be pursued to define the underlying mechanisms. PMID:22281006

Gao, Qun; Frohman, Michael A.

2013-01-01

126

Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus.  

PubMed

We measured plasma levels of the oxidative DNA damage marker 8-hydroxy-2'-deoxyguanosine (8-OHdG) and leucocyte mRNA expression levels of the genes encoding the 8-OHdG repair enzyme human 8-oxoguanine DNA glycosylase 1 (hOGG1), the anti-oxidant enzymes copper/zinc superoxide dismutase (Cu/ZnSOD), manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase-1 (GPx-1), GPx-4, glutathione reductase (GR) and glutathione synthetase (GS), the mitochondrial biogenesis-related proteins mtDNA-encoded ND 1 polypeptide (ND1), ND6, ATPase 6, mitochondrial transcription factor A (Tfam), nuclear respiratory factor 1(NRF-1), pyruvate dehydrogenase E1 component alpha subunit (PDHA1), pyruvate dehydrogenase kinase isoenzyme 1 (PDK-1) and hypoxia inducible factor-1? (HIF-1?) and the glycolytic enzymes hexokinase-II (HK-II), glucose 6-phosphate isomerase (GPI), phosphofructokinase (PFK), glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and lactate dehydrogenase A (LDHa). We analysed their relevance to oxidative damage in 85 systemic lupus erythematosus (SLE) patients, four complicated SLE patients undergoing rituximab treatment and 45 healthy individuals. SLE patients had higher plasma 8-OHdG levels (P?mitochondrial biogenesis-related proteins (P?mitochondrial biogenesis-related proteins (P?mitochondrial biogenesis and glucose metabolism may be implicated in SLE deterioration, and this impairment might be improved by targeted biological therapy. PMID:24345202

Lee, H-T; Lin, C-S; Lee, C-S; Tsai, C-Y; Wei, Y-H

2014-04-01

127

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1?  

PubMed Central

Previous investigations show that intracerebroventricular administration of a potent inhibitor of fatty acid synthase, C75, increases the level of its substrate, malonyl-CoA, in the hypothalamus. The “malonyl-CoA signal” is rapidly transmitted to skeletal muscle by the sympathetic nervous system, increasing fatty acid oxidation, uncoupling protein-3 (UCP3) expression, and thus, energy expenditure. Here, we show that intracerebroventricular or intraperitoneal administration of C75 increases the number of mitochondria in white and red (soleus) skeletal muscle. Consistent with signal transmission from the hypothalamus by the sympathetic nervous system, centrally administered C75 rapidly (?2 h) up-regulated the expression (in skeletal muscle) of the ?-adrenergic signaling molecules, i.e., norepinephrine, ?3-adrenergic receptor, and cAMP; the transcriptional regulators peroxisomal proliferator activator regulator ? coactivator 1? (PGC-1?) and estrogen receptor-related receptor ? (ERR?); and the expression of key oxidative mitochondrial enzymes, including pyruvate dehydrogenase kinase, medium-chain length fatty acyl-CoA dehydrogenase, ubiquinone–cytochrome c reductase, cytochrome oxidase, as well as ATP synthase and UCP3. The role of PGC-1? in mediating these responses in muscle was assessed with C2C12 myocytes in cell culture. Consistent with the in vivo response, adenovirus-directed expression of PGC-1? in C2C12 muscle cells provoked the phosphorylation/inactivation and reduced expression of acetyl-CoA carboxylase 2, causing a reduction of the malonyl-CoA concentration. These effects, coupled with an increased carnitine palmitoyltransferase 1b, led to increased fatty acid oxidation. PGC-1? also increased the expression of ERR?, PPAR?, and enzymes that support mitochondrial fatty acid oxidation, ATP synthesis, and thermogenesis, apparently mediated by an increased expression of UCP3. PMID:17030788

Cha, Seung-Hun; Rodgers, Joseph T.; Puigserver, Pere; Chohnan, Shigeru; Lane, M. Daniel

2006-01-01

128

Hypothalamic malonyl-CoA triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle: Role of PGC-1alpha.  

PubMed

Previous investigations show that intracerebroventricular administration of a potent inhibitor of fatty acid synthase, C75, increases the level of its substrate, malonyl-CoA, in the hypothalamus. The "malonyl-CoA signal" is rapidly transmitted to skeletal muscle by the sympathetic nervous system, increasing fatty acid oxidation, uncoupling protein-3 (UCP3) expression, and thus, energy expenditure. Here, we show that intracerebroventricular or intraperitoneal administration of C75 increases the number of mitochondria in white and red (soleus) skeletal muscle. Consistent with signal transmission from the hypothalamus by the sympathetic nervous system, centrally administered C75 rapidly (< or =2 h) up-regulated the expression (in skeletal muscle) of the beta-adrenergic signaling molecules, i.e., norepinephrine, beta3-adrenergic receptor, and cAMP; the transcriptional regulators peroxisomal proliferator activator regulator gamma coactivator 1alpha (PGC-1alpha) and estrogen receptor-related receptor alpha (ERRalpha); and the expression of key oxidative mitochondrial enzymes, including pyruvate dehydrogenase kinase, medium-chain length fatty acyl-CoA dehydrogenase, ubiquinone-cytochrome c reductase, cytochrome oxidase, as well as ATP synthase and UCP3. The role of PGC-1alpha in mediating these responses in muscle was assessed with C2C12 myocytes in cell culture. Consistent with the in vivo response, adenovirus-directed expression of PGC-1alpha in C2C12 muscle cells provoked the phosphorylation/inactivation and reduced expression of acetyl-CoA carboxylase 2, causing a reduction of the malonyl-CoA concentration. These effects, coupled with an increased carnitine palmitoyltransferase 1b, led to increased fatty acid oxidation. PGC-1alpha also increased the expression of ERRalpha, PPARalpha, and enzymes that support mitochondrial fatty acid oxidation, ATP synthesis, and thermogenesis, apparently mediated by an increased expression of UCP3. PMID:17030788

Cha, Seung-Hun; Rodgers, Joseph T; Puigserver, Pere; Chohnan, Shigeru; Lane, M Daniel

2006-10-17

129

Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes.  

PubMed

The aim was to determine if the metabolic adaptations, particularly PGC-1? and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg(-1)·min(-1), n = 15) completed 4 h cycling at ~56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg(-1)·dw(-1)) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-? gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1?, TFAM, NRF-1, COX-IV, PPAR-?, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained. PMID:25677542

Jensen, Line; Gejl, Kasper D; Ørtenblad, Niels; Nielsen, Jakob L; Bech, Rune D; Nygaard, Tobias; Sahlin, Kent; Frandsen, Ulrik

2015-02-01

130

Carbohydrate restricted recovery from long term endurance exercise does not affect gene responses involved in mitochondrial biogenesis in highly trained athletes  

PubMed Central

The aim was to determine if the metabolic adaptations, particularly PGC-1? and downstream metabolic genes were affected by restricting CHO following an endurance exercise bout in trained endurance athletes. A second aim was to compare baseline expression level of these genes to untrained. Elite endurance athletes (VO2max 66 ± 2 mL·kg?1·min?1, n = 15) completed 4 h cycling at ?56% VO2max. During the first 4 h recovery subjects were provided with either CHO or only H2O and thereafter both groups received CHO. Muscle biopsies were collected before, after, and 4 and 24 h after exercise. Also, resting biopsies were collected from untrained subjects (n = 8). Exercise decreased glycogen by 67.7 ± 4.0% (from 699 ± 26.1 to 239 ± 29.5 mmol·kg?1·dw?1) with no difference between groups. Whereas 4 h of recovery with CHO partly replenished glycogen, the H2O group remained at post exercise level; nevertheless, the gene expression was not different between groups. Glycogen and most gene expression levels returned to baseline by 24 h in both CHO and H2O. Baseline mRNA expression of NRF-1, COX-IV, GLUT4 and PPAR-? gene targets were higher in trained compared to untrained. Additionally, the proportion of type I muscle fibers positively correlated with baseline mRNA for PGC-1?, TFAM, NRF-1, COX-IV, PPAR-?, and GLUT4 for both trained and untrained. CHO restriction during recovery from glycogen depleting exercise does not improve the mRNA response of markers of mitochondrial biogenesis. Further, baseline gene expression of key metabolic pathways is higher in trained than untrained. PMID:25677542

Jensen, Line; Gejl, Kasper D; Ørtenblad, Niels; Nielsen, Jakob L; Bech, Rune D; Nygaard, Tobias; Sahlin, Kent; Frandsen, Ulrik

2015-01-01

131

Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1? genes  

PubMed Central

Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter’s redox reactions to yield hydrogen peroxide (H2O2), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1? (PGC-1?), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H2O2, a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O2-. and H2O2. As Sirt1 and PGC-1? profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases. PMID:23228932

Kamble, Pratibha; Selvarajan, Krithika; Narasimhulu, Chandrakala Aluganti; Nandave, Mukesh; Parthasarathy, Sampath

2013-01-01

132

Aspirin may promote mitochondrial biogenesis via the production of hydrogen peroxide and the induction of Sirtuin1/PGC-1? genes.  

PubMed

Based on the rapid hydrolysis of acetyl salicylic acid (ASA, Aspirin) to salicylic acid (SA), the ability of SA to form dihydroxy benzoic acid (DBA), and the latter's redox reactions to yield hydrogen peroxide (H(2)O(2)), we predicted that ASA may have the potential to induce Sirtuin1 (Sirt1) and its downstream effects. We observed that treatment of cultured liver cells with ASA resulted in the induction of Sirt1, peroxisome proliferator-activated receptor-gamma co-activator-1? (PGC-1?), and NAD(P)H quinone oxidoreductase 1 (Nqo1) genes. Paraoxonase 1 (PON1) and Aryl hydrocarbon receptor (AhR) siRNA transfections inhibited the induction of gene expressions by ASA suggesting the need for the acetyl ester hydrolysis and hydroxylation to DHBA. The latter also induced Sirt1, confirming the proposed pathway. As predicted, ASA and SA treatment resulted in the production of H(2)O(2), a known inducer of Sirt1 and confirmed in the current studies. More importantly, ASA treatment resulted in an increase in mitochondria as seen by tracking dyes. We suggest that DHBA, generated from ASA, via its oxidation/reduction reactions mediated by Nqo1 might be involved in the production of O(2)(-.) and H(2)O(2). As Sirt1 and PGC-1? profoundly affect mitochondrial metabolism and energy utilization, ASA may have therapeutic potential beyond its ability to inhibit cyclooxygenases. PMID:23228932

Kamble, Pratibha; Selvarajan, Krithika; Aluganti Narasimhulu, Chandrakala; Nandave, Mukesh; Parthasarathy, Sampath

2013-01-15

133

Genes involved in mitochondrial biogenesis\\/function are induced in response to bilio-pancreatic diversion in morbidly obese individuals with normal glucose tolerance but not in type 2 diabetic patients  

Microsoft Academic Search

Aims\\/hypothesis  The mechanisms allowing normalisation of insulin sensitivity and reversal of type 2 diabetes after bilio-pancreatic diversion\\u000a (BPD) have not been elucidated. We studied whether the expression of genes relevant to mitochondrial biogenesis\\/function is\\u000a induced in response to BPD and whether the response differs between morbidly obese patients with normal glucose tolerance\\u000a (NGT) and patients with type 2 diabetes.\\u000a \\u000a \\u000a \\u000a Methods  The effect

M. I. Hernández-Alvarez; C. Chiellini; M. Manco; D. Naon; M. Liesa; M. Palacín; G. Mingrone; A. Zorzano

2009-01-01

134

Mechanisms of Exercise-Induced Cardioprotection  

PubMed Central

Myocardial ischemia-reperfusion (IR) injury can cause ventricular cell death and is a major pathological event leading to morbidity and mortality in those with coronary artery disease. Interestingly, as few as five bouts of exercise on consecutive days can rapidly produce a cardiac phenotype that resists IR-induced myocardial injury. This review summarizes the development of exercise-induced cardioprotection and the mechanisms responsible for this important adaptive response. PMID:24382869

Smuder, Ashley J.; Kavazis, Andreas N.; Quindry, John C.

2014-01-01

135

Acrosome biogenesis  

PubMed Central

The acrosome is a unique membranous organelle located over the anterior part of the sperm nucleus that is highly conserved throughout evolution. This acidic vacuole contains a number of hydrolytic enzymes that, when secreted, help the sperm penetrate the egg's coats. Although acrosome biogenesis is an important aspect of spermiogenesis, the molecular mechanism(s) that regulates this event remains unknown. Active trafficking from the Golgi apparatus is involved in acrosome formation, but experimental evidence indicates that trafficking of vesicles out of the Golgi also occurs during acrosomogenesis. Unfortunately, this second aspect of acrosome biogenesis remains poorly studied. In this article, we briefly discuss how the biosynthetic and endocytic pathways, assisted by a network of microtubules, tethering factors, motor proteins and small GTPases, relate and connect to give rise to the sperm-specific vacuole, with a particular emphasis placed on the endosomal compartment. It is hoped that this information will be useful to engage more studies on acrosome biogenesis by focusing attention towards suggested directions. PMID:22319656

Paiardi, Chiara

2011-01-01

136

Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats.  

PubMed

Controversy exists as to whether supplementation with the antioxidants vitamin E and vitamin C blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial function and induces insulin resistance (IR), no data exist as to whether supplementation with vitamin E and vitamin C modify responses to exercise in pre-existing obesity. We tested the hypothesis that dietary supplementation with vitamin E (0.4 g ?-tocopherol acetate/kg) and vitamin C (0.5 g/kg) blocks exercise-induced improvements on IR and mitochondrial content in obese rats maintained on a high-fat (45% fat energy (en)) diet. Diet-induced obese, sedentary rats had a 2-fold higher homeostasis model assessment of insulin resistance and larger insulin area under the curve following glucose tolerances test than rats fed a low-fat (10% fat en) diet. Exercising (12 weeks at 5 times per week in a motorized wheel) of obese rats normalized IR indices, an effect not modified by vitamin E and vitamin C. Vitamin E and vitamin C supplementation with exercise elevated mtDNA content in adipose and skeletal muscle to a greater extent (20%) than exercise alone in a depot-specific manner. On the other hand, vitamin C and vitamin E decreased exercise-induced increases in mitochondrial protein content for complex I (40%) and nicotinamide nucleotide transhydrogenase (35%) in a muscle-dependent manner. These data indicate that vitamin E and vitamin C supplementation in obese rodents does not modify exercise-induced improvements in insulin sensitivity but that changes in mitochondrial biogenesis and mitochondrial protein expression may be modified by antioxidant supplementation. PMID:25761734

Picklo, Matthew J; Thyfault, John P

2015-04-01

137

Food-dependent exercise-induced anaphylaxis.  

PubMed

A 58-year-old farmer was admitted to our hospital because of repeated episodes of anaphylaxis. He had experienced 12 episodes of anaphylactic shock over the previous 17 years. These attacks included three episodes of bee sting. In general, the episodes occurred during farm work (exercise) and within two hours of eating cake in the afternoon. Because an immediate skin reaction to wheat flour was highly positive, a diagnosis of wheat allergy was considered. These findings suggested that his illness was consistent with food-dependent exercise-induced anaphylaxis. PMID:1477465

Okazaki, M; Kitani, H; Mifune, T; Mitsunobu, F; Saito, S; Asaumi, N; Tanizaki, Y

1992-08-01

138

Imitators of exercise-induced bronchoconstriction  

PubMed Central

Exercise-induced bronchoconstriction (EIB) is described by transient narrowing of the airways after exercise. It occurs in approximately 10% of the general population, while athletes may show a higher prevalence, especially in cold weather and ice rink athletes. Diagnosis of EIB is often made on the basis of self-reported symptoms without objective lung function tests, however, the presence of EIB can not be accurately determined on the basis of symptoms and may be under-, over-, or misdiagnosed. The goal of this review is to describe other clinical entities that mimic asthma or EIB symptoms and can be confused with EIB. PMID:20016690

2009-01-01

139

The functional interaction of mitochondrial Hsp70s with the escort protein Zim17 is critical for Fe/S biogenesis and substrate interaction at the inner membrane preprotein translocase.  

PubMed

The yeast protein Zim17 belongs to a unique class of co-chaperones that maintain the solubility of Hsp70 proteins in mitochondria and plastids of eukaryotic cells. However, little is known about the functional cooperation between Zim17 and mitochondrial Hsp70 proteins in vivo. To analyze the effects of a loss of Zim17 function in the authentic environment, we introduced novel conditional mutations within the ZIM17 gene of the model organism Saccharomyces cerevisiae that allowed a recovery of temperature-sensitive but respiratory competent zim17 mutant cells. On fermentable growth medium, the mutant cells were prone to acquire respiratory deficits and showed a strong aggregation of the mitochondrial Hsp70 Ssq1 together with a concomitant defect in Fe/S protein biogenesis. In contrast, under respiring conditions, the mitochondrial Hsp70s Ssc1 and Ssq1 exhibited only a partial aggregation. We show that the induction of the zim17 mutant phenotype leads to strong import defects for Ssc1-dependent matrix-targeted precursor proteins that correlate with a significantly reduced binding of newly imported substrate proteins to Ssc1. We conclude that Zim17 is not only required for the maintenance of mtHsp70 solubility but also directly assists the functional interaction of mtHsp70 with substrate proteins in a J-type co-chaperone-dependent manner. PMID:24030826

Lewrenz, Ilka; Rietzschel, Nicole; Guiard, Bernard; Lill, Roland; van der Laan, Martin; Voos, Wolfgang

2013-10-25

140

Suppression of mitochondrial biogenesis through toll-like receptor 4-dependent mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling in endotoxin-induced acute kidney injury.  

PubMed

Although disruption of mitochondrial homeostasis and biogenesis (MB) is a widely accepted pathophysiologic feature of sepsis-induced acute kidney injury (AKI), the molecular mechanisms responsible for this phenomenon are unknown. In this study, we examined the signaling pathways responsible for the suppression of MB in a mouse model of lipopolysaccharide (LPS)-induced AKI. Downregulation of peroxisome proliferator-activated receptor ? coactivator-1? (PGC-1?), a master regulator of MB, was noted at the mRNA level at 3 hours and protein level at 18 hours in the renal cortex, and was associated with loss of renal function after LPS treatment. LPS-mediated suppression of PGC-1? led to reduced expression of downstream regulators of MB and electron transport chain proteins along with a reduction in renal cortical mitochondrial DNA content. Mechanistically, Toll-like receptor 4 (TLR4) knockout mice were protected from renal injury and disruption of MB after LPS exposure. Immunoblot analysis revealed activation of tumor progression locus 2/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (TPL-2/MEK/ERK) signaling in the renal cortex by LPS. Pharmacologic inhibition of MEK/ERK signaling attenuated renal dysfunction and loss of PGC-1?, and was associated with a reduction in proinflammatory cytokine (e.g., tumor necrosis factor-? [TNF-?], interleukin-1?) expression at 3 hours after LPS exposure. Neutralization of TNF-? also blocked PGC-1? suppression, but not renal dysfunction, after LPS-induced AKI. Finally, systemic administration of recombinant tumor necrosis factor-? alone was sufficient to produce AKI and disrupt mitochondrial homeostasis. These findings indicate an important role for the TLR4/MEK/ERK pathway in both LPS-induced renal dysfunction and suppression of MB. TLR4/MEK/ERK/TNF-? signaling may represent a novel therapeutic target to prevent mitochondrial dysfunction and AKI produced by sepsis. PMID:25503387

Smith, Joshua A; Stallons, L Jay; Collier, Justin B; Chavin, Kenneth D; Schnellmann, Rick G

2015-02-01

141

Identifying exercise allergies: exercise-induced anaphylaxis and cholinergic urticaria.  

PubMed

Exercise-related allergies vary from the benign rash of cholinergic urticaria to life-threatening exercise-induced anaphylaxis. Rapid diagnosis is essential, but it can be difficult to tell the two conditions apart. The size of the wheals and the patient history provide the best clues. Giving epinephrine and taking steps to protect the patient's airway, breathing, and circulation are standard treatment for exercise-induced anaphylaxis. Effective management for less severe cases involves exercising with a partner, keeping self-injectable epinephrine on hand, and avoiding exercise before and after meals. Prophylactic antihistamines are more effective for cholinergic urticaria than for exercise-induced anaphylaxis. PMID:20086959

Terrell, T; Hough, D O; Alexander, R

1996-11-01

142

DEMONSTRATION BULLETIN: BIOGENESIS SOIL WASHING TECHNOLOGY - BIOGENESIS  

EPA Science Inventory

The BioGenesisSM soil washing technology was developed by BioGenesis Enterprises, Inc. to remove organic compounds from soil. The technology uses a proprietary solution (BioGenesisSM cleaner) to transfer organic compounds from the soil matrix to a liquid phase. BioGenesis claims...

143

Exercise-induced asthma and cardiovascular fitness in asthmatic children  

Microsoft Academic Search

BACKGROUND: The role of physical training in the management of children with exercise-induced asthma is controversial. A study was undertaken to determine whether a relationship could be found between the occurrence of exercise-induced asthma and the degree of cardiovascular fitness in asthmatic children. METHODS: Twenty eight children aged 6-13 with mild to moderate asthma and dyspnoea during or after physical

B. J. Thio; A. F. Nagelkerke; A. G. Ketel; B. L. van Keeken; J. E. Dankert-Roelse

1996-01-01

144

Defects of mtDNA Replication Impaired Mitochondrial Biogenesis During Trypanosoma cruzi Infection in Human Cardiomyocytes and Chagasic Patients: The Role of Nrf1/2 and Antioxidant Response  

PubMed Central

Background Mitochondrial dysfunction is a key determinant in chagasic cardiomyopathy development in mice; however, its relevance in human Chagas disease is not known. We determined if defects in mitochondrial biogenesis and dysregulation of peroxisome proliferator-activated receptor gamma (PPAR?) coactivator-1 (PGC-1)–regulated transcriptional pathways constitute a mechanism or mechanisms underlying mitochondrial oxidative-phosphorylation (OXPHOS) deficiency in human Chagas disease. Methods and Results We utilized human cardiomyocytes and left-ventricular tissue from chagasic and other cardiomyopathy patients and healthy donors (n>6/group). We noted no change in citrate synthase activity, yet mRNA and/or protein levels of subunits of the respiratory complexes were significantly decreased in Trypanosoma cruzi–infected cardiomyocytes (0 to 24 hours) and chagasic hearts. We observed increased mRNA and decreased nuclear localization of PGC-1-coactivated transcription factors, yet the expression of genes for PPAR?-regulated fatty acid oxidation and nuclear respiratory factor (NRF1/2)–regulated mtDNA replication and transcription machinery was enhanced in infected cardiomyocytes and chagasic hearts. The D-loop formation was normal or higher, but mtDNA replication and mtDNA content were decreased by 83% and 40% to 65%, respectively. Subsequently, we noted that reactive oxygen species (ROS), oxidative stress, and mtDNA oxidation were significantly increased, yet NRF1/2-regulated antioxidant gene expression remained compromised in infected cardiomyocytes and chagasic hearts. Conclusions The replication of mtDNA was severely compromised, resulting in a significant loss of mtDNA and expression of OXPHOS genes in T cruzi–infected cardiomyocytes and chagasic hearts. Our data suggest increased ROS generation and selective functional incapacity of NRF2-mediated antioxidant gene expression played a role in the defects in mtDNA replication and unfitness of mtDNA for replication and gene expression in Chagas disease. PMID:23316324

Wan, Xianxiu; Gupta, Shivali; Zago, Maria P.; Davidson, Mercy M.; Dousset, Pierre; Amoroso, Alejandro; Garg, Nisha Jain

2012-01-01

145

Exercise- and training-induced upregulation of skeletal muscle fatty acid oxidation are not solely dependent on mitochondrial machinery and biogenesis.  

PubMed

? Regulation of skeletal muscle fatty acid oxidation (FAO) and adaptation to exercise training have long been thought to depend on delivery of fatty acids (FAs) to muscle, their diffusion into muscle, and muscle mitochondrial content and biochemical machinery. However, FA entry into muscle occurs via a regulatable, protein-mediated mechanism, involving several transport proteins. Among these CD36 is key. Muscle contraction and pharmacological agents induce CD36 to translocate to the cell surface, a response that regulates FA transport, and hence FAO. In exercising CD36 KO mice, exercise duration (-44%), and FA transport (-41%) and oxidation (-37%) are comparably impaired, while carbohydrate metabolism is augmented. In trained CD36 KO mice, training-induced upregulation of FAO is not observed, despite normal training-induced increases in mitochondrial density and enzymes. Transfecting CD36 into sedentary WT muscle (+41%), comparable to training-induced CD36 increases (+44%) in WT muscle, markedly upregulates FAO to rates observed in trained WT mice, but without any changes in mitochondrial density and enzymes. Evidently, in vivo CD36-mediated FA transport is key for muscle fuel selection and training-induced FAO upregulation, independent of mitochondrial adaptations. This CD36 molecular mechanism challenges the view that skeletal muscle FAO is solely regulated by muscle mitochondrial content and machinery. PMID:22890711

Yoshida, Yuko; Jain, Swati S; McFarlan, Jay T; Snook, Laelie A; Chabowski, Adrian; Bonen, Arend

2013-09-15

146

Targeting of NH2-terminal–processed Microsomal Protein to Mitochondria: A Novel Pathway for the Biogenesis of Hepatic Mitochondrial P450MT2  

PubMed Central

Cytochrome P4501A1 is a hepatic, microsomal membrane–bound enzyme that is highly induced by various xenobiotic agents. Two NH2-terminal truncated forms of this P450, termed P450MT2a and MT2b, are also found localized in mitochondria from ?-naphthoflavone–induced livers. In this paper, we demonstrate that P4501A1 has a chimeric NH2-terminal signal that facilitates the targeting of the protein to both the ER and mitochondria. The NH2-terminal 30–amino acid stretch of P4501A1 is thought to provide signals for ER membrane insertion and also stop transfer. The present study provides evidence that a sequence motif immediately COOH-terminal (residues 33–44) to the transmembrane domain functions as a mitochondrial targeting signal under both in vivo and in vitro conditions, and that the positively charged residues at positions 34 and 39 are critical for mitochondrial targeting. Results suggest that 25% of P4501A1 nascent chains, which escape ER membrane insertion, are processed by a liver cytosolic endoprotease. We postulate that the NH2-terminal proteolytic cleavage activates a cryptic mitochondrial targeting signal. Immunofluorescence microscopy showed that a portion of transiently expressed P4501A1 is colocalized with the mitochondrial-specific marker protein cytochrome oxidase subunit I. The mitochondrial-associated MT2a and MT2b are localized within the inner membrane compartment, as tested by resistance to limited proteolysis in both intact mitochondria and mitoplasts. Our results therefore describe a novel mechanism whereby proteins with chimeric signal sequence are targeted to the ER as well as to the mitochondria. PMID:9348277

Addya, Sankar; Anandatheerthavarada, Hindupur K.; Biswas, Gopa; Bhagwat, Shripad V.; Mullick, Jayati; Avadhani, Narayan G.

1997-01-01

147

Exercise-induced bronchoconstriction in Tunisian elite athletes is underdiagnosed  

PubMed Central

Many studies have shown an increased risk of developing exercise-induced bronchoconstriction among the athletic population, particularly at the elite level. Subjective methods for assessing exercise-induced bronchoconstriction such as surveys and questionnaires have been used but have resulted in an underestimation of the prevalence of airway dysfunction when compared with objective measurements. The aim of the present study was to compare the prevalence of exercise-induced bronchoconstriction among Tunisian elite athletes obtained using an objective method with that using a subjective method, and to discuss the possible causes and implications of the observed discrepancy. As the objective method we used spirometry before and after exercise and for the subjective approach we used a medical history questionnaire. All of the recruited 107 elite athletes responded to the questionnaire about respiratory symptoms and medical history and underwent a resting spirometry testing before and after exercise. Post-exercise spirometry revealed the presence of exercise-induced bronchoconstriction in 14 (13%) of the elite athletes, while only 1.8% reported having previously been diagnosed with asthma. In conclusion, our findings indicate that medical history-based diagnoses of exercise-induced bronchoconstriction lead to underestimations of true sufferers. PMID:24198569

Sallaoui, Ridha; Zendah², Ines; Ghedira², Habib; Belhaouz³, Mohcine; Ghrairi³, Mourad; Amri³, Mohamed

2011-01-01

148

Indomethacin attenuates exercise-induced proteinuria in hypertensive miniature swine.  

PubMed

Exercise-induced proteinuria may be increased in hypertensives. The mechanisms underlying the increased proteinuria are not known, and it has not been determined whether animal models of hypertension exhibit a similar response. We investigated whether indomethacin (Indo) altered exercise-induced proteinuria in normal and hypertensive deoxycorticosterone acetate (DOCA) Yucatan miniature swine (YMS). Five normal and four DOCA YMS underwent 30 min of treadmill exercise at 80% of maximal heart rate. Cumulative (exercise + recovery) albumin excretion in the DOCA YMS was 25-fold (P < 0.01) greater than observed in the normal YMS. Indo had no effect on resting or exercise-induced proteinuria in the normal YMS. However, Indo decreased the slightly elevated proteinuria at rest, and normalized the exaggerated exercise-induced proteinuria in the DOCA YMS. The antiproteinuric effect of Indo in the DOCA YMS was not associated with altered exercise, recovery blood pressure, or glomerular filtration rate. Thus hypertensive DOCA YMS exhibit an exaggerated exercise-induced proteinuria. It is suggested that eicosanoids are involved in this abnormal renal proteinuric response to exercise. PMID:1415809

O'Hagan, K P; Hora, D F; Zambraski, E J

1992-10-01

149

Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues.  

PubMed

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion. PMID:25874021

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Pollio, Antonino; Venditti, Paola

2015-01-01

150

Dietary Supplementation with the Microalga Galdieria sulphuraria (Rhodophyta) Reduces Prolonged Exercise-Induced Oxidative Stress in Rat Tissues  

PubMed Central

We studied the effects of ten-day 1% Galdieria sulphuraria dietary supplementation on oxidative damage and metabolic changes elicited by acute exercise (6-hour swimming) determining oxygen consumption, lipid hydroperoxides, protein bound carbonyls in rat tissue (liver, heart, and muscle) homogenates and mitochondria, tissue glutathione peroxidase and glutathione reductase activities, glutathione content, and rates of H2O2 mitochondrial release. Exercise increased oxidative damage in tissues and mitochondria and decreased tissue content of reduced glutathione. Moreover, it increased State 4 and decreased State 3 respiration in tissues and mitochondria. G. sulphuraria supplementation reduced the above exercise-induced variations. Conversely, alga supplementation was not able to modify the exercise-induced increase in mitochondrial release rate of hydrogen peroxide and in liver and heart antioxidant enzyme activities. The alga capacity to reduce lipid oxidative damage without reducing mitochondrial H2O2 release can be due to its high content of C-phycocyanin and glutathione, which are able to scavenge peroxyl radicals and contribute to phospholipid hydroperoxide metabolism, respectively. In conclusion, G. sulphuraria ability to reduce exercise-linked oxidative damage and mitochondrial dysfunction makes it potentially useful even in other conditions leading to oxidative stress, including hyperthyroidism, chronic inflammation, and ischemia/reperfusion.

Carfagna, Simona; Napolitano, Gaetana; Barone, Daniela; Pinto, Gabriele; Venditti, Paola

2015-01-01

151

A Case of Wheat-Dependent Exercise-Induced Anaphylaxis  

PubMed Central

Foods are recognized as a common cause of urticaria; however, the role of food is considered to be more important in acute not chronic urticaria. Wheat is a basic ingredient found in many common foods. Food allergy to wheat is primarily described in children in the form of atopic dermatitis. It is rare in adults; where it is mainly reported in exercise-induced anaphylaxis. We report a case of wheat dependent exercise-induced anaphylaxis that occurred in a 54-year-old Korean woman. PMID:20523846

Lee, Hee Bong; Ahn, In Su; Choi, Ji Hoon; Park, Chun Wook

2009-01-01

152

Exercise-induced asthma. What family physicians should do.  

PubMed Central

Exercise-induced asthma is described as a transitory increase in airway resistance during or after vigorous exercise. Nearly 90% of patients with chronic asthma and 40% of allergic nonasthmatic patients have the condition. Family physicians should try to educate patients about their asthma and, barring contraindications, encourage them to participate in regular physical activity. PMID:8563507

D'Urzo, A.

1995-01-01

153

EXERCISE-INDUCED PULMONARY HEMORRHAGE AFTER RUNNING A MARATHON  

EPA Science Inventory

We report on a healthy 26-year-old male who had an exercise-induced pulmonary hemorrhage (EIPH) within 24 hours of running a marathon. There were no symptoms, abnormalities on exam, or radiographic infiltrates. He routinely participated in bronchoscopy research and the EIPH was e...

154

Exercise-induced Bronchospasm in Children Effects of Asthma Severity  

Microsoft Academic Search

The prevalence of exercise-induced bronchospasm (EIB) in asthmatic individuals has been reported to vary from 40% to 90%. There are, however, few studies addressing the effects of asthma severity on airway responsiveness to exercise. The purpose of the present study was to investigate the effects of asthma severity on EIB in children. We studied 164 children classified as having intermittent

ANNA LÚCIA B. CABRAL; GLEICE M. CONCEIÇÃO; H. F. FONSECA-GUEDES; MILTON A. MARTINS

155

Detecting Exercise Induced Stress using the Photoplethysmogram Stephen Paul Linder*  

E-print Network

of exercise on the cardiovascular system has been studied extensively using a wide range of physiological1 Detecting Exercise Induced Stress using the Photoplethysmogram Stephen Paul Linder* spl in the photoplethysmographs (PPG) of exercising individuals may be useful for noninvasively detecting hemodynamic stressors

Linder, Stephen

156

The effect of loratadine in exercise-induced asthma  

PubMed Central

Aims: To assess the effect of loratadine in exercise induced asthma. Methods: Randomised, double blind, placebo controlled study of 10 mg oral loratadine, once daily for three days in 11 children. At the end of the treatment period FEV1 was measured, and patients were exercised on a treadmill. FEV1 measurements were repeated at intervals after exercise. Results: Loratadine significantly reduced the decrease in FEV1 after exercise at two, five, 10, 15, and 30 minutes, compared with placebo (p < 0.05). However, the mean decrease in FEV1 at five minutes was more than 15% of baseline in the loratadine group. Conclusions: Loratadine reduces, but does not prevent, exercise induced asthma in children. PMID:11806881

Baki, A; Orhan, F

2002-01-01

157

Effects of thiamine supplementation on exercise-induced fatigue.  

PubMed

High-dose thiamine (vitamin B1) supplementation (100 mg/day) may be helpful in preventing or accelerating recovery from exercise-induced fatigue. Sixteen volunteer male athletes volunteer, 8 with a blood thiamine level of 40 ng/ml or more (normal thiamine group) and 8 with levels below that level (low thiamine group) were selected as subjects. They exercised on a bicycle ergometer and the effects of thiamine supplementation were compared with placebo. Blood thiamine level markedly increased following supplementation of thiamine for 3 days before exercise. Exercise-induced changes in hemodynamic parameters and cardiopulmonary function indicated the onset of fatigue. Thiamine supplementation significantly suppressed the increase in blood glucose in the normal thiamine group and significantly decreased the number of complaints shortly after exercise in the subjective fatigue assessment of 30 items. PMID:8815395

Suzuki, M; Itokawa, Y

1996-03-01

158

Exercise-induced cardiac troponin elevation: evidence, mechanisms, and implications.  

PubMed

Regular physical exercise is recommended for the primary prevention of cardiovascular disease. Although the high prevalence of physical inactivity remains a formidable public health issue, participation in exercise programs and recreational sporting events, such as marathons and triathlons, is on the rise. Although regular exercise training reduces cardiovascular disease risk, recent studies have documented elevations in cardiac troponin (cTn) consistent with cardiac damage after bouts of exercise in apparently healthy individuals. At present, the prevalence, mechanism(s), and clinical significance of exercise-induced cTn release remains incompletely understood. This paper will review the biochemistry, prevalence, potential mechanisms, and management of patients with exercise-induced cTn elevations. PMID:20620736

Shave, Rob; Baggish, Aaron; George, Keith; Wood, Malissa; Scharhag, Jurgen; Whyte, Gregory; Gaze, David; Thompson, Paul D

2010-07-13

159

Exercise-Induced Deep Vein Thrombosis of the Upper Extremity  

Microsoft Academic Search

Upper-extremity deep venous thrombosis (UEDVT) is an increasingly important clinical problem in children. These events are classified as primary or secondary, with the latter being the most common and usually associated with the presence of a central venous line. Among primary UEDVT, the so-called Paget-Schroetter syndrome, effort-related or exercise-induced upper-extremity thrombotic event represents an extremely rare finding that has never

Leonardo R. Brandão; Suzan Williams; Walter H. A. Kahr; Clodagh Ryan; Michael Temple; Anthony K.C. Chan

2006-01-01

160

Exercise-induced phospho-proteins in skeletal muscle  

Microsoft Academic Search

Efforts to identify exercise-induced signaling events in skeletal muscle have been influenced by ground-breaking discoveries in the insulin action field. Initial discoveries demonstrating that exercise enhances insulin sensitivity raised the possibility that contraction directly modulates insulin receptor signaling events. Although the acute effects of exercise on glucose metabolism are clearly insulin-independent, the canonical insulin signaling cascade has been used as

A S Deshmukh; J A Hawley; J R Zierath; JR Zierath

2008-01-01

161

Exercise?Induced growth hormone during acute sleep deprivation  

PubMed Central

Abstract The effect of acute (24?h) sleep deprivation on exercise?induced growth hormone (GH) and insulin?like growth factor?1 (IGF?1) was examined. Ten men (20.6 ± 1.4 years) completed two randomized 24?h sessions including a brief, high?intensity exercise bout following either a night of sleep (SLEEP) or (24?h) sleep deprivation (SLD). Anaerobic performance (mean power [MP], peak power [PP], minimum power [MinP], time to peak power [TTPP], fatigue index, [FI]) and total work per sprint [TWPS]) was determined from four maximal 30?sec Wingate sprints on a cycle ergometer. Self?reported sleep 7 days prior to each session was similar between SLEEP and SLD sessions (7.92 ± 0.33 vs. 7.98 ± 0.39 h, P =0.656, respectively) and during the actual SLEEP session in the lab, the total amount of sleep was similar to the 7 days leading up to the lab session (7.72 ± 0.14 h vs. 7.92 ± 0.33 h, respectively) (P =0.166). No differences existed in MP, PP, MinP, TTPP, FI, TWPS, resting GH concentrations, time to reach exercise?induced peak GH concentration (TTP), or free IGF?1 between sessions. GH area under the curve (AUC) (825.0 ± 199.8 vs. 2212.9 ± 441.9 ?g/L*min, P <0.01), exercise?induced peak GH concentration (17.8 ± 3.7 vs. 39.6 ± 7.1 ?g/L, P <0.01) and ?GH (peak GH – resting GH) (17.2 ± 3.7 vs. 38.2 ± 7.3 ?g/L, P <0.01) were significantly lower during the SLEEP versus SLD session. Our results indicate that the exercise?induced GH response was significantly augmented in sleep?deprived individuals. PMID:25281616

Ritsche, Kevin; Nindl, Bradly C.; Wideman, Laurie

2014-01-01

162

Human Mitochondrial Protein Database  

National Institute of Standards and Technology Data Gateway

SRD 131 Human Mitochondrial Protein Database (Web, free access)   The Human Mitochondrial Protein Database (HMPDb) provides comprehensive data on mitochondrial and human nuclear encoded proteins involved in mitochondrial biogenesis and function. This database consolidates information from SwissProt, LocusLink, Protein Data Bank (PDB), GenBank, Genome Database (GDB), Online Mendelian Inheritance in Man (OMIM), Human Mitochondrial Genome Database (mtDB), MITOMAP, Neuromuscular Disease Center and Human 2-D PAGE Databases. This database is intended as a tool not only to aid in studying the mitochondrion but in studying the associated diseases.

163

Plasma norepinephrine in exercise-induced ventricular tachycardia.  

PubMed

The relation between plasma norepinephrine levels and the occurrence of ventricular tachycardia during exercise testing was prospectively evaluated in 17 patients. Ten patients had reproducible ventricular tachycardia exclusively during exercise or recovery, or both; 7 patients had ventricular tachycardia only during ambulatory electrocardiographic monitoring. The two groups did not differ in age, exercise duration, left ventricular ejection fraction at rest, heart rate throughout the exercise protocol, rest QTc interval, change in QTc interval during exercise, the presence of coronary artery disease or exercise-related myocardial ischemia. Furthermore, there was no difference between groups in plasma norepinephrine levels at rest, peak exercise or in the recovery period. Myocardial ischemia was detectable by thallium perfusion scan in only 2 of the 10 patients with exercise-induced ventricular tachycardia. The 10 patients with exercise-induced ventricular tachycardia underwent repeat exercise testing immediately after maximal intravenous beta-adrenergic blockade with propranolol. Although they had no change in exercise duration, ventricular tachycardia did not occur in 9 of these 10 patients. Plasma norepinephrine levels were significantly decreased compared with levels before beta-adrenergic blockade (p less than 0.0002). Thus, plasma norepinephrine levels do not distinguish patients with reproducible exercise-induced ventricular tachycardia from otherwise comparable patients. Propranolol is highly effective in abolishing this arrhythmia and this effect is associated with decreased norepinephrine levels. PMID:3711506

Sokoloff, N M; Spielman, S R; Greenspan, A M; Rae, A P; Porter, R S; Lowenthal, D T; Hakki, A H; Iskandrian, A S; Kay, H R; Horowitz, L N

1986-07-01

164

A time to reap, a time to sow: mitophagy and biogenesis in cardiac pathophysiology.  

PubMed

Balancing mitophagy and mitochondrial biogenesis is essential for maintaining a healthy population of mitochondria and cellular homeostasis. Coordinated interplay between these two forces that govern mitochondrial turnover plays an important role as an adaptive response against various cellular stresses that can compromise cell survival. Failure to maintain the critical balance between mitophagy and mitochondrial biogenesis or homeostatic turnover of mitochondria results in a population of dysfunctional mitochondria that contribute to various disease processes. In this review we outline the mechanics and relationships between mitophagy and mitochondrial biogenesis, and discuss the implications of a disrupted balance between these two forces, with an emphasis on cardiac physiology. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID:25444712

Andres, Allen M; Stotland, Aleksandr; Queliconi, Bruno B; Gottlieb, Roberta A

2015-01-01

165

Mitoribosomal regulation of OXPHOS biogenesis in plants.  

PubMed

The ribosome filter hypothesis posits that ribosomes are not simple non-selective translation machines but may also function as regulatory elements in protein synthesis. Recent data supporting ribosomal filtering come from plant mitochondria where it has been shown that translation of mitochondrial transcripts encoding components of oxidative phosphorylation complexes (OXPHOS) and of mitoribosomes can be differentially affected by alterations in mitoribosomes. The biogenesis of mitoribosome was perturbed by silencing of a gene encoding a small-subunit protein of the mitoribosome in Arabidopsis thaliana. As a consequence, the mitochondrial OXPHOS and ribosomal transcripts were both upregulated, but only the ribosomal proteins were oversynthesized, while the OXPHOS subunits were actually depleted. This finding implies that the heterogeneity of plant mitoribosomes found in vivo could contribute to the functional selectivity of translation under distinct conditions. Furthermore, global analysis indicates that biogenesis of OXPHOS complexes in plants can be regulated at different levels of mitochondrial and nuclear gene expression, however, the ultimate coordination of genome expression occurs at the complex assembly level. PMID:24634672

Janska, Hanna; Kwasniak, Malgorzata

2014-01-01

166

Biogenesis of telomerase ribonucleoproteins  

PubMed Central

Telomerase adds simple-sequence repeats to the ends of linear chromosomes to counteract the loss of end sequence inherent in conventional DNA replication. Catalytic activity for repeat synthesis results from the cooperation of the telomerase reverse transcriptase protein (TERT) and the template-containing telomerase RNA (TER). TERs vary widely in sequence and structure but share a set of motifs required for TERT binding and catalytic activity. Species-specific TER motifs play essential roles in RNP biogenesis, stability, trafficking, and regulation. Remarkably, the biogenesis pathways that generate mature TER differ across eukaryotes. Furthermore, the cellular processes that direct the assembly of a biologically functional telomerase holoenzyme and its engagement with telomeres are evolutionarily varied and regulated. This review highlights the diversity of strategies for telomerase RNP biogenesis, RNP assembly, and telomere recruitment among ciliates, yeasts, and vertebrates and suggests common themes in these pathways and their regulation. PMID:22875809

Egan, Emily D.; Collins, Kathleen

2012-01-01

167

The Curious Question of Exercise-Induced Pulmonary Edema  

PubMed Central

The question of whether pulmonary edema develops during exercise on land is controversial. Yet, the development of pulmonary edema during swimming and diving is well established. This paper addresses the current controversies that exist in the field of exercise-induced pulmonary edema on land and with water immersion. It also discusses the mechanisms by which pulmonary edema can develop during land exercise, swimming, and diving and the current gaps in knowledge that exist. Finally, this paper discusses how these fields can continue to advance and the areas where clinical knowledge is lacking. PMID:21660232

Bates, Melissa L.; Farrell, Emily T.; Eldridge, Marlowe W.

2011-01-01

168

Sedentary aging increases resting and exercise-induced intramuscular free radical formation  

PubMed Central

Mitochondrial free radical formation has been implicated as a potential mechanism underlying degenerative senescence, although human data are lacking. Therefore, the present study was designed to examine if resting and exercise-induced intramuscular free radical-mediated lipid peroxidation is indeed increased across the spectrum of sedentary aging. Biopsies were obtained from the vastus lateralis in six young (26 ± 6 yr) and six aged (71 ± 6 yr) sedentary males at rest and after maximal knee extensor exercise. Aged tissue exhibited greater (P < 0.05 vs. the young group) electron paramagnetic resonance signal intensity of the mitochondrial ubisemiquinone radical both at rest (+138 ± 62%) and during exercise (+143 ± 40%), and this was further complemented by a greater increase in ?-phenyl-tert-butylnitrone adducts identified as a combination of lipid-derived alkoxyl-alkyl radicals (+295 ± 96% and +298 ± 120%). Lipid hydroperoxides were also elevated at rest (0.190 ± 0.169 vs. 0.148 ± 0.071 nmol/mg total protein) and during exercise (0.567 ± 0.259 vs. 0.320 ± 0.263 nmol/mg total protein) despite a more marked depletion of ascorbate and uptake of ?/?-carotene, retinol, and lycopene (P < 0.05 vs. the young group). The impact of senescence was especially apparent when oxidative stress biomarkers were expressed relative to the age-related decline in mitochondrial volume density and absolute power output at maximal exercise. In conclusion, these findings confirm that intramuscular free radical-mediated lipid peroxidation is elevated at rest and during acute exercise in aged humans. PMID:20507973

McEneny, Jane; Mathieu-Costello, Odile; Henry, Robert R.; James, Philip E.; McCord, Joe M.; Pietri, Sylvia; Young, Ian S.; Richardson, Russell S.

2010-01-01

169

Molecular Genetics of Mitochondrial Disorders  

ERIC Educational Resources Information Center

Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

Wong, Lee-Jun C.

2010-01-01

170

Exercise-Induced Oxidative Stress and Dietary Antioxidants  

PubMed Central

Context: Overproduction of reactive oxygen and nitrogen species during physical exercise, exercise induced oxidative stress and antioxidant supplementation is interesting and controversial concepts that have been considered during the past decades. Evidence Acquisition: In this review, we aimed to summarize current evidence in relation to antioxidant supplementation outcomes during exercise and physical activity. For this aim, we obtained relevant articles through searches of the Medline and PubMed databases between 1980 to 2013. Although major studies have indicated that antioxidants could attenuate biomarkers of exercise-induced oxidative stress and the use of antioxidant supplement is a common phenomenon among athletes and physically active people, there are some doubts regarding the benefits of these. Results: It seems that the best recommendations regarding antioxidants and exercise are having a balanced diet rich in natural antioxidants and phytochemicals. Conclusions: Regular consumption of various fresh fruits and vegetables, whole grains, legumes and beans, sprouts and seeds is an effective and safe way to meet all antioxidant requirements in physically active persons and athletes.

Yavari, Abbas; Javadi, Maryam; Mirmiran, Parvin; Bahadoran, Zahra

2015-01-01

171

Exercise-Induced Anaphylaxis: An Update on Diagnosis and Treatment  

PubMed Central

Exercise-induced anaphylaxis (EIA) and food-dependent, exercise-induced anaphylaxis (FDEIA) are rare but potentially life-threatening clinical syndromes in which association with exercise is crucial. The range of triggering physical activities is broad, including as mild an effort as a stroll. EIA is not fully repeatable (ie, the same exercise may not always result in anaphylaxis in a given patient). In FDEIA, the combined ingestion of sensitizing food and exercise is necessary to precipitate symptoms. Clinical features and management do not differ significantly from other types of anaphylaxis. The pathophysiology of EIA and FDEIA is not fully understood. Different hypotheses concerning the possible influence of exercise on the development of anaphylactic symptoms are taken into consideration. These include increased gastrointestinal permeability, blood flow redistribution, and most likely increased osmolality. This article also describes current diagnostic and therapeutic possibilities, including changes in lifestyle and preventive properties of antiallergic drugs as well as acute treatment of these dangerous syndromes. PMID:20922508

Barg, Wojciech; Medrala, Wojciech

2010-01-01

172

Exercise-induced cardiac performance in autoimmune (type 1) diabetes is associated with a decrease in myocardial diacylglycerol.  

PubMed

One of the fundamental biochemical defects underlying the complications of diabetic cardiovascular system is elevation of diacylglycerol (DAG) and its effects on protein kinase C (PKC) signaling. It has been noted that exercise training attenuates poor cardiac performance in Type 1 diabetes. However, the role of PKC signaling in exercise-induced alleviation of cardiac abnormalities in diabetes is not clear. We investigated the possibility that exercise training modulates PKC-?II signaling to elicit its beneficial effects on the diabetic heart. bio-breeding diabetic resistant rats, a model reminiscent of Type 1 diabetes in humans, were randomly assigned to four groups: 1) nonexercised nondiabetic (NN); 2) nonexercised diabetic (ND); 3) exercised nondiabetic; and 4) exercised diabetic. Treadmill training was initiated upon the onset of diabetes. At the end of 8 wk, left ventricular (LV) hemodynamic assessment revealed compromised function in ND compared with the NN group. LV myocardial histology revealed increased collagen deposition in ND compared with the NN group, while electron microscopy showed a reduction in the viable mitochondrial fraction. Although the PKC-?II levels and activity were unchanged in the diabetic heart, the DAG levels were increased. With exercise training, the deterioration of LV structure and function in diabetes was attenuated. Notably, improved cardiac performance in training was associated with a decrease in myocardial DAG levels in diabetes. Exercise-induced benefits on cardiac performance in diabetes may be mediated by prevention of an increase in myocardial DAG levels. PMID:22797313

Loganathan, Rajprasad; Novikova, Lesya; Boulatnikov, Igor G; Smirnova, Irina V

2012-09-01

173

Short and longer-term effects of creatine supplementation on exercise induced muscle damage  

Microsoft Academic Search

The purpose of this investigation was to determine if creatine supplementation assisted with reducing the amount of exercise induced muscle damage and if creatine supplementation aided in recovery from exercise induced muscle damage. Two groups of subjects (group 1 = creatine; group 2 = placebo) participated in an eccentric exercise protocol following 7 and 30 days of creatine or placebo

John Rosene; Tracey Matthews; Christine Ryan; Keith Belmore; Alisa Bergsten; Jill Blaisdell; James Gaylord; Rebecca Love; Michael Marrone; Kristine Ward; Eric Wilson

2009-01-01

174

Familial Paroxysmal Exercise-Induced Dystonia: Atypical Presentation of Autosomal Dominant GTP-Cyclohydrolase 1 Deficiency  

ERIC Educational Resources Information Center

Paroxysmal exercise-induced dystonia (PED) is one of the rarer forms of paroxysmal dyskinesia, and can occur in sporadic or familial forms. We report a family (male index case, mother and maternal grandfather) with autosomal dominant inheritance of paroxysmal exercise-induced dystonia. The dystonia began in childhood and was only ever induced…

Dale, Russell C.; Melchers, Anna; Fung, Victor S. C.; Grattan-Smith, Padraic; Houlden, Henry; Earl, John

2010-01-01

175

Exploring the Relationship between Exercise-Induced Arousal and Cognition Using Fractionated Response Time  

ERIC Educational Resources Information Center

Although a generally positive effect of acute exercise on cognitive performance has been demonstrated, the specific nature of the relationship between exercise-induced arousal and cognitive performance remains unclear. This study was designed to identify the relationship between exercise-induced arousal and cognitive performance for the central…

Chang, Yu-Kai; Etnier, Jennifer L.; Barella, Lisa A.

2009-01-01

176

Advances in the diagnosis of exercise-induced bronchoconstriction.  

PubMed

Exercise-induced bronchoconstriction (EIB) describes the post exercise phenomenon of acute airway narrowing in association with physical activity. A high prevalence of EIB is reported in both athletic and recreationally active populations. Without treatment, EIB has the potential to impact upon both health and performance. It is now acknowledged that clinical assessment alone is insufficient as a sole means of diagnosing airway dysfunction due to the poor predictive value of symptoms. Furthermore, a broad differential diagnosis has been established for EIB, prompting the requirement of objective evidence of airway narrowing to secure an accurate diagnosis. This article provides an appraisal of recent advances in available methodologies, with the principle aim of optimising diagnostic assessment, treatment and overall clinical care. PMID:24552653

Price, Oliver J; Hull, James H; Ansley, Les

2014-04-01

177

Exercise-induced anaphylaxis as a manifestation of cholinergic urticaria.  

PubMed

Two patients presented with a history of exercise-induced hypotension associated with severe pruritus and either generalized urticaria or facial angioedema. Each patient was exercised under controlled conditions with use of bicycle ergometer exerciser (900 KPM/min) for 20 to 30 min at 23 degrees C. Each patients complained of generalized pruritus and then erupted in lesions typical of cholinergic urticaria. In one patient the lesions became confluent about the face and were followed by eyelid edema, lip swelling, and transient hypotension. Plasma histamine levels were elevated in each patient and reached a maximal level between 20 and 25 min. Neither patient had a change in forced expiratory volume in one second during the episode and detailed pulmonary function testing in one patient revealed no change in airway resistance, specific conductance, forced expiratory vital capacity, or forced expiratory flow rates. One patient had a positive methacholine chloride (Mecholyl) skin test with satellite lesions, and the second patient was skin-test negative. The skin test-positive patient, who was not hypotensive when initially challenged, was strenuously exercised for 15 min/day. Progressively less severe reactions were seen associated with diminished histamine release, and the patient is now on a daily exercise program; symptoms in the second patient are controlled with hydroxazine. Our results indicate that some patients with the exercise-induced anaphylactic syndrome are unusual examples of severe cholinergic urticaria. Furthermore, the utility of a regular exercise program as part of the management of some patients with cholinergic urticaria requires further investigation. PMID:6169753

Kaplan, A P; Natbony, S F; Tawil, A P; Fruchter, L; Foster, M

1981-10-01

178

Biogenesis and Assembly of Eukaryotic Cytochrome c Oxidase Catalytic Core  

PubMed Central

Eukaryotic cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial respiratory chain. COX is a multimeric enzyme formed by subunits of dual genetic origin which assembly is intricate and highly regulated. The COX catalytic core is formed by three mitochondrial DNA encoded subunits, Cox1, Cox2 and Cox3, conserved in the bacterial enzyme. Their biogenesis requires the action of messenger-specific and subunit-specific factors which facilitate the synthesis, membrane insertion, maturation or assembly of the core subunits. The study of yeast strains and human cell lines from patients carrying mutations in structural subunits and COX assembly factors has been invaluable to identify these ancillary factors. Here we review the current state of knowledge of the biogenesis and assembly of the eukaryotic COX catalytic core and discuss the degree of conservation of the players and mechanisms operating from yeast to human. PMID:21958598

Soto, Ileana C.; Fontanesi, Flavia; Liu, Jingjing; Barrientos, Antoni

2011-01-01

179

Peroxisome Biogenesis and Function  

PubMed Central

Peroxisomes are small and single membrane-delimited organelles that execute numerous metabolic reactions and have pivotal roles in plant growth and development. In recent years, forward and reverse genetic studies along with biochemical and cell biological analyses in Arabidopsis have enabled researchers to identify many peroxisome proteins and elucidate their functions. This review focuses on the advances in our understanding of peroxisome biogenesis and metabolism, and further explores the contribution of large-scale analysis, such as in sillco predictions and proteomics, in augmenting our knowledge of peroxisome function In Arabidopsis. PMID:22303249

Kaur, Navneet; Reumann, Sigrun; Hu, Jianping

2009-01-01

180

BIOGENESIS OF MITOCHONDRIA  

PubMed Central

Growth under conditions of oxygen restriction results in a generalized decrease in the definition of the mitochondrial membranes, a decrease in the mitochondrial cytochromes, and a decrease in citric acid cycle enzymes of the obligate aerobic yeast Candida parapsilosis. Addition of unsaturated fatty acids and ergosterol to cultures exposed to limited oxygen results in improved definition of the mitochondrial membranes and an increase in the total mitochondrial cytochrome content of the cells. Euflavine completely inhibits mitochondrial protein synthesis in vitro. Its in vivo effect is to cause the formation of giant mitochondrial profiles with apparently intact outer membranes and modified internal membranes; the cristae (in-folds) appear only as apparently disorganized remnants while the remainder of the inner membrane seems intact. Cytochromes a, a3, b, and c1 are not synthesized by the cells in the presence of euflavine. Ethidium appears to have effects identical to those of euflavine, whereas chloramphenicol, lincomycin, and erythromycin have similar effects in principle but they are less marked. The effects of all the inhibitors are freely reversible after removal of the drugs. The results are discussed in terms of a functionally three-membrane model of the mitochondrion. In addition, the phylogenetic implications of the observed differences between this organism and the facultative anaerobic yeasts are considered. PMID:5792327

Kellerman, G. M.; Biggs, D. R.; Linnane, Anthony W.

1969-01-01

181

Resistance to exercise-induced weight loss: compensatory behavioral adaptations  

PubMed Central

In many interventions that are based on an exercise program intended to induce weight loss, the mean weight loss observed is modest and sometimes far less than the individual expected. The individual responses are also widely variable, with some individuals losing a substantial amount of weight, others maintaining weight, and a few actually gaining weight. The media have focused on the sub-population that loses little weight, contributing to a public perception that exercise has limited utility to cause weight loss. The purpose of the symposium was to present recent, novel data that help explain how compensatory behaviors contribute to a wide discrepancy in exercise-induced weight loss. The presentations provide evidence that some individuals adopt compensatory behaviors, i.e. increased energy intake and/or reduced activity, that offset the exercise energy expenditure and limit weight loss. The challenge for both scientists and clinicians is to develop effective tools to identify which individuals are susceptible to such behaviors, and to develop strategies to minimize their impact. PMID:23470300

Melanson, Edward L.; Keadle, Sarah Kozey; Donnelly, Joseph E.; Braun, Barry; King, Neil A.

2013-01-01

182

Exercise-induced muscle damage and running economy in humans.  

PubMed

Running economy (RE), defined as the energy demand for a given velocity of submaximal running, has been identified as a critical factor of overall distance running performance. Plyometric and resistance trainings, performed during a relatively short period of time (~15-30 days), have been successfully used to improve RE in trained athletes. However, these exercise types, particularly when they are unaccustomed activities for the individuals, may cause delayed onset muscle soreness, swelling, and reduced muscle strength. Some studies have demonstrated that exercise-induced muscle damage has a negative impact on endurance running performance. Specifically, the muscular damage induced by an acute bout of downhill running has been shown to reduce RE during subsequent moderate and high-intensity exercise (>65% VO?max). However, strength exercise (i.e., jumps, isoinertial and isokinetic eccentric exercises) seems to impair RE only for subsequent high-intensity exercise (~90% VO?max). Finally, a single session of resistance exercise or downhill running (i.e., repeated bout effect) attenuates changes in indirect markers of muscle damage and blunts changes in RE. PMID:23431253

Assumpção, Cláudio de Oliveira; Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Greco, Camila Coelho; Denadai, Benedito Sérgio

2013-01-01

183

Combination of the loss of cmnm5U34 with the lack of s2U34 modifications of tRNALys, tRNAGlu and tRNAGln altered mitochondrial biogenesis and respiration  

PubMed Central

Yeast Saccharomyces cerevisiae MTO2, MTO1 and MSS1 genes encoded highly conserved tRNA modifying enzymes for the biosynthesis of cmnm5s2U34 in mitochondrial tRNALys, tRNAGlu and tRNAGln. In fact, Mto1p and Mss1p are involved in the biosynthesis of the cmnm5 group (cmnm5U34), while Mto2p is responsible for the 2-thiouridylation (s2U34) of these tRNAs. Previous studies showed that partial modifications at U34 in mitochondrial tRNA enabled mto1, mto2 and mss1 strains to respire. In this report, we investigated the functional interaction between MTO2, MTO1 and MSS1 genes by using the mto2, mto1 and mss1 single, double and triple mutants. Strikingly, the deletion of MTO2 was synthetically lethal with a mutation of MSS1 or deletion of MTO1 on medium containing glycerol, but not on medium containing glucose. Interestingly, there were no detectable levels of 9 tRNAs including tRNALys, tRNAGlu and tRNAGln in mto2/mss1, mto2/mto1 and mto2/mto1/mss1 strains. Furthermore, mto2/mss1, mto2/mto1 and mto2/mto1/mss1 mutants exhibited extremely low levels of COX1 and CYTB mRNA, 15S and 21S rRNA as well as the complete loss of mitochondrial protein synthesis. The synthetic enhancement combinations likely resulted from the completely abolished modification at U34 of tRNALys, tRNAGlu and tRNAGln, caused by the combination of eliminating the 2-thiouridylation by the mto2 mutation with the absence of the cmnm5U34 by the mto1 or mss1 mutation. The complete loss of modifications at U34 of tRNAs altered mitochondrial RNA metabolisms, causing a degradation of mitochondrial tRNA, mRNA and rRNAs. As a result, failures in mitochondrial RNA metabolisms were responsible for the complete loss of mitochondrial translation. Consequently, defects in mitochondrial protein synthesis caused the instability of their mitochondrial genomes, thus producing the respiratory deficient phenotypes. Therefore, our findings demonstrated a critical role of modifications at U34 of tRNALys, tRNAGlu and tRNAGln in maintenance of mitochondrial genome, mitochondrial RNA stability, translation and respiratory function. PMID:20004207

Wang, Xinjian; Yan, Qingfeng; Guan, Min-Xin

2009-01-01

184

Mitochondrial Therapeutics for Cardioprotection  

PubMed Central

Mitochondria represent approximately one-third of the mass of the heart and play a critical role in maintaining cellular function—however, they are also a potent source of free radicals and pro-apoptotic factors. As such, maintaining mitochondrial homeostasis is essential to cell survival. As the dominant source of ATP, continuous quality control is mandatory to ensure their ongoing optimal function. Mitochondrial quality control is accomplished by the dynamic interplay of fusion, fission, autophagy, and mitochondrial biogenesis. This review examines these processes in the heart and considers their role in the context of ischemia-reperfusion injury. Interventions that modulate mitochondrial turnover, including pharmacologic agents, exercise, and caloric restriction are discussed as a means to improve mitochondrial quality control, ameliorate cardiovascular dysfunction, and enhance longevity. PMID:21718247

Carreira, Raquel S.; Lee, Pamela; Gottlieb, Roberta A.

2013-01-01

185

Exercise-Induced Ischemic Preconditioning and the Potential Application to Cardiac Rehabilitation: A SYSTEMATIC REVIEW.  

PubMed

Exercise-induced ischemic preconditioning (IPC) can be assessed by the results of the second of sequential exercise tests. Exercise-induced IPC is quantified by using the time to 1-mm ST-segment depression, the rate-pressure product at 1-mm ST-segment depression, the maximal ST-segment depression, and the rate-pressure product at the peak of exercise. Few studies reported whether exercise-induced IPC could be used in cardiovascular rehabilitation. A systematic review of the literature limited to human studies was performed using electronic databases, and the main key words were ischemic preconditioning, warm-up phenomenon, and exercise. After careful review, 38 articles were included in the systematic review. This review summarizes the molecular pathways of IPC and describes the first window of protection induced by sequential exercise tests, as well as the effect of medication on exercise-induced IPC. A section on the exercise protocol, mode of exercise, and intensity provides understanding as to what is needed for clinicians to induce IPC with sequential stress tests. The final section of the review is a discussion of the potential use of exercise-induced IPC in a cardiovascular rehabilitation setting. Even if exercise-induced IPC is a well-documented phenomenon, additional studies are needed in order to more fully understand its use in rehabilitation. PMID:25622217

Lalonde, François; Poirier, Paul; Arvisais, Denis; Curnier, Daniel

2015-01-01

186

Air quality and temperature effects on exercise-induced bronchoconstriction.  

PubMed

Exercise-induced bronchoconstriction (EIB) is exaggerated constriction of the airways usually soon after cessation of exercise. This is most often a response to airway dehydration in the presence of airway inflammation in a person with a responsive bronchial smooth muscle. Severity is related to water content of inspired air and level of ventilation achieved and sustained. Repetitive hyperpnea of dry air during training is associated with airway inflammatory changes and remodeling. A response during exercise that is related to pollution or allergen is considered EIB. Ozone and particulate matter are the most widespread pollutants of concern for the exercising population; chronic exposure can lead to new-onset asthma and EIB. Freshly generated emissions particulate matter less than 100 nm is most harmful. Evidence for acute and long-term effects from exercise while inhaling high levels of ozone and/or particulate matter exists. Much evidence supports a relationship between development of airway disorders and exercise in the chlorinated pool. Swimmers typically do not respond in the pool; however, a large percentage responds to a dry air exercise challenge. Studies support oxidative stress mediated pathology for pollutants and a more severe acute response occurs in the asthmatic. Winter sport athletes and swimmers have a higher prevalence of EIB, asthma and airway remodeling than other athletes and the general population. Because of fossil fuel powered ice resurfacers in ice rinks, ice rink athletes have shown high rates of EIB and asthma. For the athlete training in the urban environment, training during low traffic hours and in low traffic areas is suggested. © 2015 American Physiological Society. Compr Physiol 5: 579-610, 2015. PMID:25880506

Rundell, Kenneth W; Anderson, Sandra D; Sue-Chu, Malcolm; Bougault, Valerie; Boulet, Louis-Philippe

2015-03-01

187

Exercise-induced oxidative stress and hypoxic exercise recovery.  

PubMed

Hypoxia due to altitude diminishes performance and alters exercise oxidative stress responses. While oxidative stress and exercise are well studied, the independent impact of hypoxia on exercise recovery remains unknown. Accordingly, we investigated hypoxic recovery effects on post-exercise oxidative stress. Physically active males (n = 12) performed normoxic cycle ergometer exercise consisting of ten high:low intensity intervals, 20 min at moderate intensity, and 6 h recovery at 975 m (normoxic) or simulated 5,000 m (hypoxic chamber) in a randomized counter-balanced cross-over design. Oxygen saturation was monitored via finger pulse oximetry. Blood plasma obtained pre- (Pre), post- (Post), 2 h post- (2Hr), 4 h post- (4Hr), and 6 h (6Hr) post-exercise was assayed for Ferric Reducing Ability of Plasma (FRAP), Trolox Equivalent Antioxidant Capacity (TEAC), Lipid Hydroperoxides (LOOH), and Protein Carbonyls (PC). Biopsies from the vastus lateralis obtained Pre and 6Hr were analyzed by real-time PCR quantify expression of Heme oxygenase 1 (HMOX1), Superoxide Dismutase 2 (SOD2), and Nuclear factor (euthyroid-derived2)-like factor (NFE2L2). PCs were not altered between trials, but a time effect (13 % Post-2Hr increase, p = 0.044) indicated exercise-induced blood oxidative stress. Plasma LOOH revealed only a time effect (p = 0.041), including a 120 % Post-4Hr increase. TEAC values were elevated in normoxic recovery versus hypoxic recovery. FRAP values were higher 6Hr (p = 0.045) in normoxic versus hypoxic recovery. Exercise elevated gene expression of NFE2L2 (20 % increase, p = 0.001) and SOD2 (42 % increase, p = 0.003), but hypoxic recovery abolished this response. Data indicate that recovery in a hypoxic environment, independent of exercise, may alter exercise adaptations to oxidative stress and metabolism. PMID:24384982

Ballmann, Christopher; McGinnis, Graham; Peters, Bridget; Slivka, Dustin; Cuddy, John; Hailes, Walter; Dumke, Charles; Ruby, Brent; Quindry, John

2014-04-01

188

Screening for Exercise-Induced Bronchoconstriction in College Athletes  

PubMed Central

Objective Previous studies have reported that the prevalence of exercise-induced bronchoconstriction (EIB) in athletes is higher than that of the general population. There is increasing evidence that athletes fail to recognize and report symptoms of EIB. As a result, there has been debate whether athletes should be screened for EIB, particularly in high-risk sports. Methods We prospectively studied 144 athletes from six different varsity sports at a large National Collegiate Athletic Association Division I collegiate athletic program. Baseline demographics and medical history were obtained and the presence of asthma symptoms during exercise was documented. Each athlete subsequently underwent a eucapnic voluntary hyperventilation (EVH) test to document the presence of EIB. Exhaled nitric oxide (eNO) quantification was performed immediately before EVH testing. EIB was defined as a ?10% decline in forced expiratory volume in 1 second compared with baseline. Results Only 4 of 144 (2.7%) athletes were EIB-positive after EVH testing. The presence of symptoms was not predictive of EIB as only 2 of the 64 symptomatic athletes (3%) were EIB-positive based on EVH testing. Two of the four athletes who were found to be EIB-positive denied such symptoms. The mean baseline eNO in the four EIB-positive athletes was 13.25 parts per billion (ppb) and 24.5 ppb in the EIB-negative athletes. Conclusions Our data argue that screening for EIB is not recommended given the surprisingly low prevalence of EIB in the population we studied. In addition, the presence or absence of symptoms was not predictive of EIB and eNO testing was not effective in predicting EIB. PMID:22276571

Parsons, Jonathan P.; Cosmar, David; Phillips, Gary; Kaeding, Christopher; Best, Thomas M.; Mastronarde, John G.

2013-01-01

189

Iron-sulfur clusters: biogenesis, molecular mechanisms, and their functional significance.  

PubMed

Iron-sulfur clusters [Fe-S] are small, ubiquitous inorganic cofactors representing one of the earliest catalysts during biomolecule evolution and are involved in fundamental biological reactions, including regulation of enzyme activity, mitochondrial respiration, ribosome biogenesis, cofactor biogenesis, gene expression regulation, and nucleotide metabolism. Although simple in structure, [Fe-S] biogenesis requires complex protein machineries and pathways for assembly. [Fe-S] are assembled from cysteine-derived sulfur and iron onto scaffold proteins followed by transfer to recipient apoproteins. Several predominant iron-sulfur biogenesis systems have been identified, including nitrogen fixation (NIF), sulfur utilization factor (SUF), iron-sulfur cluster (ISC), and cytosolic iron-sulfur protein assembly (CIA), and many protein components have been identified and characterized. In eukaryotes ISC is mainly localized to mitochondria, cytosolic iron-sulfur protein assembly to the cytosol, whereas plant sulfur utilization factor is localized mainly to plastids. Because of this spatial separation, evidence suggests cross-talk mediated by organelle export machineries and dual targeting mechanisms. Although research efforts in understanding iron-sulfur biogenesis has been centered on bacteria, yeast, and plants, recent efforts have implicated inappropriate [Fe-S] biogenesis to underlie many human diseases. In this review we detail our current understanding of [Fe-S] biogenesis across species boundaries highlighting evolutionary conservation and divergence and assembling our knowledge into a cellular context. PMID:20812788

Xu, Xiang Ming; Møller, Simon Geir

2011-07-01

190

Reciprocal ST-segment depression associated with exercise-induced ST-segment elevation indicates residual viability after myocardial infarction  

Microsoft Academic Search

OBJECTIVESWe evaluated the clinical significance of reciprocal ST-segment depression associated with exercise-induced ST-segment elevation for detecting residual viability within the infarcted area.BACKGROUNDAlthough the relation between residual viability and exercise-induced ST-segment elevation has been described, there are no reports focusing on the relation between myocardial viability and reciprocal ST-segment depression associated with exercise-induced ST-segment elevation.METHODSWe evaluated regional blood flow and glucose

Akira Nakano; Jong-Dae Lee; Hiromasa Shimizu; Tatsuro Tsuchida; Yoshiharu Yonekura; Yasushi Ishii; Takanori Ueda

1999-01-01

191

Minimum level of jumping exercise required to maintain exercise-induced bone gains in female rats  

Microsoft Academic Search

Summary  This study determines the minimum level of exercise required to maintain 8 weeks of jumping exercise-induced bone gains in\\u000a rats. It was found that the minimum level of exercise required for maintaining the different exercise-induced bone gains varied\\u000a between 11% and 18% of the initial exercise intensity.\\u000a \\u000a \\u000a \\u000a Introduction  This study ascertains the minimum level of follow-up exercise required to maintain bone gains

F. K. Ooi; R. Singh; H. J. Singh; Y. Umemura

2009-01-01

192

Exercise training and immune crosstalk in breast cancer microenvironment: exploring the paradigms of exercise-induced immune modulation and exercise-induced myokines  

PubMed Central

Observational research suggests that exercise may reduce the risk of breast cancer and improve survival. One proposed mechanism for the protective effect of aerobic exercise related to cancer risk and outcomes, but has not been examined definitively, is the immune response to aerobic exercise. Two prevailing paradigms are proposed. The first considers the host immune response as modifiable by aerobic exercise training. This exercise-modulated immune-tumor crosstalk in the mammary microenvironment may alter the balance between tumor initiation and progression versus tumor suppression. The second paradigm considers the beneficial role of exercise-induced, skeletal muscle-derived cytokines, termed “myokines”. These myokines exert endocrine-like effects on multiple organs, including the mammary glands. In this systematic review, we i) define the role of macrophages and T-cells in breast cancer initiation and progression; ii) address the two paradigms that support exercise-induced immunomodulation; iii) systematically assessed the literature for exercise intervention that assessed biomarkers relevant to both paradigms in human intervention trials of aerobic exercise training, in healthy women and women with breast cancer; iv) incorporated pre-clinical animal studies and non-RCTs for background discussion of putative mechanisms, through which aerobic exercise training modulates the immunological crosstalk, or the myokine-tumor interaction in the tumor microenvironment; and v) speculated on the potential biomarkers and mechanisms that define an exercise-induced, anti-tumor “signature”, with a view toward developing relevant biomarkers for future aerobic exercise intervention trials. PMID:25360210

Goh, Jorming; Niksirat, Negin; Campbell, Kristin L

2014-01-01

193

Chronic exercise-induced compartment pressure elevation measured with a miniaturized fluid pressure monitorA laboratory and clinical study  

Microsoft Academic Search

Increased pressure within an osteofascial compartment may produce a compartment syndrome, one of the principal causes of circulatory compromise in acute traumatic and chronic exercise-induced elevated com partment pressure. Acute and chronic diagnostic quan titation of compartment pressures are a valuable ad junct to clinical diagnosis, particularly when used to evaluate the athlete with exercise-induced pain. This study evaluated a

Brian J. Awbrey; Paul S. Sienkiewicz; Henry J. Mankin

1988-01-01

194

[Mitochondrial disease and mitochondrial DNA depletion syndromes].  

PubMed

Mitochondria is an intracellular double membrane-bound structure and it can provide energy for intracellular metabolism. The metabolism includes Krebs cycle, beta-oxidation and lipid synthesis. The density of mitochondria is different in various tissues dependent upon the demands of oxidative phosphorylation. Mitochondrial diseases can occur by defects either in mitochondrial DNA or nuclear DNA. Human mitochondrial DNA (mtDNA) encoding for 22 tRNAs, 2 rRNAs and 13 mRNAs that are translated in the mitochondria. Mitochondrial genetic diseases are most resulted from defects in the mtDNA which may be point mutations, deletions, or mitochondrial DNA depletion. These patterns of inheritance in mitochondrial diseases include sporadic, maternally inherited, or of Mendelian inheritance. Mitochondrial DNA depletion is caused by defects in the nuclear genes that are responsible for maintenance of integrity of mtDNA or deoxyribonucelotide pools and mtDNA biogenesis. The mtDNA depletion syndrome (MDS) includes the following categories: progressive external ophthalmoplegia (PEO), predominant myopathy, mitochondrial neurogastrointestinal encephalomyopathy (MNGIE), sensory-ataxic neuropathy, dysarthria, and ophthalmoplegia (SANDO) and hepato-encephalopathy. The most common tissues or organs involved in MDS and related disorders include the brain, liver and muscles. These involved genes are divided into two groups including 1) DNA polymerase gamma (POLG, POLG2) and Twinkle genes whose products function directly at the mtDNA replication fork, and 2) adenine nucleotide translocator 1, thymidine phosphorylase, thymidine kinase 2, deoxyguanosine kinase, ADP-forming succinyl-CoA synthetase ligase, MPV17 whose products supply the mitochondria with deoxyribonucleotide triphosphate pools needed for mtDNA replication, and possible mutation in the RRM2B gene. The development has provided new information about the importance of the biosynthetic pathway of the nucleotides for mtDNA replication. Further investigation on the understatanding between the nuclear and mitochondrial genomes is expected. PMID:20329599

Huang, Chin-Chang; Hsu, Chang-Huang

2009-12-01

195

mCSF1, a nucleus-encoded CRM protein required for the processing of many mitochondrial introns, is involved in the biogenesis of respiratory complexes I and IV in Arabidopsis.  

PubMed

The coding regions of many mitochondrial genes in plants are interrupted by intervening sequences that are classified as group II introns. Their splicing is essential for the expression of the genes they interrupt and hence for respiratory function, and is facilitated by various protein cofactors. Despite the importance of these cofactors, only a few of them have been characterized. CRS1-YhbY domain (CRM) is a recently recognized RNA-binding domain that is present in several characterized splicing factors in plant chloroplasts. The Arabidopsis genome encodes 16 CRM proteins, but these are largely uncharacterized. Here, we analyzed the intracellular location of one of these hypothetical proteins in Arabidopsis, mitochondrial CAF-like splicing factor 1 (mCSF1; At4 g31010), and analyzed the growth phenotypes and organellar activities associated with mcsf1 mutants in plants. Our data indicated that mCSF1 resides within mitochondria and its functions are essential during embryogenesis. Mutant plants with reduced mCSF1 displayed inhibited germination and retarded growth phenotypes that were tightly associated with reduced complex I and IV activities. Analogously to the functions of plastid-localized CRM proteins, analysis of the RNA profiles in wildtype and mcsf1 plants showed that mCSF1 acts in the splicing of many of the group II intron RNAs in Arabidopsis mitochondria. PMID:23646912

Zmudjak, Michal; Colas des Francs-Small, Catherine; Keren, Ido; Shaya, Felix; Belausov, Eduard; Small, Ian; Ostersetzer-Biran, Oren

2013-07-01

196

Cellulose biogenesis in Dictyostelium discoideum  

SciTech Connect

Organisms that synthesize cellulose can be found amongst the bacteria, protistans, fungi, and animals, but it is in plants that the importance of cellulose in function (as the major structural constituent of plant cell walls) and economic use (as wood and fiber) can be best appreciated. The structure of cellulose and its biosynthesis have been the subjects of intense investigation. One of the most important insights gained from these studies is that the synthesis of cellulose by living organisms involves much more than simply the polymerization of glucose into a (1{r_arrow}4)-{beta}-linked polymer. The number of glucoses in a polymer (the degree of polymerization), the crystalline form assumed by the glucan chains when they crystallize to form a microfibril, and the dimensions and orientation of the microfibrils are all subject to cellular control. Instead of cellulose biosynthesis, a more appropriate term might be cellulose biogenesis, to emphasize the involvement of cellular structures and mechanisms in controlling polymerization and directing crystallization and deposition. Dictyostelium discoideum is uniquely suitable for the study of cellulose biogenesis because of its amenability to experimental study and manipulation and the extent of our knowledge of its basic cellular mechanisms (as will be evident from the rest of this volume). In this chapter, I will summarize what is known about cellulose biogenesis in D. discoideum, emphasizing its potential to illuminate our understanding both of D. discoideum development and plant cellulose biogenesis.

Blanton, R.L.

1993-12-31

197

Mitochondrial dysfunction in heart failure  

PubMed Central

Heart failure (HF) is a complex chronic clinical syndrome. Energy deficit is considered to be a key contributor to the development of both cardiac and skeletal myopathy. In HF several components of cardiac and skeletal muscle bioenergetics are altered, such as oxygen availability, substrate oxidation, mitochondrial ATP production, and ATP transfer to the contractile apparatus via the creatine kinase shuttle. This review focuses on alterations in mitochondrial biogenesis and respirasome organization, substrate oxidation coupled with ATP synthesis in the context of their contribution to the chronic energy deficit, and mechanical dysfunction of the cardiac and skeletal muscle in HF. We conclude that HF is associated with decreased mitochondrial biogenesis and function in both heart and skeletal muscle, supporting the concept of a systemic mitochondrial cytopathy. The sites of mitochondrial defects are located within the electron transport and phosphorylation apparatus, and differ with the etiology and progression of HF in the two mitochondrial populations (subsarcolemmal and interfibrillar) of cardiac and skeletal muscle. The roles of adrenergic stimulation, the renin-angiotensin system, and cytokines are evaluated as factors responsible for the systemic energy deficit. We propose a cylic AMP-mediated mechanism by which increased adrenergic stimulation contributes to the mitochondrial dysfunction. PMID:22948484

Rosca, Mariana G.; Hoppel, Charles L.

2013-01-01

198

The effects of exercise-induced muscle damage on maximal intensity intermittent exercise performance  

Microsoft Academic Search

Exercise-induced muscle damage (EIMD) is a common occurrence following activities with a high eccentric component. Alterations to the torque–velocity relationship following EIMD would appear to have serious implications for athletic performance, particularly as they relate to impairment of maximal intensity exercise. However, this has been studied infrequently. The purpose of this study was to assess the effects of EIMD on

Craig Twist; Roger Eston

2005-01-01

199

Exercise-induced oxidative stress and muscle stress protein responses in trotters  

Microsoft Academic Search

Acute exercise induces oxidative stress and heat shock protein (HSP) expression. Information on the protection of stress proteins against oxidant insult and muscle damage during moderate exercise is scanty. We aimed to show how a single bout of moderate exercise affects the markers of oxidative stress and heat shock factor-1 (HSF1; the transcriptional regulator of HSP synthesis), and HSP70, HSP90

Susanna Kinnunen; Seppo Hyyppä; Jani Lappalainen; Niku Oksala; Mika Venojärvi; Chitose Nakao; Osmo Hänninen; Chandan K. Sen; Mustafa Atalay

2005-01-01

200

Green Tea Catechin Consumption Enhances Exercise-Induced Abdominal Fat Loss  

Technology Transfer Automated Retrieval System (TEKTRAN)

Aim: This study evaluated the influence of a green tea catechin beverage on body composition and fat distribution in overweight and obese adults during exercised-induced weight loss. Methods: Participants (N=132) were randomly assigned to receive a 500 mL beverage containing approximately 625 mg of...

201

Exercise induced bronchospasm in Ghana: differences in prevalence between urban and rural schoolchildren  

Microsoft Academic Search

BACKGROUND: As more developing countries adopt a westernised style of living, an increase in the prevalence of asthma can be expected to occur in these areas. A study was undertaken to establish the normal response to exercise in Ghanaian children and to use these normal values to determine the prevalence of exercise induced bronchospasm (EIB) in urban rich (UR), urban

E. O. Addo Yobo; A. Custovic; S. C. Taggart; A. P. Asafo-Agyei; A. Woodcock

1997-01-01

202

Dietary salt alters pulmonary function during exercise in exercise-induced asthmatics  

Microsoft Academic Search

Epidemiological and experimental studies have suggested that dietary salt may play a role in airway responsiveness. We have previously shown that a low salt diet improves and a high salt diet exacerbates post-exercise pulmonary function in individuals with exercise-induced asthma. The aim of this study was to determine the influence of both elevated and restricted salt diets on pulmonary function

Timothy D. Mickleborough; Robert W. Gotshall; Loren Cordain; Martin Lindley

2001-01-01

203

Exercise-induced galanin release facilitated GLUT4 translocation in adipocytes of type 2 diabetic rats  

Microsoft Academic Search

Although galanin has been shown to increase insulin sensitivity in skeletal muscle of rats, there is no literature available about the effect of galanin on Glucose Transporter 4 (GLUT4) translocation from intracellular membrane pools to plasma membranes in adipocytes of type 2 diabetic rats. In the present study M35, a galanin antagonist was used to elucidate whether exercise-induced galanin release

Yan Liang; Shudong Sheng; Penghua Fang; Yinping Ma; Jian Li; Qiaojia Shi; Yumei Sui; Mingyi Shi

204

Thyroid Hormone and Estrogen Regulate Exercise-Induced Growth Hormone Release  

PubMed Central

Growth hormone (GH) regulates whole body metabolism, and physical exercise is the most potent stimulus to induce its secretion in humans. The mechanisms underlying GH secretion after exercise remain to be defined. The aim of this study was to elucidate the role of estrogen and pituitary type 1 deiodinase (D1) activation on exercise-induced GH secretion. Ten days after bilateral ovariectomy, animals were submitted to 20 min of treadmill exercise at 75% of maximum aerobic capacity and tissues were harvested immediately or 30 min after exercise. Non-exercised animals were used as controls. A significant increase in D1 activity occurred immediately after exercise (~60%) in sham-operated animals and GH was higher (~6-fold) 30 min after exercise. Estrogen deficient rats exhibited basal levels of GH and D1 activity comparable to those found in control rats. However, after exercise both D1 activity and serum GH levels were blunted compared to sedentary rats. To understand the potential cause-effect of D1 activation in exercise-induced GH release, we pharmacologically blocked D1 activity by propylthiouracil (PTU) injection into intact rats and submitted them to the acute exercise session. D1 inhibition blocked exercise-induced GH secretion, although basal levels were unaltered. In conclusion, estrogen deficiency impairs the induction of thyroid hormone activating enzyme D1 in the pituitary, and GH release by acute exercise. Also, acute D1 activation is essential for exercise-induced GH response. PMID:25874614

Ignacio, Daniele Leão; da S. Silvestre, Diego H.; Cavalcanti-de-Albuquerque, João Paulo Albuquerque; Louzada, Ruy Andrade

2015-01-01

205

Introduction Exercise-induced arterial hypoxemia (EIAH) is frequent in highly  

E-print Network

in the partial pressure of oxygen in arterial blood (PaO2) or in arterial oxyhemoglobin saturation (SpO2) at both pressure of oxygen in arterial blood (PaO2) was measured after each C and R segment and arterialIntroduction Exercise-induced arterial hypoxemia (EIAH) is frequent in highly trained male

Paris-Sud XI, Université de

206

Effects of swimming training on aerobic capacity and exercise induced bronchoconstriction in children with bronchial asthma  

Microsoft Academic Search

BACKGROUNDA study was undertaken to determine whether swimming training improved aerobic capacity, exercise induced bronchoconstriction (EIB), and bronchial responsiveness to inhaled histamine in children with asthma.METHODSEight children with mild or moderate asthma participated in swimming training every day for six weeks. The intensity of training was individually determined and set at 125% of the child’s lactate threshold (LT), measured using

I Matsumoto; H Araki; K Tsuda; H Odajima; S Nishima; Y Higaki; H Tanaka; M Tanaka; M Shindo

1999-01-01

207

Role of Leukotriene Receptor Antagonists in the Treatment of Exercise-Induced Bronchoconstriction: A Review  

PubMed Central

Asthma is a very common disorder that still causes significant morbidity and mortality. A high percentage of individuals with asthma also experience exercise-induced bronchoconstriction (EIB). This article reviews the current literature and updates the reader on the safety, efficacy, and clinical applications of leukotriene modifiers in the treatment of EIB. PMID:20529226

2005-01-01

208

Increased Protein Maintains Nitrogen Balance during Exercise-Induced Energy Deficit  

Technology Transfer Automated Retrieval System (TEKTRAN)

PURPOSE: This study examined how a high-protein diet affected nitrogen balance and protein turnover during an exercise-induced energy deficit. METHODS: Twenty-two men completed a 4-d (D1-4) baseline period (BL) of an energy balance diet while maintaining usual physical activity level, followed by 7 ...

209

Oral contraceptive use and exercise-induced muscle damage and recovery  

Microsoft Academic Search

Endogenous estrogen appears to attenuate muscle damage in animals; however, similar evidence in humans is not as strong. This investigation tested the hypothesis that women taking oral contraceptives, thereby having higher exogenous estrogen levels, would be more susceptible to damage or have an attenuated recovery from exercise-induced muscle damage. Muscle damage in women taking combined estrogen and progesterone oral contraceptives

Kathleen J Savage; Priscilla M Clarkson

2002-01-01

210

Simple Screening Test for Exercise-Induced Bronchospasm in the Middle School Athlete  

ERIC Educational Resources Information Center

This article recommends and provides results from a simple screening test that could be incorporated into a standardized school evaluation for all children participating in sports and physical education classes. The test can be employed by physical educators utilizing their own gym to identify children who demonstrate signs of exercise-induced

Weiss, Tyler J.; Baker, Rachel H.; Weiss, Jason B.; Weiss, Michelle M.

2013-01-01

211

Treatment of mitochondrial disorders: antioxidants and beyond.  

PubMed

Although mitochondrial disorders are among the most common inherited conditions that cause neurologic impairment, there are currently no U.S. Food and Drug Administration (FDA)-approved medications designed to treat primary mitochondrial disease. This is in part related to the lack of biomarkers to monitor disease status or response to treatment and the paucity of randomized, controlled clinical trials focused on mitochondrial disease therapies. Despite this discouraging historical precedent, a number of new approaches to mitochondrial disease therapy are on the horizon. By studying metabolites central to redox chemistry, investigators are gaining new insights into potential noninvasive biomarkers. Controlled clinical trials designed to study the effects of novel redox-modulating therapies, such as EPI-743, in patients with inherited mitochondrial disease are also underway. Furthermore, several new compounds with potential effects on inner mitochondrial membrane function and mitochondrial biogenesis are in development. Such advances are providing the foundation for a new era in mitochondrial disease therapeutics. PMID:24985754

Enns, Gregory M

2014-09-01

212

Pharmacological approaches to restore mitochondrial function  

PubMed Central

Mitochondrial dysfunction is not only a hallmark of rare inherited mitochondrial disorders, but is also implicated in age-related diseases, including those that affect the metabolic and nervous system, such as type 2 diabetes and Parkinson’s disease. Numerous pathways maintain and/or restore proper mitochondrial function, including mitochondrial biogenesis, mitochondrial dynamics, mitophagy, and the mitochondrial unfolded protein response. New and powerful phenotypic assays in cell-based models, as well as multicellular organisms, have been developed to explore these different aspects of mitochondrial function. Modulating mitochondrial function has therefore emerged as an attractive therapeutic strategy for a range of diseases, which has spurred active drug discovery efforts in this area. PMID:23666487

Andreux, Pénélope A.; Houtkooper, Riekelt H.; Auwerx, Johan

2014-01-01

213

Exercise-induced ischemic preconditioning detected by sequential exercise stress tests: a meta-analysis.  

PubMed

Exercise-induced ischemic preconditioning (IPC) can be assessed with the second exercise stress test during sequential testing. Exercise-induced IPC is defined as the time to 1 mm ST segment depression (STD), the rate-pressure product (RPP) at 1 mm STD, the maximal ST depression and the rate-pressure product at peak exercise. The purpose of this meta-analysis is to validate the parameters used to assess exercise-induced IPC in the scientific community. A literature search was performed using electronic database. The main key words were limited to human studies, which were (a) ischemic preconditioning, (b) warm-up phenomenon, and (c) exercise. Meta-analyses were performed on the study-specific mean difference between the clinical measures obtained in the two consecutive stress tests (second minus first test score). Random effect models were fitted with inverse variance weighting to provide greater weight to studies with larger sample size and more precise estimates. The search resulted in 309 articles of which 34 were included after revision (1053 patients). Results are: (a) time to 1 mm ST segment depression increased by 91 s (95% confidence interval (CI): 75-108), p < 0.001; (b) peak ST depression decreased by -0.38 mm (95% CI: -0.66 to -0.10), p < 0.01; and (c) rate-pressure product at 1 mm STD increased by 1.80 × 10(3)mmHg (95% CI: 1.0-2.0), p < 0.001. This is the first meta-analysis to set clinical parameters to assess the benefit of exercise-induced ischemic preconditioning in sequential stress testing. The results of this first meta-analysis on the sequential stress test confirm what is presented in the literature by independent studies on exercise-induced ischemic preconditioning. From now on, the results could be used in further research to set standardized parameters to assess the phenomenon. PMID:23983070

Lalonde, François; Poirier, Paul; Sylvestre, Marie-Pierre; Arvisais, Denis; Curnier, Daniel

2015-01-01

214

PGC-1alpha/beta induced expression partially compensates for respiratory chain defects in cells from patients with mitochondrial disorders.  

PubMed

Members of the peroxisome proliferator-activated receptor gamma coactivator (PGC) family are potent inducers of mitochondrial biogenesis. We have tested the potential effect of increased mitochondrial biogenesis in cells derived from patients harboring oxidative phosphorylation defects due to either nuclear or mitochondrial DNA mutations. We found that the PGC-1alpha and/or PGC-1beta expression improved mitochondrial respiration in cells harboring a complex III or IV deficiency as well as in transmitochondrial cybrids harboring mitochondrial encephalomyopathy lactic acidosis and stroke A3243G tRNA((Leu)UUR) gene mutation. The respiratory function improvement was found to be associated with increased levels of mitochondrial components per cell, although this increase was not homogeneous. These results reinforce the concept that increased mitochondrial biogenesis is a promising venue for the treatment of mitochondrial diseases. PMID:19297390

Srivastava, Sarika; Diaz, Francisca; Iommarini, Luisa; Aure, Karine; Lombes, Anne; Moraes, Carlos T

2009-05-15

215

Organelle biogenesis and interorganellar connections  

PubMed Central

Membrane contact sites (MCSs) allow the exchange of molecules and information between organelles, even when their membranes cannot fuse directly. In recent years, a number of functions have been attributed to these contacts, highlighting their critical role in cell homeostasis. Although inter-organellar connections typically involve the endoplasmic reticulum (ER), we recently reported the presence of a novel MCSs between melanosomes and mitochondria. Melanosome-mitochondrion contacts appear mediated by fibrillar bridges resembling the protein tethers linking mitochondria and the ER, both for their ultrastructural features and the involvement of Mitofusin 2. The frequency of these connections correlates spatially and timely with melanosome biogenesis, suggesting a functional link between the 2 processes and in general that organelle biogenesis in the secretory pathway requires interorganellar crosstalks at multiple steps. Here, we summarize the different functions attributed to MCSs, and discuss their possible relevance for the newly identified melanosome-mitochondrion liaison. PMID:25346798

Daniele, Tiziana; Schiaffino, Maria Vittoria

2014-01-01

216

Polyphenols in Exercise Performance and Prevention of Exercise-Induced Muscle Damage  

PubMed Central

Although moderate physical exercise is considered an essential component of a healthy lifestyle that leads the organism to adapt itself to different stresses, exercise, especially when exhaustive, is also known to induce oxidative stress, inflammation, and muscle damage. Many efforts have been carried out to identify dietary strategies or micronutrients able to prevent or at least attenuate the exercise-induced muscle damage and stress. Unfortunately most studies have failed to show protection, and at the present time data supporting the protective effect of micronutrients, as antioxidant vitamins, are weak and trivial. This review focuses on those polyphenols, present in the plant kingdom, that have been recently suggested to exert some positive effects on exercise-induced muscle damage and oxidative stress. In the last decade flavonoids as quercetin, catechins, and other polyphenols as resveratrol have caught the scientists attention. However, at the present time drawing a clear and definitive conclusion seems to be untimely. PMID:23983900

Hrelia, Silvana

2013-01-01

217

Ganoderma lucidum polysaccharides supplementation attenuates exercise-induced oxidative stress in skeletal muscle of mice.  

PubMed

The present study was designed to determine the effects of Ganoderma lucidum polysaccharides (GL-PS) on exhaustive exercise-induced oxidative stress in skeletal muscle tissues of mice. The mice were divided into four groups (three GL-PS administered groups and the control group). The control group was administered with distilled water and GL-PS administered groups were administered with GL-PS (50, 100 and 200 mg/kg body weight per day). After 28 days, the mice performed an exhaustive swimming exercise, along with the determination of superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT) activities and malondialdehyde (MDA) levels in the skeletal muscle of mice. The results showed that GL-PS could increase antioxidant enzymes activities and decrease the MDA levels in the skeletal muscle of mice. This study provides strong evidence that GL-PS supplementation possessed protective effects against exhaustive exercise-induced oxidative stress. PMID:24600303

Zhonghui, Zhao; Xiaowei, Zheng; Fang, Fang

2014-04-01

218

Eccentric exercise-induced muscle damage dissociates the lactate and gas exchange thresholds  

Microsoft Academic Search

We tested the hypothesis that exercise-induced muscle damage would increase the ventilatory ([Vdot]E) response to incremental\\/ramp cycle exercise (lower the gas exchange threshold) without altering the blood lactate profile, thereby dissociating the gas exchange and lactate thresholds. Ten physically active men completed maximal incremental cycle tests before (pre) and 48 h after (post) performing eccentric exercise comprising 100 squats. Pulmonary gas

Rosemary C. Davies; Ann V. Rowlands; David C. Poole; Andrew M. Jones; Roger G. Eston

2011-01-01

219

Leg Immersion in Warm Water, Stretch-Shortening Exercise, and Exercise-Induced Muscle Damage  

PubMed Central

Context: Whether muscle warming protects against exercise-induced muscle damage is unknown. Objective: To determine the effect of leg immersion in warm water before stretch-shortening exercise on the time course of indirect markers of exercise-induced muscle damage. Design: Crossover trial. Setting: Human kinetics laboratory. Patients or Other Participants: Eleven healthy, untrained men (age ?=? 21.5 ± 1.7 years). Intervention(s): Participants' legs were immersed in a water bath at 44 ± 1°C for 45 minutes. Main Outcome Measure(s): Creatine kinase changes in the blood, muscle soreness, prolonged (within 72 hours) impairment in maximal voluntary contraction force and height of drop jump, and electrically evoked muscle force at low and high stimulation frequencies at short and long muscle lengths. Results: Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage, including creatine kinase activity in the blood, muscle soreness, maximal voluntary contraction force, and jump height. The values for maximal voluntary contraction force and jump height, however, were higher during prewarming than for the control condition at 48 hours after stretch-shortening exercise, but this difference was only minor at other time points. Muscle prewarming did not bring about any changes in the dynamics of low-frequency fatigue, registered at either short or long muscle length, within 72 hours of stretch-shortening exercise. Conclusions: Leg immersion in warm water before stretch-shortening exercise reduced most of the indirect markers of exercise-induced muscle damage. However, the clinical application of muscle prewarming may be limited, because decreasing muscle damage did not necessarily lead to improved voluntary performance. PMID:19030137

Skurvydas, Albertas; Kamandulis, Sigitas; Stanislovaitis, Aleksas; Streckis, Vytautas; Mamkus, Gediminas; Drazdauskas, Adomas

2008-01-01

220

Initial metabolic state and exercise-induced endotoxaemia are unrelated to gastrointestinal symptoms during exercise  

Microsoft Academic Search

The aim of the study was to investigate the association between the initial metabolic state and exercise-induced endotoxaemia on the appearance of gastrointestinal symptoms (GIS) during exer- cise. Eleven males (36.6 ± 4.9 yrs, 1.7 ± 0.1 m, 74.5 ± 7.7 kg, DEXA body fat % 17.2 ± 6.6, VO2max 57.4 ± 7.4 ml·kg -1 ·min-1) underwent two isoenergetic diets

José Moncada-Jiménez; Eric Plaisance; Michael L. Mestek; Felipe Araya-Ramírez; Lance Ratcliff; James K. Taylor; Peter W. Grandjean; Luis F. AragónVargas

2009-01-01

221

Etiology of exercise-induced asthma: Physical stress-induced transcription  

Microsoft Academic Search

Exercise-induced asthma (EIA) occurs with a high prevalence in both asthmatic and nonasthmatic individuals. Although understanding\\u000a of the functional genomics (proteomics) in sports medicine remains limited, this review focuses on immunologic changes as\\u000a reflected in transcriptional regulation in respect to EIA. Studies demonstrated that leukotrienes play a significant role\\u000a in EIA. Exercise increases the distribution of leukotrienes and influences the

Thomas Hilberg

2007-01-01

222

Prevalence of exercise-induced cough in schoolchildren: a pilot study.  

PubMed

Association between exercise-induced bronchoconstriction (EIB) and physical activity has not been investigated in a natural school environment in a general pediatric population. Our objective was to determine the prevalence of exercise-induced symptoms (cough, wheeze, chest tightness, dyspnea) and bronchospasm among schoolchildren during physical education (PE). A total of 557 schoolchildren from seven public schools were enrolled. Information regarding demographic characteristic, previously diagnosed asthma was obtained. All children attended 45-minute PE lesson with similar exercise intensity. Pulmonary function tests were performed before and immediately after PE lesson. The diagnosis of EIB was defined as a forced expiratory volume in one second (FEV1) decrease from baseline of more than or equal to 10% with exercise. Cough and dyspnea after exercise were recorded. A total of 557 participants were included into the analysis. After PE lesson, 15.3% children suffered from cough, 0.9% reported dyspnea, and 10.1% had more than 10% fall in FEV1 from baseline. Among all participants, 5.9% had doctors' diagnosed asthma, 4.8% of them were treated with inhaled corticosteroids (ICS). Among children with cough, 21.5% had asthma and 17.6% experienced EIB. Among asthmatics, 48.6% suffered from cough and 18.2% had more than 10% fall in FEV1 from baseline after PE lesson. EIB was not affected by age, gender, body mass index, asthma diagnosis, and ICS use. Only cough (odds ratio: 2.21, 95% confidence interval: 1.16-4.23; p = 0.0161) was independently associated with EIB. This study showed a high prevalence of exercise-induced cough and/or 10% fall in FEV1 during activity lesson in a natural school environment in a large urban population of schoolchildren. Our results call for another studies addressing the impact of environment on exercise-induced symptoms. PMID:25562558

Cichalewski, ?ukasz; Majak, Pawe?; Jerzy?ska, Joanna; Stelmach, W?odzimierz; Kaczmarek, Adam; Malewska, Kamila; Smejda, Katarzyna; Stelmach, Iwona

2015-01-01

223

Diagnosis of exercise-induced pain in the anterior aspect of the lower leg  

Microsoft Academic Search

Ninety-eight patients with chronic exercise-induced pain in the anterior compartment of the lower leg under went extensive clinical and laboratory investigations to establish the diagnosis. They all were referred because of a putative chronic compartment syndrome (CCS). Intramuscular pressure was recorded bilaterally during exercise in the anterior tibial muscle in all of them. Conduction-velocity recordings of the deep and super

Jorma Styf

1988-01-01

224

Patient pain drawing in diagnosing the cause of exercise-induced leg pain  

Microsoft Academic Search

IntroductionClassifying symptoms by patient pain drawing (PPD) may be helpful in diagnosing chronic anterior compartment syndrome (CACS). We have investigated the sensitivity and interobserver reliability of the PPD to diagnose CACS among patients with exercise-induced leg pain (EILP).MethodsThis study included 88 consecutive patients (48 men, 40 women; mean age 33, range 13–66, years). Two observers independently diagnosed the causes of

K Rennerfelt; Q Zhang; J Styf

2011-01-01

225

Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction  

Microsoft Academic Search

Background: Montelukast, a leukotriene receptor antagonist, and salmeterol, a long-acting ?2 -receptor agonist, each have demonstrated benefits in the treatment of exercise-induced bronchoconstriction (EIB) in short-term studies. Direct comparisons between these agents in long-term studies are limited. Objective: We sought to compare montelukast and salmeterol in the long-term treatment of EIB. Methods: One hundred ninety-seven patients with mild asthma and

Cesar Villaran; Shane J. O’Neill; Arthur Helbling; Jan A. van Noord; Tak H. Lee; Alexander G. Chuchalin; Stephen J. Langley; Kulasiri A. Gunawardena; Stanislav Suskovic; Martino Laurenzi; Jay Jasan; Joris Menten; Jonathan A. Leff

1999-01-01

226

Frequency of food-dependent, exercise-induced anaphylaxis in Japanese junior-high-school students  

Microsoft Academic Search

Background: Food-dependent, exercise-induced anaphylaxis (FEIAn) is classified among the physical allergies. The pathophysiology of FEIAn remains unknown, as does the frequency of FEIAn in the general population. Objective: We sought to study the epidemiology of FEIAn, especially its frequency in junior-high-school students in Yokohama, Japan. Methods: A questionnaire asking about the occurrence of FEIAn in school students was sent to

Yukoh Aihara; Yuriko Takahashi; Takeshi Kotoyori; Toshihiro Mitsuda; Reiko Ito; Michiko Aihara; Zenro Ikezawa; Shumpei Yokota

2001-01-01

227

[Prolonged effect against exercise-induced bronchospasm: salmeterol versus sodium cromoglycate].  

PubMed

Nineteen subjects with isolated exercise-induced asthma (FEV1, FEF25-75%, PEFR, FVC greater than 95% predicted values, fall in FEV1 of at least 15% after exercise, typical recent symptoms of exercise-induced asthma, no other treatment) were entered in a multicenter trial carried out in a double blind, double placebo, cross-over manner. After a one-month baseline period, subjects underwent an exercise after inhaling 100 micrograms of salmeterol (n = 12) or 40 mg of sodium cromoglycate (n = 7). Treatments were alternated before the second exercise which took place at least 2 days after the first. Efficacy was assessed by examining changes in FEV1, FEF25-75% after exercise carried out 30 minutes and 7 hours after administering the treatment by comparison with baseline values (assessments done 1, 10 and 30 minutes after exercise, lowest of three values kept for the analysis of each parameter). FEV1 and FEF25-75% were significantly higher 30 minutes after taking salmeterol. Salmeterol was found to be superior to sodium cromoglycate for all parameters 7 hours after administering the drug. Both treatments were well tolerated. This study confirms that the longer duration of effect of salmeterol and its superiority by comparison with the standard treatments of exercise-induced asthma. PMID:1350367

Guérin, J C; Brambilla, C; Godard, P; de Muizon, H; Aubert, B; Bons, J

1992-01-01

228

Contribution of endothelium-derived hyperpolarizing factor to exercise-induced vasodilation in health and hypercholesterolemia.  

PubMed

The role of endothelium-derived hyperpolarizing factor (EDHF) in either the healthy circulation or in those with hypercholesterolemia is unknown. In healthy and hypercholesterolemic subjects, we measured forearm blood flow (FBF) using strain-gauge plethysmography at rest, during graded handgrip exercise, and after sodium nitroprusside infusion. Measurements were repeated after l-NMMA, tetraethylammonium (TEA), and combined infusions. At rest, l-NMMA infusion reduced FBF in healthy but not hypercholesterolemic subjects. At peak exercise, vasodilation was lower in hypercholesterolemic compared to healthy subjects (274% vs 438% increase in FBF, p=0.017). TEA infusion reduced exercise-induced vasodilation in both healthy and hypercholesterolemic subjects (27%, p<0.0001 and -20%, p<0.0001, respectively). The addition of l-NMMA to TEA further reduced FBF in healthy (-14%, p=0.012) but not in hypercholesterolemic subjects, indicating a reduced nitric oxide and greater EDHF-mediated contribution to exercise-induced vasodilation in hypercholesterolemia. In conclusion, exercise-induced vasodilation is impaired and predominantly mediated by EDHF in hypercholesterolemic subjects. CLINICAL TRIAL REGISTRATION IDENTIFIER NCT00166166: PMID:25648989

Ozkor, Muhiddin A; Hayek, Salim S; Rahman, Ayaz M; Murrow, Jonathan R; Kavtaradze, Nino; Lin, Ji; Manatunga, Amita; Quyyumi, Arshed A

2015-02-01

229

Exercise-induced asthma: critical analysis of the protective role of montelukast  

PubMed Central

Exercise-induced asthma/exercise-induced bronchospasm (EIA/EIB) is a prevalent and clinically important disease affecting young children through older adulthood. These terms are often used interchangeably and the differences are not clearly defined in the literature. The pathogenesis of EIA/EIB may be different in those with persistent asthma compared to those with exercise-induced symptoms only. The natural history of EIA is unclear and may be different for elite athletes. Leukotriene biology has helped the understanding of EIB. The type and intensity of exercise are important factors for EIB. Exercise participation is necessary for proper development and control of EIA is recommended. Symptoms of EIB should be confirmed by proper testing. Biologic markers may also be helpful in diagnosis. Not all exercise symptoms are from EIB. Many medication and nonpharmacologic treatments are available. Asthma education is an important component of managing EIA. Many medications have been tested and the comparisons are complicated. Montelukast is a US Food and Drug Administration-approved asthma and EIB controller and has a number of potential advantages to other asthma medications including short onset of action, ease of use, and lack of tolerance. Not all patients improve with montelukast and rescue medication should be available. PMID:21437147

Carver, Terrence W

2009-01-01

230

Food-dependent exercise-induced anaphylaxis due to wheat in a young woman.  

PubMed

Food Dependent Exercise-Induced Allergy is a rare condition. However, the occurrence of anaphylaxis is increasing especially in young people. The diagnosis of anaphylaxis is based on clinical criteria and can be supported by laboratory tests such as serum tryptase and positive skin test results for specific IgE to potential triggering allergens. Anaphylaxis prevention needs strict avoidance of confirmed relevant allergen. Food-exercise challenge test may be an acceptable method for diagnosis of Food Dependent Exercise-Induced Allergy and dietary elimination of food is recommended to manage it. In this study, a 32 year-old woman visited the allergy clinic with a history of several episodes of hives since 11 years ago and 3 life-threatening attacks of anaphylaxis during the previous 6 months. The onsets of majority of these attacks were due to physical activity after breakfast. On Blood RAST test, the panel of common food Allergens was used and she had positive test only to wheat flour. On skin prick tests for common food allergens she showed a 6 millimeter wheal with 14 mm flare to Wheat Extract. The rest of allergens were negative.The patient was diagnosed as wheat-dependent exercise-induced, and all foods containing wheat were omitted from her diet. In this report we emphasized on the importance of careful history taking in anaphylaxis diagnosis. PMID:23454785

Ahanchian, Hamid; Farid, Reza; Ansari, Elham; Kianifar, Hamid Reza; Jabbari Azad, Farahzad; Jafari, Seyed Ali; Purreza, Reza; Noorizadeh, Shadi

2013-03-01

231

Acute exercise induces biphasic increase in respiratory mRNA in skeletal muscle  

SciTech Connect

Peroxisome proliferator-activated receptor {gamma} coactivator-1{alpha} (PGC-1{alpha}) promotes the expression of oxidative enzymes in skeletal muscle. We hypothesized that activation of the p38 MAPK (mitogen-activated protein kinase) in response to exercise was associated with exercise-induced PGC-1{alpha} and respiratory enzymes expression and aimed to demonstrate this under the physiological level. We subjected mice to a single bout of treadmill running and found that the exercise induced a biphasic increase in the expression of respiratory enzymes mRNA. The second phase of the increase was accompanied by an increase in PGC-1{alpha} protein, but the other was not. Administration of SB203580 (SB), an inhibitor of p38 MAPK, suppressed the increase in PGC-1{alpha} expression and respiratory enzymes mRNA in both phases. These data suggest that p38 MAPK is associated with the exercise-induced expression of PGC-1{alpha} and biphasic increase in respiratory enzyme mRNAs in mouse skeletal muscle under physiological conditions.

Ikeda, Shin-ichi [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 (Japan); Kizaki, Takako [Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan); Haga, Shukoh [Department of Exercise Physiology, Graduate School of Science, Tokyo Metropolitan University, 1-1 Minami-Osawa, Hachioji, Tokyo 192-0397 (Japan); Ohno, Hideki [Department of Molecular Predictive Medicine and Sport Science, Kyorin University, School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611 (Japan); Takemasa, Tohru [Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-8574 (Japan)], E-mail: takemasa@taiiku.tsukuba.ac.jp

2008-04-04

232

Exercise-induced ST-segment depression in inferior leads during treadmill exercise testing and coronary artery disease  

Microsoft Academic Search

The exercise electrocardiogram is a commonly used non-invasive and inexpensive method for detection of electrocardiogram (ECG) changes secondary to myocardial ischemia. Reversible ST-segment depression is the characteristic finding associated with exercise-induced, demand-driven ischemia in patients with significant coronary obstruction but no flow limitation at rest. The exercise-induced ST-segment depression in inferior leads has been questioned and it has been reported

Salvatore Patanè; Filippo Marte; Giuseppe Dattilo; Rosario Grassi; Francesco Patanè

2010-01-01

233

NAD+-Dependent Activation of Sirt1 Corrects the Phenotype in a Mouse Model of Mitochondrial Disease  

PubMed Central

Summary Mitochondrial disorders are highly heterogeneous conditions characterized by defects of the mitochondrial respiratory chain. Pharmacological activation of mitochondrial biogenesis has been proposed as an effective means to correct the biochemical defects and ameliorate the clinical phenotype in these severely disabling, often fatal, disorders. Pathways related to mitochondrial biogenesis are targets of Sirtuin1, a NAD+-dependent protein deacetylase. As NAD+ boosts the activity of Sirtuin1 and other sirtuins, intracellular levels of NAD+ play a key role in the homeostatic control of mitochondrial function by the metabolic status of the cell. We show here that supplementation with nicotinamide riboside, a natural NAD+ precursor, or reduction of NAD+ consumption by inhibiting the poly(ADP-ribose) polymerases, leads to marked improvement of the respiratory chain defect and exercise intolerance of the Sco2 knockout/knockin mouse, a mitochondrial disease model characterized by impaired cytochrome c oxidase biogenesis. This strategy is potentially translatable into therapy of mitochondrial disorders in humans. PMID:24814483

Cerutti, Raffaele; Pirinen, Eija; Lamperti, Costanza; Marchet, Silvia; Sauve, Anthony A.; Li, Wei; Leoni, Valerio; Schon, Eric A.; Dantzer, Françoise; Auwerx, Johan; Viscomi, Carlo; Zeviani, Massimo

2014-01-01

234

EVALUATION OF THE BIOGENESIS SOIL WASHING TECHNOLOGY  

EPA Science Inventory

The BioGenesis Enterprises, Inc. (BioGenesis) soil washing technology was demonstrated as part of the US Environmental Protection Agency's (EPA) Superfund Innovative Technology Evaluation (SITE) program in November 1992. he demonstration was conducted over three days at a petrole...

235

EVALUATION OF THE BIOGENESIS SOIL WASHING TECHNOLOGY  

EPA Science Inventory

The BioGenesis Enterprises, Inc. (BioGenesis) soil washing technology was demonstrated as part of the US Environmental Protection Agency's (EPA) Superfund Innovative Technology Evaluation (SITE) program in November 1992. The demonstration was conducted over three days at a petrol...

236

MitoTimer: a novel protein for monitoring mitochondrial turnover in the heart.  

PubMed

Mitochondrial quality control refers to the coordinated cellular systems involved in maintaining a population of healthy mitochondria. In addition to mitochondrial protein chaperones (Hsp10, Hsp60, and others) and proteases (Lon, AAA proteases) needed for refolding or degrading individual proteins, mitochondrial integrity is maintained through the regulation of protein import via the TOM/TIM complex and protein redistribution across the network via fusion and fission and through mitophagy and biogenesis, key determinants of mitochondrial turnover. A growing number of studies point to the importance of mitochondrial dynamics (fusion/fission) and mitochondrial autophagy in the heart. Mitochondrial biogenesis must keep pace with mitophagy in order to maintain a stable number of mitochondria. In this review, we will discuss the use of MitoTimer as a tool to monitor mitochondrial turnover. PMID:25479961

Gottlieb, Roberta A; Stotland, Aleksandr

2015-03-01

237

Mitochondrial cholesterol: mechanisms of import and effects on mitochondrial function.  

PubMed

Mitochondria require cholesterol for biogenesis and membrane maintenance, and for the synthesis of steroids, oxysterols and hepatic bile acids. Multiple pathways mediate the transport of cholesterol from different subcellular pools to mitochondria. In steroidogenic cells, the steroidogenic acute regulatory protein (StAR) interacts with a mitochondrial protein complex to mediate cholesterol delivery to the inner mitochondrial membrane for conversion to pregnenolone. In non-steroidogenic cells, several members of a protein family defined by the presence of a StAR-related lipid transfer (START) domain play key roles in the delivery of cholesterol to mitochondrial membranes. Subdomains of the endoplasmic reticulum (ER), termed mitochondria-associated ER membranes (MAM), form membrane contact sites with mitochondria and may contribute to the transport of ER cholesterol to mitochondria, either independently or in conjunction with lipid-transfer proteins. Model systems of mitochondria enriched with cholesterol in vitro and mitochondria isolated from cells with (patho)physiological mitochondrial cholesterol accumulation clearly demonstrate that mitochondrial cholesterol levels affect mitochondrial function. Increased mitochondrial cholesterol levels have been observed in several diseases, including cancer, ischemia, steatohepatitis and neurodegenerative diseases, and influence disease pathology. Hence, a deeper understanding of the mechanisms maintaining mitochondrial cholesterol homeostasis may reveal additional targets for therapeutic intervention. Here we give a brief overview of mitochondrial cholesterol import in steroidogenic cells, and then focus on cholesterol trafficking pathways that deliver cholesterol to mitochondrial membranes in non-steroidogenic cells. We also briefly discuss the consequences of increased mitochondrial cholesterol levels on mitochondrial function and their potential role in disease pathology. PMID:25425472

Martin, Laura A; Kennedy, Barry E; Karten, Barbara

2014-11-26

238

Mitochondrial Homeostasis in Acute Organ Failure  

PubMed Central

The kidneys compose approximately 0.5% of the body mass but consume about 10% of the oxygen in cellular respiration. This discordance is due to the high energy demands on the kidney for reabsorption of filtered blood components and makes the kidney sensitive to mitochondrial stress, the primary source of cellular ATP. Regardless of the etiology, acute kidney injury (AKI) almost always involves aspects of mitochondrial dysfunction. Recent evidence from experimental models suggests that preserving mitochondrial function or promoting mitochondrial repair rescues renal function during AKI. In this review we discuss the effect of AKI on disruption of mitochondrial homeostasis, and how the dynamic processes of mitochondrial biogenesis, fission/fusion, and mitophagy influence renal injury and recovery. PMID:24386614

Stallons, L. Jay; Funk, Jason A.; Schnellmann, Rick G.

2013-01-01

239

Increased Insulin Sensitivity and Distorted Mitochondrial Adaptations during Muscle Unloading  

PubMed Central

We aimed to further investigate mitochondrial adaptations to muscle disuse and the consequent metabolic disorders. Male rats were submitted to hindlimb unloading (HU) for three weeks. Interestingly, HU increased insulin sensitivity index (ISI) and decreased blood level of triglyceride and insulin. In skeletal muscle, HU decreased expression of pyruvate dehydrogenase kinase 4 (PDK4) and its protein level in mitochondria. HU decreased mtDNA content and mitochondrial biogenesis biomarkers. Dynamin-related protein (Drp1) in mitochondria and Mfn2 mRNA level were decreased significantly by HU. Our findings provide more extensive insight into mitochondrial adaptations to muscle disuse, involving the shift of fuel utilization towards glucose, the decreased mitochondrial biogenesis and the distorted mitochondrial dynamics. PMID:23443131

Qi, Zhengtang; Zhang, Yuan; Guo, Wei; Ji, Liu; Ding, Shuzhe

2012-01-01

240

Mitochondrial alteration in type 2 diabetes and obesity  

PubMed Central

The growing epidemic of type 2 diabetes mellitus (T2DM) and obesity is largely attributed to the current lifestyle of over-consumption and physical inactivity. As the primary platform controlling metabolic and energy homeostasis, mitochondria show aberrant changes in T2DM and obese subjects. While the underlying mechanism is under extensive investigation, epigenetic regulation is now emerging to play an important role in mitochondrial biogenesis, function, and dynamics. In line with lifestyle modifications preventing mitochondrial alterations and metabolic disorders, exercise has been shown to change DNA methylation of the promoter of PGC1? to favor gene expression responsible for mitochondrial biogenesis and function. In this article we discuss the epigenetic mechanism of mitochondrial alteration in T2DM and obesity, and the effects of lifestyle on epigenetic regulation. Future studies designed to further explore and integrate the epigenetic mechanisms with lifestyle modification may lead to interdisciplinary interventions and novel preventive options for mitochondrial alteration and metabolic disorders. PMID:24552811

Cheng, Zhiyong; Almeida, Fabio A

2014-01-01

241

Aerobic training suppresses exercise-induced lipid peroxidation and inflammation in overweight/obese adolescent girls.  

PubMed

This study aimed to determine whether aerobic training could reduce lipid peroxidation and inflammation at rest and after maximal exhaustive exercise in overweight/obese adolescent girls. Thirty-nine adolescent girls (14-19 years old) were classified as nonobese or overweight/obese and then randomly assigned to either the nontrained or trained group (12-week multivariate aerobic training program). Measurements at the beginning of the experiment and at 3 months consisted of body composition, aerobic fitness (VO2peak) and the following blood assays: pre- and postexercise lipid peroxidation (15F2a-isoprostanes [F2-Isop], lipid hydroperoxide [ROOH], oxidized LDL [ox-LDL]) and inflammation (myeloperoxidase [MPO]) markers. In the overweight/ obese group, the training program significantly increased their fat-free mass (FFM) and decreased their percentage of fat mass (%FM) and hip circumference but did not modify their VO2peak. Conversely, in the nontrained overweight/obese group, weight and %FM increased, and VO2peak decreased, during the same period. Training also prevented exercise-induced lipid peroxidation and/or inflammation in overweight/obese girls (F2-Isop, ROOH, ox-LDL, MPO). In addition, in the trained overweight/obese group, exercise-induced changes in ROOH, ox-LDL and F2-Isop were correlated with improvements in anthropometric parameters (waist-to-hip ratio, %FM and FFM). In conclusion aerobic training increased tolerance to exercise-induced oxidative stress in overweight/obese adolescent girls partly as a result of improved body composition. PMID:25387489

Groussard, Carole; Youssef, Hala; Lemoine-Morel, Sophie; Pincemail, Joel; Jacob, Christophe; Moussa, Elie; Fazah, Abdallah; Cillard, Josiane; Pineau, Jean-Claude; Delamarche, Arlette

2015-02-01

242

Loss of functional endothelial connexin40 results in exercise-induced hypertension in mice.  

PubMed

During activity, coordinated vasodilation of microcirculatory networks with upstream supply vessels increases blood flow to skeletal and cardiac muscles and reduces peripheral resistance. Endothelial dysfunction in humans attenuates activity-dependent vasodilation, resulting in exercise-induced hypertension in otherwise normotensive individuals. Underpinning activity-dependent hyperemia is an ascending vasodilation in which the endothelial gap junction protein, connexin (Cx)40, plays an essential role. Because exercise-induced hypertension is proposed as a forerunner to clinical hypertension, we hypothesized that endothelial disruption of Cx40 function in mice may create an animal model of this condition. To this end, we created mice in which a mutant Cx40T152A was expressed alongside wildtype Cx40 selectively in the endothelium. Expression of the Cx40T152A transgene in Xenopus oocytes and mouse coronary endothelial cells in vitro impaired both electric and chemical conductance and acted as a dominant-negative against wildtype Cx40, Cx43, and Cx45, but not Cx37. Endothelial expression of Cx40T152A in Cx40T152ATg mice attenuated ascending vasodilation, without effect on radial coupling through myoendothelial gap junctions. Using radiotelemetry, Cx40T152ATg mice showed an activity-dependent increase in blood pressure, which was significantly greater than in wildtype mice, but significantly less than in chronically hypertensive, Cx40knockout mice. The increase in heart rate with activity was also greater than in wildtype or Cx40knockout mice. We conclude that the endothelial Cx40T152A mutation attenuates activity-dependent vasodilation, producing a model of exercise-induced hypertension. These data highlight the importance of endothelial coupling through Cx40 in regulating blood pressure during activity. PMID:25547341

Morton, Susan K; Chaston, Daniel J; Howitt, Lauren; Heisler, Jillian; Nicholson, Bruce J; Fairweather, Stephen; Bröer, Stefan; Ashton, Anthony W; Matthaei, Klaus I; Hill, Caryl E

2015-03-01

243

Exercise-induced hemostatic alterations are detectable by rotation thrombelastography (ROTEM): A marathon study.  

PubMed

Rotation thrombelastography (ROTEM) provides a whole blood assay that allows the assessment of plasmic- and platelet-related hemostasis in a single-step procedure. In our current study, we focused on the capability of the method to detect hemostatic alterations induced by physical exercise, enrolling 33 healthy participants of the Dusseldorf Marathon 2006. Venous blood drawn immediately before and after finishing the marathon was analyzed by a rotational thrombelastograph (Pentapharm, Munich, Germany). On initiation of blood coagulation by recalcification, standard ROTEM parameters were determined. Comparison of the results obtained before and after the physical exercise was performed using the Student t test for paired samples. As a result, the mean clotting time (CT) determined from blood samples obtained immediately after the marathon was significantly shorter (662.9 + or - 67.8 seconds vs 505.6 + or - 97.3 seconds, P = .002) and the mean maximal clot firmness was significantly broader (48.4 +/- 6.6 mm vs 51.5 +/- 4.5 mm, P = .0004) when compared to results obtained before the physical exercise. Differences between mean clot formation times (CFTs; 280.6 + 96 seconds vs 270.4 + or - 73.8 seconds) and mean alpha angles (45.9 degrees + or - 8 degrees vs 47.8 degrees + or - 5.8 degrees ) before and after the marathon were not statistically significant. Remarkably, some participants showed opposed results, particularly prolongation of CT and narrowing of maximum clot firmness (MCF). Our study demonstrates that ROTEM is sensitive to exercise-induced hemostatic alterations. The method appears to be capable of detecting even distinct changes in hemostasis in a single-step procedure. Further analyses are needed to clarify which hemostasis parameters influence ROTEM results and which ROTEM results are independent predictors of exercise-induced alterations of plasmic and platelet function. This might help to explain interindividual differences in exercise-induced alterations of hemostasis. PMID:19696040

Sucker, Christoph; Zotz, Rainer B; Senft, Beate; Scharf, Rudiger E; Kröger, Knut; Erbel, Raimund; Möhlenkamp, Stefan

2010-10-01

244

Acute Calcium Ingestion Attenuates Exercise-induced Disruption of Calcium Homeostasis  

PubMed Central

Purpose Exercise is associated with a decrease in bone mineral density under certain conditions. One potential mechanism is increased bone resorption due to an exercise-induced increase in parathyroid hormone (PTH), possibly triggered by dermal calcium loss. The purpose of this investigation was to determine whether calcium supplementation either before or during exercise attenuates exercise-induced increases in PTH and C-terminal telopeptide of type I collagen (CTX; a marker of bone resorption). Methods Male endurance athletes (n=20) completed three 35-km cycling time trials under differing calcium supplementation conditions: 1) 1000 mg calcium 20 minutes before exercise and placebo during, 2) placebo before and 250 mg calcium every 15 minutes during exercise (1000 mg total), or 3) placebo before and during exercise. Calcium was delivered in a 1000 mg/L solution. Supplementation was double-blinded and trials were performed in random order. PTH, CTX, bone-specific alkaline phosphatase (BAP; a marker of bone formation), and ionized calcium (iCa) were measured before and immediately after exercise. Results CTX increased and iCa decreased similarly in response to exercise under all test conditions. When compared to placebo, calcium supplementation before exercise attenuated the increase in PTH (55.8 ± 15.0 vs. 74.0 ± 14.2; mean ± SE; p=0.04); there was a similar trend (58.0 ± 17.4; p=0.07) for calcium supplementation during exercise. There were no effects of calcium on changes in CTX, BAP, and iCa. Conclusions Calcium supplementation before exercise attenuated the disruption of PTH. Further research is needed to determine the effects of repeated increases in PTH and CTX on bone (i.e., exercise training), and whether calcium supplementation can diminish any exercise-induced demineralization. PMID:20798655

Barry, Daniel W; Hansen, Kent C; Van Pelt, Rachael E; Witten, Michael; Wolfe, Pamela; Kohrt, Wendy M

2011-01-01

245

Genetic influences on exercise-induced adult hippocampal neurogenesis across 12 divergent mouse strains  

PubMed Central

New neurons are continuously born in the hippocampus of several mammalian species throughout adulthood. Adult neurogenesis represents a natural model for understanding how to grow and incorporate new nerve cells into pre-existing circuits in the brain. Finding molecules or biological pathways that increase neurogenesis has broad potential for regenerative medicine. One strategy is to identify mouse strains that display large versus small increases in neurogenesis in response to wheel running so the strains can be contrasted to find common genes or biological pathways associated with enhanced neuron formation. Therefore, mice from 12 different isogenic strains were housed with or without running wheels for 43 days to measure the genetic regulation of exercise-induced neurogenesis. The first 10 days mice received daily injections of BrdU to label dividing cells. Neurogenesis was measured as the total number of BrdU cells co-expressing NeuN mature neuronal marker in the hippocampal granule cell layer by immunohistochemistry. Exercise increased neurogenesis in all strains, but the magnitude significantly depended on genotype. Strain means for distance run on wheels, but not distance traveled in cages without wheels, were significantly correlated with strain mean level of neurogenesis. Further, certain strains displayed greater neurogenesis than others for a fixed level of running. Strain means for neurogenesis under sedentary conditions were not correlated with neurogenesis under runner conditions suggesting that different genes influence baseline versus exercise-induced neurogenesis. Genetic contributions to exercise-induced hippocampal neurogenesis suggest that it may be possible to identify genes and pathways associated with enhanced neuroplastic responses to exercise. PMID:21223504

Clark, Peter J.; Kohman, Rachel A.; Miller, Daniel S.; Bhattacharya, Tushar K.; Brzezinska, Weronika J.; Rhodes, Justin S.

2011-01-01

246

The influence of ice slushy on voluntary contraction force following exercise-induced hyperthermia.  

PubMed

This study aimed to investigate the effect of exercise-induced hyperthermia on central fatigue and force decline in exercised and nonexercised muscles and whether ingestion of ice slushy (ICE) ameliorates fatigue. Eight participants (5 males, 3 females) completed 45 s maximal voluntary isometric contractions (MVIC) with elbow flexors and knee extensors at baseline and following an exercise-induced rectal temperature (Trec) of 39.3 ± 0.2 °C. Percutaneous electrical muscle stimulation was superimposed at 15, 30 and 44 s during MVICs to assess muscle activation. To increase Trec to 39.3 °C, participants cycled at 60% maximum power output for 42 ± 11 min in 40 °C and 50% relative humidity. Immediately prior to each MVIC, participants consumed 50 g of ICE (-1 °C) or thermoneutral drink (38 °C, CON) made from 7.4% carbohydrate beverage. Participants consumed water (19 °C) during exercise to prevent hypohydration. Voluntary muscle force production and activation in both muscle groups were unchanged at Trec 39.3 °C with ICE (knee extensors: 209 ± 152 N) versus CON (knee extensors: 255 ± 157 N, p = 0.19). At Trec 39.3 °C, quadriceps mean force (232 ± 151 N) decreased versus baseline (302 ± 180 N, p < 0.001) and mean voluntary activation was also decreased (by 15% ± 11%, p < 0.001). Elbow flexor mean force decreased from 179 ± 67 N to 148 ± 65 N when Trec was increased to 39.3 °C (p < 0.001) but mean voluntary activation was not reduced at 39.3 °C (5% ± 25%, p = 0.79). After exercise-induced hyperthermia, ICE had no effect on voluntary activation or force production; however, both were reduced from baseline in the exercised muscle group. Peripheral fatigue was greater than the central component and limited the ability of an intervention designed to alter central fatigue. PMID:24971678

Burdon, Catriona A; Easthope, Christopher S; Johnson, Nathan A; Chapman, Phillip G; O'Connor, Helen

2014-07-01

247

Peroxisome biogenesis in mammalian cells  

PubMed Central

To investigate peroxisome assembly and human peroxisome biogenesis disorders (PBDs) such as Zellweger syndrome, thirteen different complementation groups (CGs) of Chinese hamster ovary (CHO) cell mutants defective in peroxisome biogenesis have been isolated and established as a model research system. Successful gene-cloning studies by a forward genetic approach utilized a rapid functional complementation assay of CHO cell mutants led to isolation of human peroxin (PEX) genes. Search for pathogenic genes responsible for PBDs of all 14 CGs is now completed together with the homology search by screening the human expressed sequence tag database using yeast PEX genes. Peroxins are divided into three groups: (1) peroxins including Pex3p, Pex16p, and Pex19p, are responsible for peroxisome membrane biogenesis via classes I and II pathways; (2) peroxins that function in matrix protein import; (3) those such as three forms of Pex11p, Pex11p?, Pex11p?, and Pex11p?, are involved in peroxisome proliferation where DLP1, Mff, and Fis1 coordinately function. In membrane assembly, Pex19p forms complexes in the cytosol with newly synthesized PMPs including Pex16p and transports them to the receptor Pex3p, whereby peroxisomal membrane is formed (Class I pathway). Pex19p likewise forms a complex with newly made Pex3p and translocates it to the Pex3p receptor, Pex16p (Class II pathway). In matrix protein import, newly synthesized proteins harboring peroxisome targeting signal type 1 or 2 are recognized by Pex5p or Pex7p in the cytoplasm and are imported to peroxisomes via translocation machinery. In regard to peroxisome-cytoplasmic shuttling of Pex5p, Pex5p initially targets to an 800-kDa docking complex consisting of Pex14p and Pex13p and then translocates to a 500-kDa RING translocation complex. At the terminal step, Pex1p and Pex6p of the AAA family mediate the export of Pex5p, where Cys-ubiquitination of Pex5p is essential for the Pex5p exit. PMID:25177298

Fujiki, Yukio; Okumoto, Kanji; Mukai, Satoru; Honsho, Masanori; Tamura, Shigehiko

2014-01-01

248

Valsartan regulates myocardial autophagy and mitochondrial turnover in experimental hypertension.  

PubMed

Renovascular hypertension alters cardiac structure and function. Autophagy is activated during left ventricular hypertrophy and linked to adverse cardiac function. The angiotensin II receptor blocker, valsartan, lowers blood pressure and is cardioprotective, but whether it modulates autophagy in the myocardium is unclear. We hypothesized that valsartan would alleviate autophagy and improve left ventricular myocardial mitochondrial turnover in swine renovascular hypertension. Domestic pigs were randomized to control, unilateral renovascular hypertension, and renovascular hypertension treated with valsartan (320 mg/d) or conventional triple therapy (reserpine+hydralazine+hydrochlorothiazide) for 4 weeks after 6 weeks of renovascular hypertension (n=7 each group). Left ventricular remodeling, function, and myocardial oxygenation and microcirculation were assessed by multidetector computer tomography, blood oxygen level-dependent MRI, and microcomputer tomography. Myocardial autophagy, markers for mitochondrial degradation and biogenesis, and mitochondrial respiratory-chain proteins were examined ex vivo. Renovascular hypertension induced left ventricular hypertrophy and myocardial hypoxia, enhanced cellular autophagy and mitochondrial degradation, and suppressed mitochondrial biogenesis. Valsartan and triple therapy similarly decreased blood pressure, but valsartan solely alleviated left ventricular hypertrophy, ameliorated myocardial autophagy and mitophagy, and increased mitochondrial biogenesis. In contrast, triple therapy only slightly attenuated autophagy and preserved mitochondrial proteins, but elicited no improvement in mitophagy. These data suggest a novel potential role of valsartan in modulating myocardial autophagy and mitochondrial turnover in renovascular hypertension-induced hypertensive heart disease, which may possibly bolster cardiac repair via a blood pressure-independent manner. PMID:24752430

Zhang, Xin; Li, Zi-Lun; Crane, John A; Jordan, Kyra L; Pawar, Aditya S; Textor, Stephen C; Lerman, Amir; Lerman, Lilach O

2014-07-01

249

Effects of eccentric exercise-induced muscle damage on intramyocellular lipid concentration and high energy phosphates  

Microsoft Academic Search

Eccentric exercise is known to cause changes to the ultrastructure of skeletal muscle and, in turn, may alter the ability\\u000a of the muscle to store and utilise intracellular substrates such as intramyocellular lipid (IMCL). The purpose of this study\\u000a was to test the hypothesis that exercise-induced muscle damage (EIMD) results in IMCL accumulation. Six males (31 ± 6 years;\\u000a mean ± SD, and 72.3 ± 9.7 kg body

Jonathan D. Hughes; Nathan A. Johnson; Stephen J. Brown; Toos Sachinwalla; David W. Walton; Stephen R. Stannard

2010-01-01

250

Food-dependent exercise-induced anaphylaxis with negative allergy testing.  

PubMed

Food-dependent exercise-induced anaphylaxis (FDEIA) is a disorder where exercise following allergen ingestion triggers anaphylaxis although exercise and allergen exposure are independently tolerated. The diagnosis of FDEIA is based on a characteristic clinical history. The culprit allergen is usually confirmed through the use of skin prick testing (SPT) serum-specific IgE levels and a food-exercise challenge. We present a case of FDEIA suggested by clinical history and open food-exercise challenge with negative specific IgE levels and SPT that highlights the challenges involved in diagnosing and managing this rare disorder. PMID:24503659

Kleiman, Jacob; Ben-Shoshan, Moshe

2014-01-01

251

The influence of ice slurry ingestion on maximal voluntary contraction following exercise-induced hyperthermia  

Microsoft Academic Search

The purpose of this study was to determine whether ingestion of a small bolus of ice slurry (1.25 g kg?1) could attenuate the reduction in maximal voluntary isometric contraction (MVC) torque output during a 2-min sustained task\\u000a following exercise-induced hyperthermia. On two separate occasions, 10 males (age: 24 ± 3 years, $$ \\\\dot{V}{\\\\text{O}}_{{ 2 {\\\\text{peak}}}} $$: 49.8 ± 4.7 ml kg?1 min?1) ran to exhaustion at their first ventilatory threshold

Rodney SiegelJoseph; Joseph Maté; Greig Watson; Kazunori Nosaka; Paul B. Laursen

252

Two cases of food-dependent exercise-induced anaphylaxis with different culprit foods  

PubMed Central

Food-dependent exercise-induced anaphylaxis (FDEIA) is one of the severe allergic reactions in which symptoms develop only if exercise takes place within a few hours of eating a specific food. It is important to consider FDEIA in cases of unexplained anaphylaxis as reactions can occur several hours after ingesting the culprit food(s). We herein report the first two cases of FDEIA in the Middle East. The first one is induced by wheat, while the other by peanut. The pathophysiology, predisposing factors, diagnosis, and treatment of FDEIA are also summarized here. PMID:24551018

Mobayed, Hassan M.S.; Ali Al-Nesf, Maryam

2014-01-01

253

High protein diet maintains glucose production during exercise-induced energy deficit: a controlled trial  

Microsoft Academic Search

Background  Inadequate energy intake induces changes in endogenous glucose production (GP) to preserve muscle mass. Whether addition provision\\u000a of dietary protein modulates GP response to energy deficit is unclear. The objective was to determine whether exercise-induced\\u000a energy deficit effects on glucose metabolism are mitigated by increased dietary protein.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Nineteen men ([mean ± SD] 23 ± 2 y, VO2peak 59 ± 5

Tracey J Smith; Jean-Marc Schwarz; Scott J Montain; Jennifer Rood; Matthew A Pikosky; Carmen Castaneda-Sceppa; Ellen Glickman; Andrew J Young

2011-01-01

254

Exercise-induced prostacyclin release positively correlates with VO(2max) in young healthy men.  

PubMed

In this study we have evaluated the effect of maximal incremental cycling exercise (IE) on the systemic release of prostacyclin (PGI(2)), assessed as plasma 6-keto-PGF(1alpha) concentration in young healthy men. Eleven physically active - untrained men (mean +/- S.D.) aged 22.7 +/- 2.1 years; body mass 76.3 +/- 9.1 kg; BMI 23.30 +/- 2.18 kg . m(-2); maximal oxygen uptake (VO(2max)) 46.5 +/- 3.9 ml . kg(-1) . min(-1), performed an IE test until exhaustion. Plasma concentrations of 6-keto-PGF(1alpha), lactate, and cytokines were measured in venous blood samples taken prior to the exercise and at the exhaustion. The net exercise-induced increase in 6-keto-PGF(1alpha) concentration, expressed as the difference between the end-exercise minus pre-exercise concentration positively correlated with VO(2max) (r=0.78, p=0.004) as well as with the net VO(2) increase at exhaustion (r=0.81, p=0.003), but not with other respiratory, cardiac, metabolic or inflammatory parameters of the exercise (minute ventilation, heart rate, plasma lactate, IL-6 or TNF-alpha concentrations). The exercise-induced increase in 6-keto-PGF(1alpha) concentration?? was significantly higher (p=0.008) in a group of subjects (n=5) with the highest VO(2max) when compared to the group of subjects with the lowest VO(2max), in which no increase in 6-keto-PGF(1alpha) concentration was found. In conclusion, we demonstrated, to our knowledge for the first time, that exercise-induced release of PGI(2) in young healthy men correlates with VO(2max), suggesting that vascular capacity to release PGI(2) in response to physical exercise represents an important factor characterizing exercise tolerance. Moreover, we postulate that the impairment of exercise-induced release of PGI(2) leads to the increased cardiovascular hazard of vigorous exercise. PMID:18380542

Zoladz, J A; Majerczak, J; Duda, K; Ch?opicki, S

2009-01-01

255

Plant Peroxisomes: Biogenesis and Function  

PubMed Central

Peroxisomes are eukaryotic organelles that are highly dynamic both in morphology and metabolism. Plant peroxisomes are involved in numerous processes, including primary and secondary metabolism, development, and responses to abiotic and biotic stresses. Considerable progress has been made in the identification of factors involved in peroxisomal biogenesis, revealing mechanisms that are both shared with and diverged from non-plant systems. Furthermore, recent advances have begun to reveal an unexpectedly large plant peroxisomal proteome and have increased our understanding of metabolic pathways in peroxisomes. Coordination of the biosynthesis, import, biochemical activity, and degradation of peroxisomal proteins allows for highly dynamic responses of peroxisomal metabolism to meet the needs of a plant. Knowledge gained from plant peroxisomal research will be instrumental to fully understanding the organelle’s dynamic behavior and defining peroxisomal metabolic networks, thus allowing the development of molecular strategies for rational engineering of plant metabolism, biomass production, stress tolerance, and pathogen defense. PMID:22669882

Hu, Jianping; Baker, Alison; Bartel, Bonnie; Linka, Nicole; Mullen, Robert T.; Reumann, Sigrun; Zolman, Bethany K.

2012-01-01

256

Strigol: biogenesis and physiological activity.  

PubMed

The role played by molecules of the strigolactone family in stimulating the germination of seeds of parasitic weeds of the genera Striga, Orobanche and Alectra has never been clearly elucidated. The biogenesis of these unusual terpenoid lactones, originally identified in minute quantities in the root exudates of a small number of host plants and two or three "false hosts", also remains obscure. These lactones, as the chemical signals which initiate the life cycle of Striga, are consequently at the forefront of the Striga research effort. This paper reviews recent key discoveries relating to the biosynthesis and mode of action of strigolactones, and summarises the evidence suggesting that these molecules may be far more widely distributed and have a greater physiological significance than has hitherto been appreciated. PMID:16483620

Humphrey, Andrew J; Beale, Michael H

2006-04-01

257

Evidence for Mitochondrial Respiratory Deficiency in Rat Rhabdomyosarcoma Cells  

PubMed Central

Background Mitochondria can sense signals linked to variations in energy demand to regulate nuclear gene expression. This retrograde signaling pathway is presumed to be involved in the regulation of myoblast proliferation and differentiation. Rhabdomyosarcoma cells are characterized by their failure to both irreversibly exit the cell cycle and complete myogenic differentiation. However, it is currently unknown whether mitochondria are involved in the failure of rhabdomyosarcoma cells to differentiate. Methodology/Principal Findings Mitochondrial biogenesis and metabolism were studied in rat L6E9 myoblasts and R1H rhabdomyosacoma cells during the cell cycle and after 36 hours of differentiation. Using a combination of flow cytometry, polarographic and molecular analyses, we evidenced a marked decrease in the cardiolipin content of R1H cells cultured in growth and differentiation media, together with a significant increase in the content of mitochondrial biogenesis factors and mitochondrial respiratory chain proteins. Altogether, these data indicate that the mitochondrial inner membrane composition and the overall process of mitochondrial biogenesis are markedly altered in R1H cells. Importantly, the dysregulation of protein-to-cardiolipin ratio was associated with major deficiencies in both basal and maximal mitochondrial respiration rates. This deficiency in mitochondrial respiration probably contributes to the inability of R1H cells to decrease mitochondrial H2O2 level at the onset of differentiation. Conclusion/Significance A defect in the regulation of mitochondrial biogenesis and mitochondrial metabolism may thus be an epigenetic mechanism that may contribute to the tumoral behavior of R1H cells. Our data underline the importance of mitochondria in the regulation of myogenic differentiation. PMID:20072609

Jahnke, Vanessa E.; Sabido, Odile; Defour, Aurélia; Castells, Josiane; Lefai, Etienne; Roussel, Damien; Freyssenet, Damien

2010-01-01

258

Mitochondrial biogenesis and angiogenesis in skeletal muscle of the elderly.  

PubMed

The aim of this study was to test the hypotheses that 1) skeletal muscles of elderly subjects can adapt to a single endurance exercise bout and 2) endurance trained elderly subjects have higher expression/activity of oxidative and angiogenic proteins in skeletal muscle than untrained elderly people. To investigate this, lifelong endurance trained elderly (ET; n = 8) aged 71.3 ± 3.4 years and untrained elderly subjects (UT; n = 7) aged 71.3 ± 4 years, performed a cycling exercise bout at 75% VO(2max) with vastus lateralis muscle biopsies obtained before (Pre), immediately after exercise (0 h) and at 2 h of recovery. Capillarization was detected histochemically and oxidative enzyme activities were determined on isolated mitochondria. GLUT4, HKII, Cyt c and VEGF protein expression was measured on muscle lysates from Pre-biopsies, phosphorylation of AMPK and P38 on lysates from Pre and 0 h biopsies, while PGC-1?, VEGF, HKII and TFAM mRNA content was determined at all time points. ET had ~40% higher PDH, CS, SDH, ?-KG-DH and ATP synthase activities and 27% higher capillarization than UT, reflecting increased skeletal muscle oxidative capacity with lifelong endurance exercise training. In addition, acute exercise increased in UT PGC-1? mRNA 11-fold and VEGF mRNA 4-fold at 2 h of recovery, and AMPK phosphorylation ~5-fold immediately after exercise, relative to Pre, indicating an ability to adapt metabolically and angiogenically to endurance exercise. However, in ET PGC-1? mRNA only increased 5 fold and AMPK phosphorylation ~2-fold, while VEGF mRNA remained unchanged after the acute exercise bout. P38 increased similarly in ET and UT after exercise. In conclusion, the present findings suggest that lifelong endurance exercise training ensures an improved oxidative capacity of skeletal muscle, and that skeletal muscle of elderly subjects maintains the ability to respond to acute endurance exercise. PMID:21504786

Iversen, Ninna; Krustrup, Peter; Rasmussen, Hans N; Rasmussen, Ulla F; Saltin, Bengt; Pilegaard, Henriette

2011-08-01

259

Unravelling mitochondrial pathways to Parkinson's disease.  

PubMed

Mitochondria are essential for cellular function due to their role in ATP production, calcium homeostasis and apoptotic signalling. Neurons are heavily reliant on mitochondrial integrity for their complex signalling, plasticity and excitability properties, and to ensure cell survival over decades. The maintenance of a pool of healthy mitochondria that can meet the bioenergetic demands of a neuron, is therefore of critical importance; this is achieved by maintaining a careful balance between mitochondrial biogenesis, mitochondrial trafficking, mitochondrial dynamics and mitophagy. The molecular mechanisms that underlie these processes are gradually being elucidated. It is widely recognized that mitochondrial dysfunction occurs in many neurodegenerative diseases, including Parkinson's disease. Mitochondrial dysfunction in the form of reduced bioenergetic capacity, increased oxidative stress and reduced resistance to stress, is observed in several Parkinson's disease models. However, identification of the recessive genes implicated in Parkinson's disease has revealed a common pathway involving mitochondrial dynamics, transport, turnover and mitophagy. This body of work has led to the hypothesis that the homeostatic mechanisms that ensure a healthy mitochondrial pool are key to neuronal function and integrity. In this paradigm, impaired mitochondrial dynamics and clearance result in the accumulation of damaged and dysfunctional mitochondria, which may directly induce neuronal dysfunction and death. In this review, we consider the mechanisms by which mitochondrial dysfunction may lead to neurodegeneration. In particular, we focus on the mechanisms that underlie mitochondrial homeostasis, and discuss their importance in neuronal integrity and neurodegeneration in Parkinson's disease. PMID:24117181

Celardo, I; Martins, L M; Gandhi, S

2014-04-01

260

Exercise improves mitochondrial and redox-regulated stress responses in the elderly: better late than never!  

PubMed

Ageing is associated with several physiological declines to both the cardiovascular (e.g. reduced aerobic capacity) and musculoskeletal system (muscle function and mass). Ageing may also impair the adaptive response of skeletal muscle mitochondria and redox-regulated stress responses to an acute exercise bout, at least in mice and rodents. This is a functionally important phenomenon, since (1) aberrant mitochondrial and redox homeostasis are implicated in the pathophysiology of musculoskeletal ageing and (2) the response to repeated exercise bouts promotes exercise adaptations and some of these adaptations (e.g. improved aerobic capacity and exercise-induced mitochondrial remodelling) offset age-related physiological decline. Exercise-induced mitochondrial remodelling is mediated by upstream signalling events that converge on downstream transcriptional co-factors and factors that orchestrate a co-ordinated nuclear and mitochondrial transcriptional response associated with mitochondrial remodelling. Recent translational human investigations have demonstrated similar exercise-induced mitochondrial signalling responses in older compared with younger skeletal muscle, regardless of training status. This is consistent with data indicating normative mitochondrial remodelling responses to long-term exercise training in the elderly. Thus, human ageing is not accompanied by diminished mitochondrial plasticity to acute and chronic exercise stimuli, at least for the signalling pathways measured to date. Exercise-induced increases in reactive oxygen and nitrogen species promote an acute redox-regulated stress response that manifests as increased heat shock protein and antioxidant enzyme content. In accordance with previous reports in rodents and mice, it appears that sedentary ageing is associated with a severely attenuated exercise-induced redox stress response that might be related to an absent redox signal. In this regard, regular exercise training affords some protection but does not completely override age-related defects. Despite some failed redox-regulated stress responses, it seems mitochondrial responses to exercise training are intact in skeletal muscle with age and this might underpin the protective effect of exercise training on age-related musculoskeletal decline. Whilst further investigation is required, recent data suggest that it is never too late to begin exercise training and that lifelong training provides protection against several age-related declines at both the molecular (e.g. reduced mitochondrial function) and whole-body level (e.g. aerobic capacity). PMID:25537184

Cobley, James N; Moult, Peter R; Burniston, Jatin G; Morton, James P; Close, Graeme L

2015-04-01

261

Exercise-induced silent myocardial ischemia: Evaluation by thallium-201 emission computed tomography  

SciTech Connect

Factors associated with silent myocardial ischemia (SMI) during exercise testing were studied by means of thallium-201 emission computed tomography (ECT) in 471 patients. Coronary angiography was done in 290, of whom 167 were found to have significant coronary artery disease (CAD). Exercise-induced ischemia and its severity were defined with ECT. During exercise 108 (62%) of 173 patients with ischemia and 57 (50%) of 115 with ischemia and angiographically documented CAD had no chest pain. One third of the patients showed an inconsistency between scintigraphic ischemia and ischemia ST depression. Age, sex, prior myocardial infarction, and diabetes mellitus were not related to SMI. Patients with SMI had less severe ischemia despite a higher peak double product compared to those with painful ischemia. Among 91 with prior myocardial infarction and exercise-induced ischemia, 51 with periinfarction ischemia had a higher frequency of SMI than did 14 with ischemia remote from the prior infarct zone despite similarities in the severity of ischemia. In conclusion, factors localized within ischemic myocardium such as less severe ischemia or adjacency to a prior infarct made SMI more prevalent.

Kurata, C.; Sakata, K.; Taguchi, T.; Kobayashi, A.; Yamazaki, N. (Hamamatsu Univ. School of Medicine (Japan))

1990-03-01

262

The endocannabinoid system mediates aerobic exercise-induced antinociception in rats.  

PubMed

Exercise-induced antinociception is widely described in the literature, but the mechanisms involved in this phenomenon are poorly understood. Systemic (s.c.) and central (i.t., i.c.v.) pretreatment with CB? and CB? cannabinoid receptor antagonists (AM251 and AM630) blocked the antinociception induced by an aerobic exercise (AE) protocol in both mechanical and thermal nociceptive tests. Western blot analysis revealed an increase and activation of CB? receptors in the rat brain, and immunofluorescence analysis demonstrated an increase of activation and expression of CB? receptors in neurons of the periaqueductal gray matter (PAG) after exercise. Additionally, pretreatment (s.c., i.t. and i.c.v.) with endocannabinoid metabolizing enzyme inhibitors (MAFP and JZL184) and an anandamide reuptake inhibitor (VDM11) prolonged and intensified this antinociceptive effect. These results indicate that exercise could activate the endocannabinoid system, producing antinociception. Supporting this hypothesis, liquid-chromatography/mass-spectrometry measurements demonstrated that plasma levels of endocannabinoids (anandamide and 2-arachidonoylglycerol) and of anandamide-related mediators (palmitoylethanolamide and oleoylethanolamide) were increased after AE. Therefore, these results suggest that the endocannabinoid system mediates aerobic exercise-induced antinociception at peripheral and central levels. PMID:24148812

Galdino, Giovane; Romero, Thiago R L; Silva, José Felipe P; Aguiar, Daniele C; de Paula, Ana Maria; Cruz, Jader S; Parrella, Cosimo; Piscitelli, Fabiana; Duarte, Igor D; Di Marzo, Vincenzo; Perez, Andrea C

2014-02-01

263

Exercise-induced cardiac fatigue in low and normal birth weight young black adults.  

PubMed

The objective of the study was to compare the change in diastolic function, E/A ratio, in response to prolonged exercise in low birth weight and normal birth weight individuals. Using a case-control study design, 23 students of the University of Zimbabwe College of Health Sciences who had neonatal clinic cards as proof of birth weight were recruited into the study. Measurements of diastolic function, E/A ratio, were obtained using an echocardiogram before and after 75 minutes of exercise. Among the cohort, seven had low birth weight - <2500 g, three female patients and four male patients - and 16 had normal birth weight - six female patients and 10 male patients). The mean age was 20.7±3.3 years. After prolonged exercise for 75 minutes of running on a treadmill, decreases in diastolic function, E/A ratio, were significantly greater in low birth weight than in normal birth weight individuals (0.48±0.27 versus 0.19±0.18 p<0.05, respectively). There was a significant association between low birth weight and exercise-induced cardiac fatigue (the ?2 test p<0.05, odds ratio 4.64, 95% confidence interval 1.19-18.1). We conclude that low birth weight is associated with exercise-induced diastolic dysfunction in young adults. PMID:24713506

Chifamba, Jephat; Mapfumo, Chidochashe; Mawoneke, Dorcas W; Gwaunza, Lenon T; Allen, Larry A; Chinyanga, Herbert M

2015-03-01

264

Circulating adrenaline and noradrenaline concentrations during exercise in patients with exercise induced asthma and normal subjects.  

PubMed Central

A failure of the usual increase in plasma adrenaline and noradrenaline concentrations during submaximal exercise has been suggested as a contributory cause of exercise induced asthma. Six normal subjects and six asthmatic patients underwent a standard graded maximal exercise test. Measurements of oxygen consumption, minute ventilation, exercise time, blood lactate concentration, and heart rate indicated that the two groups achieved similarly high work loads during exercise. Mean FEV1 fell by 20% in asthmatic patients after exercise. Basal plasma adrenaline concentrations (nmol/l) increased in normal subjects from 0.05 to 2.7 and in asthmatic patients from 0.12 to 1.6 at peak exercise. Noradrenaline concentrations (nmol/l) increased in normal subjects from 2.0 to 14.3 and in asthmatic patients from 1.9 to 13.7 at peak exercise. The increases in adrenaline and noradrenaline in the asthmatic patients did not differ significantly from the increases in normal subjects. Thus a reduced sympathoadrenal response to exercise seems unlikely to be an important mechanism in the pathogenesis of exercise induced asthma. PMID:3406917

Berkin, K E; Walker, G; Inglis, G C; Ball, S G; Thomson, N C

1988-01-01

265

An in vivo correlate of exercise-induced neurogenesis in the adult dentate gyrus  

PubMed Central

With continued debate over the functional significance of adult neurogenesis, identifying an in vivo correlate of neurogenesis has become an important goal. Here we rely on the coupling between neurogenesis and angiogenesis and test whether MRI measurements of cerebral blood volume (CBV) provide an imaging correlate of neurogenesis. First, we used an MRI approach to generate CBV maps over time in the hippocampal formation of exercising mice. Among all hippocampal subregions, exercise was found to have a primary effect on dentate gyrus CBV, the only subregion that supports adult neurogenesis. Moreover, exercise-induced increases in dentate gyrus CBV were found to correlate with postmortem measurements of neurogenesis. Second, using similar MRI technologies, we generated CBV maps over time in the hippocampal formation of exercising humans. As in mice, exercise was found to have a primary effect on dentate gyrus CBV, and the CBV changes were found to selectively correlate with cardiopulmonary and cognitive function. Taken together, these findings show that dentate gyrus CBV provides an imaging correlate of exercise-induced neurogenesis and that exercise differentially targets the dentate gyrus, a hippocampal subregion important for memory and implicated in cognitive aging. PMID:17374720

Pereira, Ana C.; Huddleston, Dan E.; Brickman, Adam M.; Sosunov, Alexander A.; Hen, Rene; McKhann, Guy M.; Sloan, Richard; Gage, Fred H.; Brown, Truman R.; Small, Scott A.

2007-01-01

266

Duration of action of sodium cromoglycate on exercise induced asthma: comparison of 2 formulations.  

PubMed

Thirteen asthmatic children aged 9-14 years participated in a double blind randomised trial to compare the effectiveness and duration of action of 2 formulations of sodium cromoglycate; one a 20 mg capsule of powdered sodium cromoglycate delivered by turbo inhaler (spinhaler), and the other 1 mg of aerosolised sodium cromoglycate delivered by pressurised cannister inhaler (aerosol). The children performed exercise tests on each of 3 days in a 10 day period--15 minutes, 2 hours, and 6 hours after inhalation of powder, aerosol, or a placebo. Two patients were not protected from exercise induced asthma by either formulation of sodium cromoglycate. Among the remaining patients both formulations gave good protection from exercise induced asthma 15 minutes after inhalation, and the effect of both wore off steadily over the next 6 hours. The spinhaler gave appreciably better protection than the aerosol at 15 minutes after inhalation, and was the only formulation to provide good protection at 2 hours and 6 hours. The more limited effectiveness of the aerosol may be explained by the lower dose of sodium cromoglycate and the more complicated inhalation technique required. PMID:6412638

Bar-Yishay, E; Gur, I; Levy, M; Volozni, D; Godfrey, S

1983-08-01

267

Tdrkh is essential for spermatogenesis and participates in primary piRNA biogenesis in the germline  

PubMed Central

Piwi proteins and Piwi-interacting RNAs (piRNAs) repress transposition, regulate translation, and guide epigenetic programming in the germline. Here, we show that an evolutionarily conserved Tudor and KH domain-containing protein, Tdrkh (a.k.a. Tdrd2), is required for spermatogenesis and involved in piRNA biogenesis. Tdrkh partners with Miwi and Miwi2 via symmetrically dimethylated arginine residues in Miwi and Miwi2. Tdrkh is a mitochondrial protein often juxtaposed to pi-bodies and piP-bodies and is required for Tdrd1 cytoplasmic localization and Miwi2 nuclear localization. Tdrkh mutants display meiotic arrest at the zygotene stage, attenuate methylation of Line1 DNA, and upregulate Line1 RNA and protein, without inducing apoptosis. Furthermore, Tdrkh mutants have severely reduced levels of mature piRNAs but accumulate a distinct population of 1?U-containing, 2?O-methylated 31–37?nt RNAs that largely complement the missing mature piRNAs. Our results demonstrate that the primary piRNA biogenesis pathway involves 3??5? processing of 31–37?nt intermediates and that Tdrkh promotes this final step of piRNA biogenesis but not the ping-pong cycle. These results shed light on mechanisms underlying primary piRNA biogenesis, an area in which information is conspicuously absent. PMID:23714778

Saxe, Jonathan P; Chen, Mengjie; Zhao, Hongyu; Lin, Haifan

2013-01-01

268

Two dimensional echocardiographic evaluation of exercise-induced left and right ventricular asynergy: correlation with thallium scanning  

SciTech Connect

Adequate real time two dimensional echocardiograms were prospectively obtained before and immediately after graded treadmill exercise testing in 41 of 48 patients who underwent cardiac catheterization for suspected coronary artery disease. Findings were correlated with thallium perfusion scans performed 5 to 10 minutes and 3 hours after the same exercise test. Exercise-induced wall motion abnormalities were detected in 19 of 23 patients with significant coronary artery disease and no prior myocardial infarction as well as in all 5 patients with known previous infarction. Three patients with coronary artery disease experienced new isolated right ventricular asynergy with exercise that would have been missed if only the left ventricle had been evaluated. Exercise-induced thallium perfusion defects showed good correlation with exercise-induced asynergy as detected with echocardiography. Two dimensional echocardiography performed immediately after treadmill stress testing is a feasible and rewarding technique in the evaluation of patients suspected to have coronary artery disease.

Maurer, G.; Nanda, N.C.

1981-10-01

269

Redox Regulation of Mitochondrial Function  

PubMed Central

Abstract Redox-dependent processes influence most cellular functions, such as differentiation, proliferation, and apoptosis. Mitochondria are at the center of these processes, as mitochondria both generate reactive oxygen species (ROS) that drive redox-sensitive events and respond to ROS-mediated changes in the cellular redox state. In this review, we examine the regulation of cellular ROS, their modes of production and removal, and the redox-sensitive targets that are modified by their flux. In particular, we focus on the actions of redox-sensitive targets that alter mitochondrial function and the role of these redox modifications on metabolism, mitochondrial biogenesis, receptor-mediated signaling, and apoptotic pathways. We also consider the role of mitochondria in modulating these pathways, and discuss how redox-dependent events may contribute to pathobiology by altering mitochondrial function. Antioxid. Redox Signal. 16, 1323–1367. PMID:22146081

Handy, Diane E.

2012-01-01

270

Redox regulation of mitochondrial fission, protein misfolding, synaptic damage, and neuronal cell death: potential implications for Alzheimer’s and Parkinson’s diseases  

Microsoft Academic Search

Normal mitochondrial dynamics consist of fission and fusion events giving rise to new mitochondria, a process termed mitochondrial\\u000a biogenesis. However, several neurodegenerative disorders manifest aberrant mitochondrial dynamics, resulting in morphological\\u000a abnormalities often associated with deficits in mitochondrial mobility and cell bioenergetics. Rarely, dysfunctional mitochondrial\\u000a occur in a familial pattern due to genetic mutations, but much more commonly patients manifest sporadic

Tomohiro Nakamura; Stuart A. Lipton

2010-01-01

271

PGC-1?, mitochondrial dysfunction, and Huntington's disease.  

PubMed

The constant high energy demand of neurons makes them rely heavily on their mitochondria. Dysfunction of mitochondrial energy metabolism leads to reduced ATP production, impaired calcium buffering, and generation of reactive oxygen species. There is strong evidence that mitochondrial dysfunction results in neurodegeneration and may contribute to the pathogenesis of Huntington's disease (HD). Studies over the past few years have implicated an impaired function of peroxisome proliferator-activated receptor (PPAR)-? coactivator-1? (PGC-1?), a transcriptional master coregulator of mitochondrial biogenesis, metabolism, and antioxidant defenses, in causing mitochondrial dysfunction in HD. Here we have attempted to discuss in a nutshell, the key findings on the role of PGC-1? in mitochondrial dysfunction in HD and its potential as a therapeutic target to cure HD. PMID:23602910

Johri, Ashu; Chandra, Abhishek; Beal, M Flint

2013-09-01

272

Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect in human  

E-print Network

1 Mitotane alters mitochondrial respiratory chain activity by inducing cytochrome c oxidase defect,p'-DDD) is the most effective medical therapy for adrenocortical carcinoma but its molecular mechanism of action, steroidogenesis, and mitochondrial respiratory chain, biogenesis and morphology, of mitotane exposure in two human

Paris-Sud XI, Université de

273

Distinct Pathways Mediate the Sorting of Tail-anchored Mitochondrial Outer Membrane Proteins  

Technology Transfer Automated Retrieval System (TEKTRAN)

Little is known about the biogenesis of tail-anchored (TA) proteins localized to the mitochondrial outer membrane in plant cells. To address this issue, we screened all of the (>500) known and predicted TA proteins in Arabidopsis for those annotated, based on Gene Ontology, to possess mitochondrial...

274

Mitochondrial donation Mitochondrial donation  

E-print Network

. Mitochondrial DNA does not affect the features that make each person unique, such as appearance and personality DNA disease, and multiple different organs can be affected as mitochondria are present in all tissues in 6500 children is thought to develop a serious mitochondrial disorder. There is no cure and our current

Newcastle upon Tyne, University of

275

The Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes  

PubMed Central

Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations. PMID:24639874

2014-01-01

276

Exercise induced hypercoagulability, increased von Willebrand factor and decreased thyroid hormone concentrations in sled dogs  

PubMed Central

Background Sled dogs performing endurance races have been reported to have a high incidence of gastric erosions or ulcerations and an increased risk of gastro intestinal bleeding leading to death in some cases. In addition, these dogs also become hypothyroid during training and exercise. Canine hypothyroidism has been shown to correlate with decreased von Willebrand factor antigen and potentially increased bleeding tendency. Whether increased gastro intestinal bleeding risk is exacerbated due to changes in the hemostatic balance is unknown. The aim of this study was to investigate the hemostatic balance in sled dogs before and after exercise and in addition evaluate any correlation to thyroid status. Twenty sled dogs have been assessed in untrained and trained condition and immediately after exercise. The first sample was collected in the autumn following a resting period, and subsequently the dogs were exposed to increased intensity of training. After four months the peak of physical condition was reached and a 68 km long sled pulling exercise was performed. Samples were collected before and immediately after the exercise. Evaluated parameters were: plasma thromboelastographic (TEG) R, SP, ? and MA, activated partial thromboplastin time (aPTT), prothrombin time (PT), fibrinogen, von Willebrand factor (vWf), D-dimer, platelet number, thyroid hormones, hematocrit and C-reactive protein (CRP). Results Exercise induced an overall hypercoagulable state characterized by significant decreases of TEG R and SP and an increase of ?, increased concentrations of plasma vWf and decreased aPTT. In addition, a proinflammatory status was seen by a significant increase of serum CRP concentrations. Thyroid status was confirmed to be hypothyroid as training and exercise induced significant decrease of thyroxin (T4), free thyroxin (fT4) and thyroxin stimulating hormone (TSH) concentrations. Fibrinogen decreased significantly and PT increased. The training-induced changes showed correlation between T4, fT4 and aPTT and correlation between TSH and fibrinogen. Exercise-induced changes showed correlation between T4 and PT. Conclusions Exercise was associated with a hypercoagulable state and an increase of vWf concentration in this group of sled dogs. Decreased thyroid hormone concentrations after training and exercise were confirmed, but were associated with increased and not decreased vWf in this group of sled dogs. PMID:24507241

2014-01-01

277

HDL biogenesis, remodeling, and catabolism.  

PubMed

In this chapter, we review how HDL is generated, remodeled, and catabolized in plasma. We describe key features of the proteins that participate in these processes, emphasizing how mutations in apolipoprotein A-I (apoA-I) and the other proteins affect HDL metabolism. The biogenesis of HDL initially requires functional interaction of apoA-I with the ATP-binding cassette transporter A1 (ABCA1) and subsequently interactions of the lipidated apoA-I forms with lecithin/cholesterol acyltransferase (LCAT). Mutations in these proteins either prevent or impair the formation and possibly the functionality of HDL. Remodeling and catabolism of HDL is the result of interactions of HDL with cell receptors and other membrane and plasma proteins including hepatic lipase (HL), endothelial lipase (EL), phospholipid transfer protein (PLTP), cholesteryl ester transfer protein (CETP), apolipoprotein M (apoM), scavenger receptor class B type I (SR-BI), ATP-binding cassette transporter G1 (ABCG1), the F1 subunit of ATPase (Ecto F1-ATPase), and the cubulin/megalin receptor. Similarly to apoA-I, apolipoprotein E and apolipoprotein A-IV were shown to form discrete HDL particles containing these apolipoproteins which may have important but still unexplored functions. Furthermore, several plasma proteins were found associated with HDL and may modulate its biological functions. The effect of these proteins on the functionality of HDL is the topic of ongoing research. PMID:25522986

Zannis, Vassilis I; Fotakis, Panagiotis; Koukos, Georgios; Kardassis, Dimitris; Ehnholm, Christian; Jauhiainen, Matti; Chroni, Angeliki

2015-01-01

278

Disruption of microRNA Biogenesis Confers Resistance to ER Stress-Induced Cell Death Upstream of the Mitochondrion  

PubMed Central

Global downregulation of microRNAs (miRNAs) is a common feature of human tumors and has been shown to enhance cancer progression. Several components of the miRNA biogenesis machinery (XPO5, DICER and TRBP) have been shown to act as haploinsufficient tumor suppressors. How the deregulation of miRNA biogenesis promotes tumor development is not clearly understood. Here we show that loss of miRNA biogenesis increased resistance to endoplasmic reticulum (ER) stress-induced cell death. We observed that HCT116 cells with a DICER hypomorphic mutation (Exn5/Exn5) or where DICER or DROSHA were knocked down were resistant to ER stress-induced cell death. Extensive analysis revealed little difference in the unfolded protein response (UPR) of WT compared to Exn5/Exn5 HCT116 cells upon ER stress treatment. However, analysis of the intrinsic apoptotic pathway showed that resistance occurred upstream of the mitochondria. In particular, BAX activation and dissipation of mitochondrial membrane potential was attenuated, and there was altered expression of BCL-2 family proteins. These observations demonstrate a key role for miRNAs as critical modulators of the ER stress response. In our model, downregulation of miRNA biogenesis delays ER stress-induced apoptosis. This suggests that disrupted miRNA biogenesis may contribute to cancer progression by inhibiting ER stress-induced cell death. PMID:23977393

Cawley, Karen; Logue, Susan E.; Gorman, Adrienne M.; Zeng, Qingping; Patterson, John; Gupta, Sanjeev; Samali, Afshin

2013-01-01

279

Exercise-induced pulmonary hemorrhage in a nonathlete: case report and review of physiology.  

PubMed

The integrity of the pulmonary blood-gas barrier is vulnerable to intense exercise in elite athletes, similar to the phenomenon of exercise-induced pulmonary hemorrhage in thoroughbred racehorses. A 50-year-old previously healthy man presented with acute onset shortness of breath, dry cough, and hypoxemia after engaging in an extremely vigorous game of handball. CT scan of the chest showed diffuse patchy air-space disease. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Infectious etiologies and bleeding diatheses were excluded by laboratory testing. Serological tests for ANCA-associated vasculitis, lupus, and Goodpasture's disease also were negative. A transthoracic echocardiogram was normal. The patient recovered completely on supportive therapy in less than 72 h. This case demonstrates strenuous exercise as a cause of diffuse alveolar hemorrhage in a previously healthy male with no apparent underlying cardiopulmonary disease. PMID:24532148

Diwakar, Amit; Schmidt, Gregory A

2014-04-01

280

Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice  

PubMed Central

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients develop cardiomyopathy, which significantly contributes to mortality. Antisense oligonucleotides (AOs) are a promising DMD therapy, restoring functional dystrophin protein by exon skipping. However, a major limitation with current AOs is the absence of dystrophin correction in heart. Pip peptide-AOs demonstrate high activity in cardiac muscle. To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin protein, which prevented the exercised induced progression of cardiomyopathy, normalising heart size as well as stabilising other cardiac parameters. Treated mice also exhibited significantly reduced cardiac fibrosis and improved sarcolemmal integrity. This work demonstrates that high levels of cardiac dystrophin restored by Pip peptide-AOs prevents further deterioration of cardiomyopathy and pathology following exercise in dystrophic DMD mice. PMID:25758104

Betts, Corinne A.; Saleh, Amer F.; Carr, Carolyn A.; Hammond, Suzan M.; Coenen-Stass, Anna M. L.; Godfrey, Caroline; McClorey, Graham; Varela, Miguel A.; Roberts, Thomas C.; Clarke, Kieran; Gait, Michael J.; Wood, Matthew J. A.

2015-01-01

281

Prevention of exercised induced cardiomyopathy following Pip-PMO treatment in dystrophic mdx mice.  

PubMed

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disorder caused by mutations in the Dmd gene. In addition to skeletal muscle wasting, DMD patients develop cardiomyopathy, which significantly contributes to mortality. Antisense oligonucleotides (AOs) are a promising DMD therapy, restoring functional dystrophin protein by exon skipping. However, a major limitation with current AOs is the absence of dystrophin correction in heart. Pip peptide-AOs demonstrate high activity in cardiac muscle. To determine their therapeutic value, dystrophic mdx mice were subject to forced exercise to model the DMD cardiac phenotype. Repeated peptide-AO treatments resulted in high levels of cardiac dystrophin protein, which prevented the exercised induced progression of cardiomyopathy, normalising heart size as well as stabilising other cardiac parameters. Treated mice also exhibited significantly reduced cardiac fibrosis and improved sarcolemmal integrity. This work demonstrates that high levels of cardiac dystrophin restored by Pip peptide-AOs prevents further deterioration of cardiomyopathy and pathology following exercise in dystrophic DMD mice. PMID:25758104

Betts, Corinne A; Saleh, Amer F; Carr, Carolyn A; Hammond, Suzan M; Coenen-Stass, Anna M L; Godfrey, Caroline; McClorey, Graham; Varela, Miguel A; Roberts, Thomas C; Clarke, Kieran; Gait, Michael J; Wood, Matthew J A

2015-01-01

282

Effects of oral glutamine supplementation on exercise-induced gastrointestinal permeability and tight junction protein expression  

PubMed Central

The objectives of this study are threefold: 1) to assess whether 7 days of oral glutamine (GLN) supplementation reduces exercise-induced intestinal permeability; 2) whether supplementation prevents the proinflammatory response; and 3) whether these changes are associated with upregulation of the heat shock response. On separate occasions, eight human subjects participated in baseline testing and in GLN and placebo (PLA) supplementation trials, followed by a 60-min treadmill run. Intestinal permeability was higher in the PLA trial compared with baseline and GLN trials (0.0604 ± 0.047 vs. 0.0218 ± 0.008 and 0.0272 ± 0.007, respectively; P < 0.05). I?B? expression in peripheral blood mononuclear cells was higher 240 min after exercise in the GLN trial compared with the PLA trial (1.411 ± 0.523 vs. 0.9839 ± 0.343, respectively; P < 0.05). In vitro using the intestinal epithelial cell line Caco-2, we measured effects of GLN supplementation (0, 4, and 6 mM) on heat-induced (37° or 41.8°C) heat shock protein 70 (HSP70), heat shock factor-1 (HSF-1), and occludin expression. HSF-1 and HSP70 levels increased in 6 mM supplementation at 41°C compared with 0 mM at 41°C (1.785 ± 0.495 vs. 0.6681 ± 0.290, and 1.973 ± 0.325 vs. 1.133 ± 0.129, respectively; P < 0.05). Occludin levels increased after 4 mM supplementation at 41°C and 6 mM at 41°C compared with 0 mM at 41°C (1.236 ± 0.219 and 1.849 ± 0.564 vs. 0.7434 ± 0.027, respectively; P < 0.001). GLN supplementation prevented exercise-induced permeability, possibly through HSF-1 activation. PMID:24285149

Lanphere, Kathryn R.; Kravitz, Len; Mermier, Christine M.; Schneider, Suzanne; Dokladny, Karol; Moseley, Pope L.

2013-01-01

283

Increased renal tubular sodium reabsorption during exercise-induced hypervolemia in humans  

NASA Technical Reports Server (NTRS)

We tested the hypothesis that renal tubular Na(+) reabsorption increased during the first 24 h of exercise-induced plasma volume expansion. Renal function was assessed 1 day after no-exercise control (C) or intermittent cycle ergometer exercise (Ex, 85% of peak O(2) uptake) for 2 h before and 3 h after saline loading (12.5 ml/kg over 30 min) in seven subjects. Ex reduced renal blood flow (p-aminohippurate clearance) compared with C (0.83 +/- 0.12 vs. 1.49 +/- 0.24 l/min, P < 0.05) but did not influence glomerular filtration rates (97 +/- 10 ml/min, inulin clearance). Fractional tubular reabsorption of Na(+) in the proximal tubules was higher in Ex than in C (P < 0.05). Saline loading decreased fractional tubular reabsorption of Na(+) from 99.1 +/- 0.1 to 98.7 +/- 0.1% (P < 0.05) in C but not in Ex (99.3 +/- 0.1 to 99.4 +/- 0.1%). Saline loading reduced plasma renin activity and plasma arginine vasopressin levels in C and Ex, although the magnitude of decrease was greater in C (P < 0.05). These results indicate that, during the acute phase of exercise-induced plasma volume expansion, increased tubular Na(+) reabsorption is directed primarily to the proximal tubules and is associated with a decrease in renal blood flow. In addition, saline infusion caused a smaller reduction in fluid-regulating hormones in Ex. The attenuated volume-regulatory response acts to preserve distal tubular Na(+) reabsorption during saline infusion 24 h after exercise.

Nagashima, K.; Wu, J.; Kavouras, S. A.; Mack, G. W.

2001-01-01

284

Acute Exercise-Induced Response of Monocyte Subtypes in Chronic Heart and Renal Failure  

PubMed Central

Purpose. Monocytes (Mon1-2-3) play a substantial role in low-grade inflammation associated with high cardiovascular morbidity and mortality of patients with chronic kidney disease (CKD) and chronic heart failure (CHF). The effect of an acute exercise bout on monocyte subsets in the setting of systemic inflammation is currently unknown. This study aims (1) to evaluate baseline distribution of monocyte subsets in CHF and CKD versus healthy subjects (HS) and (2) to evaluate the effect of an acute exercise bout. Exercise-induced IL-6 and MCP-1 release are related to the Mon1-2-3 response. Methods. Twenty CHF patients, 20 CKD patients, and 15 HS were included. Before and after a maximal cardiopulmonary exercise test, monocyte subsets were quantified by flow cytometry: CD14++CD16?CCR2+ (Mon1), CD14++CD16+CCR2+ (Mon2), and CD14+CD16++CCR2? (Mon3). Serum levels of IL-6 and MCP-1 were determined by ELISA. Results. Baseline distribution of Mon1-2-3 was comparable between the 3 groups. Following acute exercise, %Mon2 and %Mon3 increased significantly at the expense of a decrease in %Mon1 in HS and in CKD. This response was significantly attenuated in CHF (P < 0.05). In HS only, MCP-1 levels increased following exercise; IL-6 levels were unchanged. Circulatory power was a strong and independent predictor of the changes in Mon1 (? = ?0.461, P < 0.001) and Mon3 (? = 0.449, P < 0.001); and baseline LVEF of the change in Mon2 (? = 0.441, P < 0.001). Conclusion. The response of monocytes to acute exercise is characterized by an increase in proangiogenic and proinflammatory Mon2 and Mon3 at the expense of phagocytic Mon1. This exercise-induced monocyte subset response is mainly driven by hemodynamic changes and not by preexistent low-grade inflammation. PMID:25587208

Van Craenenbroeck, Amaryllis H.; Hoymans, Vicky Y.; Verpooten, Gert A.; Vrints, Christiaan J.; Couttenye, Marie M.; Van Craenenbroeck, Emeline M.

2014-01-01

285

Carbohydrate-protein drinks do not enhance recovery from exercise-induced muscle injury.  

PubMed

This study examined the effects of carbohydrate (CHO), carbohydrate-protein (CHO+PRO), or placebo (PLA) beverages on recovery from novel eccentric exercise. Female participants performed 30 min of downhill treadmill running (-12% grade, 8.0 mph), followed by consumption of a CHO, CHO+PRO, or PLA beverage immediately, 30, and 60 min after exercise. CHO and CHO+PRO groups (n=6 per group) consumed 1.2 g x kg body weight(-1) x hr(-1) CHO, with the CHO+PRO group consuming an additional 0.3 g x kg body weight(-1) x hr(-1) PRO. The PLA group (n=6) received an isovolumetric noncaloric beverage. Maximal isometric quadriceps strength (QUAD), lower extremity muscle soreness (SOR), and serum creatine kinase (CK) were assessed preinjury (PRE) and immediately and 1, 2, and 3 d postinjury to assess exercise-induced muscle injury and rate of recovery. There was no effect of treatment on recovery of QUAD (p= .21), SOR (p= .56), or CK (p= .59). In all groups, QUAD was reduced compared with PRE by 20.6%+/-1.5%, 17.2%+/-2.3%, and 11.3%+/-2.3% immediately, 1, and 2 d postinjury, respectively (p< .05). SOR peaked at 2 d postinjury (PRE vs. 2 d, 3.1+/-1.0 vs. 54.0+/-4.8 mm, p< .01), and serum CK peaked 1 d postinjury (PRE vs. 1 d, 138+/-47 vs. 757+/-144 U/L, p< .01). In conclusion, consuming a CHO+PRO or CHO beverage immediately after novel eccentric exercise failed to enhance recovery of exercise-induced muscle injury differently than what was observed with a PLA drink. PMID:18272930

Green, Michael S; Corona, Benjamin T; Doyle, J Andrew; Ingalls, Christopher P

2008-02-01

286

A Systematic Review of the Literature on Screening for Exercise-Induced Asthma: Considerations for School Nurses  

ERIC Educational Resources Information Center

Asthma is a major cause of illness, missed school days, and hospitalization in children. One type of asthma common in children is exercise-induced asthma (EIA). EIA causes airway narrowing with symptoms of cough and shortness of breath during exercise. The purpose of this article is to review the literature relevant to screening children and…

Worrell, Kelly; Shaw, Michele R.; Postma, Julie; Katz, Janet R.

2015-01-01

287

Exercise-induced depression of the diaphragm motor evoked potential is not affected by non-invasive ventilation  

Microsoft Academic Search

Whole body exercise is followed by a depression of the diaphragm motor evoked potential (MEP). It is unknown whether the change is due to diaphragm activity or whole body exercise. To test the hypothesis that exercise-induced MEP depression was related to diaphragm activity, we performed two experiments. The first examined the effect of whole body exercise, performed with and without

Mark J. Dayer; Sophie Jonville; Michelle Chatwin; Elisabeth B. Swallow; Raphael Porcher; Tarek Sharshar; Ewen T. Ross; Nicholas S. Hopkinson; John Moxham; Michael I. Polkey

2007-01-01

288

Level of dietary protein does not impact whole body protein turnover during an exercise induced energy deficit  

Technology Transfer Automated Retrieval System (TEKTRAN)

Introduction: This study examined the effect of a high protein diet on whole body protein turnover during an exercise-induced energy deficit. A sustained energy deficit induced by energy intake restriction increases protein catabolism which can cause lean-body mass loss. A high-protein diet has be...

289

Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function  

PubMed Central

The positive role of PARP1 in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of PARP1 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of PARP1 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of PARP1. Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Pol?), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in PARP1-depleted cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:25378300

Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor; Mitra, Sankar; Szabo, Csaba

2014-01-01

290

Opposing roles of mitochondrial and nuclear PARP1 in the regulation of mitochondrial and nuclear DNA integrity: implications for the regulation of mitochondrial function.  

PubMed

The positive role of PARP1 in regulation of various nuclear DNA transactions is well established. Although a mitochondrial localization of PARP1 has been suggested, its role in the maintenance of the mitochondrial DNA is currently unknown. Here we investigated the role of PARP1 in the repair of the mitochondrial DNA in the baseline and oxidative stress conditions. We used wild-type A549 cells or cells depleted of PARP1. Our data show that intra-mitochondrial PARP1 interacts with a key mitochondrial-specific DNA base excision repair (BER) enzymes, namely EXOG and DNA polymerase gamma (Pol?), which under oxidative stress become poly(ADP-ribose)lated (PARylated). Interaction between mitochondrial BER enzymes was significantly affected in the presence of PARP1. Moreover, the repair of the oxidative-induced damage to the mitochondrial DNA in PARP1-depleted cells was found to be more robust compared to control counterpart. In addition, mitochondrial biogenesis was enhanced in PARP1-depleted cells, including mitochondrial DNA copy number and mitochondrial membrane potential. This observation was further confirmed by analysis of lung tissue isolated from WT and PARP1 KO mice. In summary, we conclude that mitochondrial PARP1, in opposite to nuclear PARP1, exerts a negative effect on several mitochondrial-specific transactions including the repair of the mitochondrial DNA. PMID:25378300

Szczesny, Bartosz; Brunyanszki, Attila; Olah, Gabor; Mitra, Sankar; Szabo, Csaba

2014-12-01

291

Mitochondrial Dysfunction: Different Routes to Alzheimer's Disease Therapy  

PubMed Central

Mitochondria are dynamic ATP-generating organelle which contribute to many cellular functions including bioenergetics processes, intracellular calcium regulation, alteration of reduction-oxidation potential of cells, free radical scavenging, and activation of caspase mediated cell death. Mitochondrial functions can be negatively affected by amyloid ? peptide (A?), an important component in Alzheimer's disease (AD) pathogenesis, and A? can interact with mitochondria and cause mitochondrial dysfunction. One of the most accepted hypotheses for AD onset implicates that mitochondrial dysfunction and oxidative stress are one of the primary events in the insurgence of the pathology. Here, we examine structural and functional mitochondrial changes in presence of A?. In particular we review data concerning A? import into mitochondrion and its involvement in mitochondrial oxidative stress, bioenergetics, biogenesis, trafficking, mitochondrial permeability transition pore (mPTP) formation, and mitochondrial protein interaction. Moreover, the development of AD therapy targeting mitochondria is also discussed. PMID:25221640

Picone, Pasquale; Nuzzo, Domenico; Caruana, Luca; Scafidi, Valeria; Di Carlo, Marta

2014-01-01

292

Identification of mitochondrial complex I assembly intermediates by tracing tagged NDUFS3 demonstrates the entry point of mitochondrial subunits  

Microsoft Academic Search

Biogenesis of human mitochondrial complex I (CI) requires the coordinated assembly of 45 subunits derived from both the mitochondrial and nuclear genome. The presence of CI subcomplexes in CI-deficient cells suggests that assembly occurs in distinct steps. However, discriminating between products of assembly or instability is problematic. Using an inducible NDUFS3-green fluorescent protein (GFP) expression system in HEK293 cells, we

R. O. Vogel; C. E. J. Dieteren; L. P. W. J. van den Heuvel; P. H. G. M. Willems; J. A. M. Smeitink; W. J. H. Koopman; L. G. J. Nijtmans

2007-01-01

293

Chloroplast and Mitochondrial Proteases in Arabidopsis. A Proposed Nomenclature  

Microsoft Academic Search

The identity and scope of chloroplast and mitochondrial proteases in higher plants has only started to become apparent in recent years. Biochemical and molecular studies suggested the existence of Clp, FtsH, and DegP proteases in chloroplasts, and a Lon protease in mitochondria, although currently the full extent of their role in organellar biogenesis and function remains poorly understood. Rapidly accumulating

Zach Adam; Iwona Adamska; Kazumi Nakabayashi; Oren Ostersetzer; Kirsten Haussuhl; Andrea Manuell; Bo Zheng; Olivier Vallon; Steven R. Rodermel; Kazuo Shinozaki; Adrian K. Clarke

2001-01-01

294

A Mitochondria-Specific Isoform of FASTK Is Present In Mitochondrial RNA Granules and Regulates Gene Expression and Function.  

PubMed

The mitochondrial genome relies heavily on post-transcriptional events for its proper expression, and misregulation of this process can cause mitochondrial genetic diseases in humans. Here, we report that a novel translational variant of Fas-activated serine/threonine kinase (FASTK) co-localizes with mitochondrial RNA granules and is required for the biogenesis of ND6 mRNA, a mitochondrial-encoded subunit of the NADH dehydrogenase complex (complex I). We show that ablating FASTK expression in cultured cells and mice results specifically in loss of ND6 mRNA and reduced complex I activity in vivo. FASTK binds at multiple sites along the ND6 mRNA and its precursors and cooperates with the mitochondrial degradosome to ensure regulated ND6 mRNA biogenesis. These data provide insights into the mechanism and control of mitochondrial RNA processing within mitochondrial RNA granules. PMID:25704814

Jourdain, Alexis A; Koppen, Mirko; Rodley, Christopher D; Maundrell, Kinsey; Gueguen, Naïg; Reynier, Pascal; Guaras, Adela M; Enriquez, José A; Anderson, Paul; Simarro, Maria; Martinou, Jean-Claude

2015-02-24

295

Evaluation of serum leaking enzymes and investigation into new biomarkers for exercise-induced muscle damage.  

PubMed

This investigation determined whether existing muscle damage markers and organ damage markers respond to an acute eccentric exercise protocol and are associated with affected muscle symptoms. Nine healthy-young men completed one-leg calf-raise exercise with their right leg on a force plate. They performed 10 sets of 40 repetitions of exercise at 0.5 Hz with a load corresponding to half of their body weight, with 3 min rest between sets. The tenderness of medial gastrocnemius, lateral gastrocnemius and soleus, and the ankle active range of motion (ROM) were assessed before, immediately after, 24 h and 48 h, 72 h, 96 h and 168 h after exercise. Blood and urine were collected pre-exercise and 2 h, 4 h, 24 h, 48 h, 72 h and 96 h post-exercise. Serum was analyzed for creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH) and aldolase (ALD) activities. We also determined heart-type fatty acid-binding protein (H-FABP), intestinal-type fatty acid-binding protein (I-FABP) and liver-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin (IL)-17A, IL-23, nerve growth factor (NGF), soluble-Endothelial (sE)-selectin, s-Leukocyte (L)-selectin, s-Platelets (P)-selectin, and 8-isoprostane in plasma and urine. The tenderness of proximal and middle gastrocnemius increased significantly 72 h (p < 0.05, p < 0.01) after exercise. Ankle active ROM in dorsal flexion decreased significantly 48 h (p < 0.05) and 72 h (p < 0.01) after exercise. CK and ALD activities significantly increased at 72 h (p < 0.05) and remained elevated at 96 h (p < 0.01) postexercise compared to pre-exercise values. Also, ALD which showed relatively lower interindividual variability was significantly correlated with tenderness of middle gastrocnemius at 72 h. LDH activity significantly increased 96 h postexercise (p < 0.01), whereas the increase in AST and ALT activities 96 h post-exercise was not significantly different from pre-exercise values. There were no significant changes in FABPs, NGAL, IL-17A, IL-23, NGF, selectins and 8-isoprostanes in plasma and urine. In conclusion, calf-raise exercise induced severe local muscle damage symptoms which were accompanied by increases in both serum CK and ALD activities, but we could not detect any changes in examined markers of organ damage, inflammation and oxidative stress. Further research is needed to determine other more sensitive biomarkers and the underlying mechanisms of exercise-induced muscle damage. PMID:24974720

Kanda, Kazue; Sugama, Kaoru; Sakuma, Jun; Kawakami, Yasuo; Suzuki, Katsuhiko

2014-01-01

296

Dense-Core Secretory Granule Biogenesis  

NSDL National Science Digital Library

The dense-core secretory granule is a key organelle for secretion of hormones and neuropeptides in endocrine cells and neurons, in response to stimulation. Cholesterol and granins are critical for the assembly of these organelles at the trans-Golgi network, and their biogenesis is regulated quantitatively by posttranscriptional and posttranslational mechanisms.

Taeyoon Kim (National Institutes of Health Section on Cellular Neurobiology, National Institute of Child Health and Human Development)

2006-04-01

297

The effect of exercise-induced arousal on chosen tempi for familiar melodies.  

PubMed

Many previous studies have shown that arousal affects time perception, suggesting a direct influence of arousal on the speed of the pacemaker of the internal clock. However, it is unknown whether arousal influences the mental representation of tempo (speed) for highly familiar and complex stimuli, such as well-known melodies, that have long-term representations in memory. Previous research suggests that mental representations of the tempo of familiar melodies are stable over time; the aim of the present study was to investigate whether these representations can be systematically altered via an increase in physiological arousal. Participants adjusted the tempo of 14 familiar melodies in real time until they found a tempo that matched their internal representation of the appropriate tempo for that piece. The task was carried out before and after a physiologically arousing (exercise) or nonarousing (anagrams) manipulation. Participants completed this task both while hearing the melodies aloud and while imagining them. Chosen tempi increased significantly following exercise-induced arousal, regardless of whether a melody was heard aloud or imagined. These findings suggest that a change in internal clock speed affects temporal judgments even for highly familiar and complex stimuli such as music. PMID:25056004

Jakubowski, Kelly; Halpern, Andrea R; Grierson, Mick; Stewart, Lauren

2015-04-01

298

Exercise-induced hypertension among healthy firefighters-a comparison between two different definitions.  

PubMed

Different studies have yielded conflicting results regarding the association of hypertensive response to exercise and cardiovascular morbidity. We compared two different definitions of exaggerated hypertensive response to exercise and their association with cardio-respiratory fitness in a population of healthy firefighters. We examined blood pressure response to exercise in 720 normotensive male career firefighters. Fitness was measured as peak metabolic equivalent tasks (METs) achieved during maximal exercise treadmill tests. Abnormal hypertensive response was defined either as systolic blood pressure ? 200 mm Hg; or alternatively, as responses falling in the upper tertile of blood pressure change from rest to exertion, divided by the maximal workload achieved. Using the simple definition of a 200 mm Hg cutoff at peak exercise less fit individuals (METs ? 12) were protected from an exaggerated hypertensive response (OR 0.45, 95%CI 0.30-0.67). However, using the definition of exercise-induced hypertension that corrects for maximal workload, less fit firefighters had almost twice the risk (OR 1.8, 95%CI 1.3-2.47). Blood pressure change corrected for maximal workload is better correlated with cardiorespiratory fitness. Systolic blood pressure elevation during peak exercise likely represents an adaptive response, whereas elevation out of proportion to the maximal workload may indicate insufficient vasodilation and a maladaptive response. Prospective studies are needed to best define exaggerated blood pressure response to exercise. PMID:23246464

Leiba, Adi; Baur, Dorothee M; Kales, Stefanos N

2013-01-01

299

Topical cooling (icing) delays recovery from eccentric exercise-induced muscle damage.  

PubMed

It is generally thought that topical cooling can interfere with blood perfusion and may have positive effects on recovery from a traumatic challenge. This study examined the influence of topical cooling on muscle damage markers and hemodynamic changes during recovery from eccentric exercise. Eleven male subjects (age 20.2 ± 0.3 years) performed 6 sets of elbow extension at 85% maximum voluntary load and randomly assigned to topical cooling or sham groups during recovery in a randomized crossover fashion. Cold packs were applied to exercised muscle for 15 minutes at 0, 3, 24, 48, and 72 hours after exercise. The exercise significantly elevated circulating creatine kinase-MB isoform (CK-MB) and myoglobin levels. Unexpectedly, greater elevations in circulating CK-MB and myoglobin above the control level were noted in the cooling trial during 48-72 hours of the post-exercise recovery period. Subjective fatigue feeling was greater at 72 hours after topical cooling compared with controls. Removal of the cold pack also led to a protracted rebound in muscle hemoglobin concentration compared with controls. Measures of interleukin (IL)-8, IL-10, IL-1?, and muscle strength during recovery were not influenced by cooling. A peak shift in IL-12p70 was noted during recovery with topical cooling. These data suggest that topical cooling, a commonly used clinical intervention, seems to not improve but rather delay recovery from eccentric exercise-induced muscle damage. PMID:22820210

Tseng, Ching-Yu; Lee, Jo-Ping; Tsai, Yung-Shen; Lee, Shin-Da; Kao, Chung-Lan; Liu, Te-Chih; Lai, Cheng- Hsiu; Harris, M Brennan; Kuo, Chia-Hua

2013-05-01

300

Pulmonary inflammation due to exercise-induced pulmonary haemorrhage in Thoroughbred colts during race training.  

PubMed

This study investigated the putative roles of inflammation and platelet-activating factor (PAF) in exercise-induced pulmonary haemorrhage (EIPH). Two-year-old Thoroughbred colts (n=37) were exercised on a racetrack for 5months before commencement of the study. Each colt was then exercised at 15-16m/s over 800-1000m and broncho-alveolar lavage fluid (BALF) was collected 24h later. The colts were subsequently divided into two groups on the basis of BALF analysis; an EIPH-positive group (presence of haemosiderophages, n=23) and an EIPH-negative group (absence of haemosiderophages, n=14). BALF from the EIPH-positive group had a significantly higher protein concentration (0.39±0.28 vs. 0.19±0.12mg/mL, P=0.031), higher PAF bioactivity (0.18±0.12 vs. 0.043±0.05 340:380nm ratio, P=0.042) and a higher lipid hydroperoxide concentration compared to the EIPH-negative group. There was also a lower nitrite concentration and reduced production of superoxide anion and hydrogen peroxide by alveolar macrophages in the EIPH-positive group. There was evidence of pulmonary inflammation and a decreased innate immune response of alveolar macrophages in EIPH-positive colts compared with the EIPH-negative group. PMID:22108190

Michelotto, Pedro V; Muehlmann, Luis A; Zanatta, Ana L; Bieberbach, Eloyse W R; Kryczyk, Marcelo; Fernandes, Luis C; Nishiyama, Anita

2011-11-01

301

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin.  

PubMed

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood-brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L C; Ching, Yick Pang; Christie, Brian R; Lee, Tatia M C; Xu, Aimin; So, Kwok-Fai

2014-11-01

302

Physical exercise-induced hippocampal neurogenesis and antidepressant effects are mediated by the adipocyte hormone adiponectin  

PubMed Central

Adiponectin (ADN) is an adipocyte-secreted protein with insulin-sensitizing, antidiabetic, antiinflammatory, and antiatherogenic properties. Evidence is also accumulating that ADN has neuroprotective activities, yet the underlying mechanism remains elusive. Here we show that ADN could pass through the blood–brain barrier, and elevating its levels in the brain increased cell proliferation and decreased depression-like behaviors. ADN deficiency did not reduce the basal hippocampal neurogenesis or neuronal differentiation but diminished the effectiveness of exercise in increasing hippocampal neurogenesis. Furthermore, exercise-induced reduction in depression-like behaviors was abrogated in ADN-deficient mice, and this impairment in ADN-deficient mice was accompanied by defective running-induced phosphorylation of AMP-activated protein kinase (AMPK) in the hippocampal tissue. In vitro analyses indicated that ADN itself could increase cell proliferation of both hippocampal progenitor cells and Neuro2a neuroblastoma cells. The neurogenic effects of ADN were mediated by the ADN receptor 1 (ADNR1), because siRNA targeting ADNR1, but not ADNR2, inhibited the capacity of ADN to enhance cell proliferation. These data suggest that adiponectin may play a significant role in mediating the effects of exercise on hippocampal neurogenesis and depression, possibly by activation of the ADNR1/AMPK signaling pathways, and also raise the possibility that adiponectin and its agonists may represent a promising therapeutic treatment for depression. PMID:25331877

Yau, Suk Yu; Li, Ang; Hoo, Ruby L. C.; Ching, Yick Pang; Christie, Brian R.; Lee, Tatia M. C.; Xu, Aimin; So, Kwok-Fai

2014-01-01

303

Could a vegetarian diet reduce exercise-induced oxidative stress? A review of the literature.  

PubMed

Oxidative stress is a natural physiological process that describes an imbalance between free radical production and the ability of the antioxidant defence system of the body to neutralize free radicals. Free radicals can be beneficial as they may promote wound healing and contribute to a healthy immune response. However, free radicals can have a detrimental impact when they interfere with the regulation of apoptosis and thus play a role in the promotion of some cancers and conditions such as cardiovascular disease. Antioxidants are molecules that reduce the damage associated with oxidative stress by counteracting free radicals. Regular exercise is a vital component of a healthy lifestyle, although it can increase oxidative stress. As a typical vegetarian diet comprises a wide range of antioxidant-rich foods, it is plausible that the consumption of these foods will result in an enhanced antioxidant system capable of reducing exercise-induced oxidative stress. In addition, a relationship between a vegetarian diet and lower risks of cardiovascular disease and some cancers has been established. This review explores the current available evidence linking exercise, vegetarians, antioxidants, and oxidative stress. PMID:20845212

Trapp, Denise; Knez, Wade; Sinclair, Wade

2010-10-01

304

Exercise Effects on Erythrocyte Deformability in Exercise-induced Arterial Hypoxemia.  

PubMed

Exercise-induced arterial hypoxemia (EIAH) is often found in endurance-trained subjects at high exercise intensity. The role of erythrocyte deformability (ED) in EIAH has been scarcely explored. We aimed to explore the role of erythrocyte properties and lactate accumulation in the response of ED in EIAH. ED was determined in 10 sedentary and in 16 trained subjects, both before and after a maximal incremental test, and after recovery, along with mean corpuscular volume (MCV) and red blood cell lactate concentrations. EIAH was found in 6 trained subjects (?SaO2=-8.25±4.03%). Sedentary and non-EIAH trained subjects showed reduced ED after exercise, while no effect on ED was found in EIAH trained subjects. After exercise, lactate concentrations rose and MCV increased equally in all groups. ED is strongly driven by cell volume, but the different ED response to exercise in EIAH shows that other cellular mechanisms may be implicated. Interactions between membrane and cytoskeleton, which have been found to be O2-regulated, play a role in ED. The drop in SaO2 in EIAH subjects can improve ED response to exercise. This can be an adaptive mechanism that enhances muscular and pulmonary perfusion, and allows the achievement of high exercise intensity in EIAH despite lower O2 arterial transport. PMID:25429547

Alis, R; Sanchis-Gomar, F; Ferioli, D; Torre, A La; Blesa, J R; Romagnoli, M

2015-04-01

305

Assessment of Eccentric Exercise-Induced Oxidative Stress Using Oxidation-Reduction Potential Markers  

PubMed Central

The aim of the present study was to investigate the use of static (sORP) and capacity ORP (cORP) oxidation-reduction potential markers as measured by the RedoxSYS Diagnostic System in plasma, for assessing eccentric exercise-induced oxidative stress. Nineteen volunteers performed eccentric exercise with the knee extensors. Blood was collected before, immediately after exercise, and 24, 48, and 72?h after exercise. Moreover, common redox biomarkers were measured, which were protein carbonyls, thiobarbituric acid-reactive substances, total antioxidant capacity in plasma, and catalase activity and glutathione levels in erythrocytes. When the participants were examined as one group, there were not significant differences in any marker after exercise. However, in 11 participants there was a high increase in cORP after exercise, while in 8 participants there was a high decrease. Thus, the participants were divided in low cORP group exhibiting significant decrease in cORP after exercise and in high cORP group exhibiting significant increase. Moreover, only in the low cORP group there was a significant increase in lipid peroxidation after exercise suggesting induction of oxidative stress. The results suggested that high decreases in cORP values after exercise may indicate induction of oxidative stress by eccentric exercise, while high increases in cORP values after exercise may indicate no existence of oxidative stress. PMID:25874019

Stagos, Dimitrios; Goutzourelas, Nikolaos; Ntontou, Amalia-Maria; Kafantaris, Ioannis; Deli, Chariklia K.; Poulios, Athanasios; Jamurtas, Athanasios Z.; Bar-Or, David; Kouretas, Dimitrios

2015-01-01

306

Exercise-induced oxygen desaturation in COPD patients without resting hypoxemia.  

PubMed

Exercise-induced oxygen desaturation (EID) is associated with increased risk of mortality in chronic obstructive pulmonary disease (COPD). Several screening tests have been proposed to predict EID, including FEV1, DLCO and baseline-SpO2. We aimed to validate a proposed cut-off of baseline-SpO2 ?95% as simple screening procedure to predict EID during six-minute walk test (6MWT). In addition, we studied the prevalence and characteristics of patients exhibited EID to SpO2nadir ?88%. 402 non-hypoxemic COPD patients performed 6MWT. Sensitivity and specificity of baseline SpO2 ?95% as a cut-off to predict EID and determinants of EID were investigated. 158 patients (39%) exhibited EID. The sensitivity of baseline-SpO2 ?95% to predict EID was 81.0%, specificity 49.2%, positive and negative predictive values were 50.8% and 80.0%, respectively. In a multivariate model, DLCO <50%, FEV1 <45%, PaO2 <10kPa, baseline-SpO2 <95%, and female sex were the strongest determinants of EID. Baseline oxygen saturation solely is inaccurate to predict EID. A combination of clinical characteristics (DLCO, FEV1, PaO2, baseline-SpO2, sex) increases the odds for EID in COPD. PMID:24121092

Andrianopoulos, Vasileios; Franssen, Frits M E; Peeters, Jos P I; Ubachs, Tim J A; Bukari, Halah; Groenen, Miriam; Burtin, Chris; Vogiatzis, Ioannis; Wouters, Emiel F M; Spruit, Martijn A

2014-01-01

307

Exercise-Induced Changes in Iron Status and Hepcidin Response in Female Runners  

PubMed Central

Background and Aims Exercise-induced iron deficiency is a common finding in endurance athletes. It has been suggested recently that hepcidin may be an important mediator in this process. Objective To determine hepcidin levels and markers of iron status during long-term exercise training in female runners with depleted and normal iron stores. Methods Fourteen runners were divided into two groups according to iron status. Blood samples were taken during a period of eight weeks at baseline, after training and after ten days’ recovery phase. Results Of 14 runners, 7 were iron deficient at baseline and 10 after training. Hepcidin was lower at recovery compared with baseline (p<0.05). The mean cell haemoglobin content, haemoglobin content per reticulocyte and total iron binding capacity all decreased, whereas soluble transferrin receptor and hypochromic red cells increased after training and recovery (p<0.05 for all). Conclusion The prevalence of depleted iron stores was 71% at the end of the training phase. Hepcidin and iron stores decreased during long-term running training and did not recover after ten days, regardless of baseline iron status. PMID:23472137

Auersperger, Irena; Škof, Branko; Leskošek, Bojan; Knap, Bojan; Jerin, Aleš; Lainscak, Mitja

2013-01-01

308

Cold- and exercise-induced peak metabolic rates in tropical birds  

PubMed Central

Compared with temperate birds, tropical birds have low reproductive rates, slow development as nestlings, and long lifespans. These “slow” life history traits are thought to be associated with reduced energy expenditure, or a slow “pace of life.” To test predictions from this hypothesis, we measured exercise-induced peak metabolic rates (PMRE) in 45 species of tropical lowland forest birds and compared these data with PMRE for three temperate species. We also compared cold-induced PMR (PMRC) with PMRE in the same individuals of 19 tropical species. Tropical birds had a 39% lower PMRE than did the temperate species. In tropical birds, PMRC and PMRE scaled similarly with body mass (Mb), but PMRE was 47% higher than PMRC. PMRE averaged 6.44 × basal metabolic rate (BMR) and PMRC averaged 4.52 × BMR. The slope of the equation relating PMRE to Mb exceeded the slope for the equation for BMR vs. Mb, whereas slopes for the equations of PMRC and BMR vs. Mb did not differ. Mb-adjusted residuals of PMRE were positively correlated with residual BMR, whereas residual PMRC and residual BMR were not correlated. PMRE and PMRC were not correlated after we corrected for Mb. Temperate birds maintained their body temperature at an 8.6°C lower average air temperature than did tropical species. The lower PMRE values in tropical species suggest that their suite of life history traits on the slow end of the life history continuum are associated with reduced metabolic rates. PMID:18093954

Wiersma, Popko; Chappell, Mark A.; Williams, Joseph B.

2007-01-01

309

Impact of an endurance training program on exercise-induced cardiac biomarker release.  

PubMed

We evaluated the influence of a 14-wk endurance running program on the exercise-induced release of high-sensitivity cardiac troponin T (hs-cTnT) and NH2-terminal pro-brain natriuretic peptide (NT-proBNP). Fifty-eight untrained participants were randomized to supervised endurance exercise (14 wk, 3-4 days/wk, 120-240 min/wk, 65-85% of maximum heart rate) or a control group. At baseline and after the training program, hs-cTnT and NT-proBNP were assessed before and 5 min, 1 h, 3 h, 6 h, 12 h, and 24 h after a 60-min maximal running test. Before training, hs-cTnT was significantly elevated in both groups with acute exercise (P < 0.0001) with no between-group differences. There was considerable heterogeneity in peak hs-cTnT concentration with the upper reference limit exceeded in 71% of the exercise tests. After training, both baseline and postexercise hs-cTnT were significantly higher compared with pretraining and the response of the control group (P = 0.008). Acute exercise led to a small but significant increase in NT-proBNP, but this was not mediated by training (P = 0.121). In summary, a controlled endurance training intervention resulted in higher pre- and postexercise values of hs-cTnT with no changes in NT-proBNP. PMID:25681432

Legaz-Arrese, Alejandro; López-Laval, Isaac; George, Keith; Puente-Lanzarote, Juan José; Mayolas-Pi, Carmen; Serrano-Ostáriz, Enrique; Revilla-Martí, Pablo; Moliner-Urdiales, Diego; Reverter-Masià, Joaquín

2015-04-15

310

Exercise-induced dehydration does not alter time trial or neuromuscular performance.  

PubMed

This study examined the effect of exercise-induced dehydration by ~4% body mass loss on 5-km cycling time trial (TT) performance and neuromuscular drive, independent of hyperthermia. 7 active males were dehydrated on 2 occasions, separated by 7 d. Participants remained dehydrated (DEH, -3.8±0.5%) or were rehydrated (REH, 0.2±0.6%) over 2?h before completing the TT at 18-25?°C, 20-30% relative humidity. Neuromuscular function was determined before dehydration and immediately prior the TT. The TT started at the same core temperature (DEH, 37.3±0.3°C; REH, 37.0±0.2?°C (P>0.05). Neither TT performance (DEH, 7.31±1.5?min; REH, 7.10±1.3?min (P>0.05)) or % voluntary activation were affected by dehydration (DEH, 88.7±6.4%; REH, 90.6±6.1% (P>0.05)). Quadriceps peak torque was significantly elevated in both trials prior to the TT (P<0.05), while a 19% increase in the rate of potentiated peak twitch torque development (P<0.05) was observed in the DEH trial only. All other neuromuscular measures were similar between trials. Short duration TT performance and neuromuscular function are not reduced by dehydration, independent of hyperthermia. PMID:24577860

Stewart, C J; Whyte, D G; Cannon, J; Wickham, J; Marino, F E

2014-08-01

311

Astragalus membranaceus improves exercise performance and ameliorates exercise-induced fatigue in trained mice.  

PubMed

Astragalus membranaceus (AM) is a popular "Qi-tonifying" herb with a long history of use as a Traditional Chinese Medicine with multiple biological functions. However, evidence for the effects of AM on exercise performance and physical fatigue is limited. We evaluated the potential beneficial effects of AM on ergogenic and anti-fatigue functions following physiological challenge. Male ICR strain mice were randomly assigned to four groups (n = 10 per group) for treatment: (1) sedentary control and vehicle treatment (vehicle control); (2) exercise training with vehicle treatment (exercise control); and (3) exercise training with AM treatment at 0.615 g/kg/day (Ex-AM1) or (4) 3.075 g/kg/day (Ex-AM5). Both the vehicle and AM were orally administered for 6 weeks. Exercise performance and anti-fatigue function were evaluated by forelimb grip strength, exhaustive swimming time, and levels of serum lactate, ammonia, glucose, and creatine kinase after 15-min swimming exercise. Exercise training combined with AM supplementation increased endurance exercise capacity and increased hepatic and muscle glycogen content. AM reduced exercise-induced accumulation of the byproducts blood lactate and ammonia with acute exercise challenge. Moreover, we found no deleterious effects from AM treatment. Therefore, AM supplementation improved exercise performance and had anti-fatigue effects in mice. It may be an effective ergogenic aid in exercise training. PMID:24595275

Yeh, Tzu-Shao; Chuang, Hsiao-Li; Huang, Wen-Ching; Chen, Yi-Ming; Huang, Chi-Chang; Hsu, Mei-Chich

2014-01-01

312

Section 2. Exercise-Induced Bronchospasm: Albuterol versus Montelukast: Highlights of the Asthma Summit 2009: Beyond the Guidelines  

PubMed Central

Exercise-induced bronchospasm (EIB) involves airway obstruction with an onset shortly after exercising. It can occur in individuals without a diagnosis of asthma, but is most common in asthmatic patients (and in this scenario may be referred to as exercise-induced asthma, EIA), correlating with the patient's degree of airway hyperreactivity. While albuterol is the most commonly used rescue and prophylactic medication for EIB, the leukotriene antagonist, monetlukast, may be an appropriate choice for some patients. Clinical data have shown that once-daily treatment with montelukast (5 or 10 mg tablet) can offer protection against EIB within 3 days for some patients. Such an approach might be preferred for patients who have difficulty with inhaled medications and for children who cannot access their inhalers during the school day. Montelukast also may be an option to reduce side effects associated with albuterol for individuals who exercise regularly. PMID:24228852

2010-01-01

313

A low dose of alcohol does not impact skeletal muscle performance after exercise-induced muscle damage  

Microsoft Academic Search

Moderate, acute alcohol consumption after eccentric exercise has been shown to magnify the muscular weakness that is typically\\u000a associated with exercise-induced muscle damage (EIMD). As it is not known whether this effect is dose-dependent, the aim of\\u000a this study was to investigate the effect of a low dose of alcohol on EIMD-related losses in muscular performance. Ten healthy\\u000a males performed

Matthew J. Barnes; Toby Mündel; Stephen R. Stannard

2011-01-01

314

Effects of eccentric exercise-induced muscle injury on blood levels of platelet activating factor (PAF) and other inflammatory markers  

Microsoft Academic Search

It has been reported that exercise with eccentric contractions can induce damage and inflammation in human muscle tissue,\\u000a the severity of which depends on the duration and the intensity of exercise. Platelet activating factor (PAF) is a potent\\u000a inflammatory mediator implicated in a series of pathophysiological conditions. We sought to investigate the relationship between\\u000a PAF and eccentric exercise induced muscle

George A. Milias; Tzortzis Nomikos; Elizabeth Fragopoulou; Spyridon Athanasopoulos; Smaragdi Antonopoulou

2005-01-01

315

Exercise Induced Left Bundle Branch Block Treated with Cardiac Rehabilitation: A Case Report and a Review of the Literature  

PubMed Central

Exercise induced bundle branch block is a rare observation in exercise testing, accounting for 0.5 percent of exercise tests. The best treatment of this condition and its association with coronary disease remain unclear. We describe a case associated with normal coronary arteries which was successfully treated with exercise training. While this treatment has been used previously, our case has a longer followup than previously reported and demonstrates that the treatment is not durable in the absence of continued exercise. PMID:24716091

Anderson, Nathan S.; Ramirez, Alexies; Slim, Ahmad; Malik, Jamil

2014-01-01

316

Lack of an association between T-wave alternans and ST-segment depression during exercise-induced ambulatory ischemia  

Microsoft Academic Search

It is known that T-wave alternans (TWA), which identify patients at risk for arrhythmic events, often occur during acute coronary occlusion in association with ST-segment elevation. To test the hypothesis that TWA is associated with a certain state\\/severity of myocardial infarction\\/ischemia, we assessed the association between TWA and ST-segment depression during exercise-induced ambulatory ischemia. Of 351 consecutive patients with coronary

Takanori Ikeda; Kenta Kumagai; Mitsuaki Takami; Naoki Tezuka; Takeshi Nakae; Takao Sakata; Mahito Noro; Yoshihisa Enjoji; Kaoru Sugi; Tetsu Yamaguchi

2000-01-01

317

Recording locations in multichannel magnetocardiography and body surface potential mapping sensitive for regional exercise-induced myocardial ischemia  

Microsoft Academic Search

Introduction This study aimed to identify the optimal locations in multichannel magnetocardiography (MCG) and body surface potential mapping\\u000a (BSPM) to detect exercise-induced myocardial ischemia. Methods We studied 17 healthy controls and 24 coronary artery disease (CAD) patients with stenosis in one of the main coronary artery\\u000a branches: left anterior descending (LAD) in 11 patients, right (RCA) in 7 patients, and

Helena Hänninen; Panu Takala; Markku Mäkijärvi; Juha Montonen; Petri Korhonen; Lasse Oikarinen; Kim Simelius; Jukka Nenonen; Toivo Katila; Lauri Toivonen

2001-01-01

318

The dynamics of physical exercise-induced increases in thalamic and abdominal temperatures are modified by central cholinergic stimulation.  

PubMed

Evidence has shown that brain and abdominal (Tabd) temperatures are regulated by distinct physiological mechanisms. Thus, the present study examined whether central cholinergic stimulation would change the dynamics of exercise-induced increases in Tabd and thalamic temperature (Tthal), an index of brain temperature. Adult male Wistar rats were used in all of the experiments. Two guide cannulae were implanted in the rats, one in the thalamus and the other in the right lateral cerebral ventricle, to measure Tthal and to centrally inject a cholinergic agonist, respectively. Then, a temperature sensor was implanted in the abdominal cavity. On the day of the experiments, the rats received an intracerebroventricular injection of 2?L of 10(-2)M physostigmine (Phy) or a vehicle solution (Veh) and were subjected to treadmill running until volitional fatigue occurred. Tthal was measured using a thermistor connected to a multimeter, and Tabd was recorded by telemetry. Phy injection delayed the exercise-induced increases in Tthal (37.6±0.2°C Phy vs 38.7±0.1°C Veh at the 10th min of exercise) and in Tabd. Despite the delayed hyperthermia, Phy did not change the rats' physical performance. In addition, the more rapid exercise-induced increase in Tthal relative to Tabd in the rats treated with Veh was abolished by Phy. Collectively, our data indicate that central cholinergic stimulation affects the dynamics of exercise-induced increases in Tthal and Tabd. These results also provide evidence of the involvement of cholinoceptors in the modulation of brain heat loss during physical exercise. PMID:25655022

Damasceno, William Coutinho; Pires, Washington; Lima, Milene Rodrigues Malheiros; Lima, Nilo Resende Viana; Wanner, Samuel Penna

2015-03-17

319

The role of the bronchial provocation challenge tests in the diagnosis of exercise-induced bronchoconstriction in elite swimmers  

Microsoft Academic Search

BackgroundThe International Olympic Committee–Medical Commission (IOC-MC) accepts a number of bronchial provocation tests for the diagnosis of exercise-induced bronchoconstriction (EIB) in elite athletes, none of which have been studied in elite swimmers. With the suggestion of a different pathogenesis involved in the development of EIB in swimmers, there is a possibility that the recommended test for EIB in elite athletes,

A. Castricum; K. Holzer; P. Brukner; L. Irving

2010-01-01

320

Contribution of the exercise-induced increment in glucose storage to the increased insulin sensitivity of endurance athletes  

Microsoft Academic Search

Summary  The present study was designed to evaluate the contribution of the exercise-induced increment in glucose storage to the increased\\u000a insulin sensitivity characterizing endurance athletes. Plasma glucose and insulin were measured during an oral glucose tolerance\\u000a test (OGTT) in six endurance athletes. Glucose storage and lipid oxidation during this test were also determined using indirect\\u000a calorimetry. These measurements were compared to

Angelo Tremblay; Elisabeth Fontaine; André Nadeau

1985-01-01

321

Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma  

Microsoft Academic Search

Objective: To determine whether montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction (EIB) in 6- to 14-year-old children with asthma.Study design: Double-blind, multicenter, 2-period crossover study. Children (n = 27) with forced expiratory volume in 1 second (FEV1 ) ?70% of the predicted value and a fall in FEV1 ? 20% after exercise on 2 occasions. Patients received montelukast (5-mg

James P. Kemp; Robert J. Dockhorn; Gail G. Shapiro; Ha H. Nguyen; Theodore F. Reiss; Beth C. Seidenberg; Barbara Knorr

1998-01-01

322

Exercise-induced bronchoconstriction in children: Montelukast attenuates the immediate-phase and late-phase responses  

Microsoft Academic Search

Background: Montelukast, a leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. We and others have shown that there is a late-phase response 3 to 8 hours after exercise in a subset of asthmatic patients. Objective: We sought to evaluate the protective effect of montelukast on immediate-phase and late-phase responses after exercise challenges. Methods: Twenty-two atopic asthmatic children aged 7 to 16 years

Raul E. Melo; Dirceu Solé; Charles K. Naspitz

2003-01-01

323

Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver.  

PubMed

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the US and many western countries. It is well known that APAP induces mitochondrial damage to trigger centrilobular necrosis. Emerging evidence suggests that autophagic removal of damaged mitochondria may protect against APAP-induced liver injury. Electron and confocal microscopy analysis of liver tissues revealed that APAP overdose triggers unique biochemical and pathological zonated changes in the mouse liver, which includes necrosis (zone 1), mitochondrial spheroid formation (zone 2), autophagy (zone 3) and mitochondrial biogenesis (zone 4). In this graphic review, we discuss the role of autophagy/mitophagy in limiting the expansion of necrosis and promoting mitochondrial biogenesis and liver regeneration for the recovery of APAP-induced liver injury. We also discuss possible mechanisms that could be involved in regulating APAP-induced autophagy/mitophagy and the formation of mitochondrial spheroids. PMID:24191236

Ni, Hong-Min; Williams, Jessica A; Jaeschke, Hartmut; Ding, Wen-Xing

2013-01-01

324

Zonated induction of autophagy and mitochondrial spheroids limits acetaminophen-induced necrosis in the liver?  

PubMed Central

Acetaminophen (APAP) overdose is the most frequent cause of acute liver failure in the US and many western countries. It is well known that APAP induces mitochondrial damage to trigger centrilobular necrosis. Emerging evidence suggests that autophagic removal of damaged mitochondria may protect against APAP-induced liver injury. Electron and confocal microscopy analysis of liver tissues revealed that APAP overdose triggers unique biochemical and pathological zonated changes in the mouse liver, which includes necrosis (zone 1), mitochondrial spheroid formation (zone 2), autophagy (zone 3) and mitochondrial biogenesis (zone 4). In this graphic review, we discuss the role of autophagy/mitophagy in limiting the expansion of necrosis and promoting mitochondrial biogenesis and liver regeneration for the recovery of APAP-induced liver injury. We also discuss possible mechanisms that could be involved in regulating APAP-induced autophagy/mitophagy and the formation of mitochondrial spheroids. PMID:24191236

Ni, Hong-Min; Williams, Jessica A; Jaeschke, Hartmut; Ding, Wen-Xing

2013-01-01

325

Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders.  

PubMed

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases. PMID:25519239

Aiyar, Raeka S; Bohnert, Maria; Duvezin-Caubet, Stéphane; Voisset, Cécile; Gagneur, Julien; Fritsch, Emilie S; Couplan, Elodie; von der Malsburg, Karina; Funaya, Charlotta; Soubigou, Flavie; Courtin, Florence; Suresh, Sundari; Kucharczyk, Roza; Evrard, Justine; Antony, Claude; St Onge, Robert P; Blondel, Marc; di Rago, Jean-Paul; van der Laan, Martin; Steinmetz, Lars M

2014-01-01

326

Mitochondrial protein sorting as a therapeutic target for ATP synthase disorders  

PubMed Central

Mitochondrial diseases are systemic, prevalent and often fatal; yet treatments remain scarce. Identifying molecular intervention points that can be therapeutically targeted remains a major challenge, which we confronted via a screening assay we developed. Using yeast models of mitochondrial ATP synthase disorders, we screened a drug repurposing library, and applied genomic and biochemical techniques to identify pathways of interest. Here we demonstrate that modulating the sorting of nuclear-encoded proteins into mitochondria, mediated by the TIM23 complex, proves therapeutic in both yeast and patient-derived cells exhibiting ATP synthase deficiency. Targeting TIM23-dependent protein sorting improves an array of phenotypes associated with ATP synthase disorders, including biogenesis and activity of the oxidative phosphorylation machinery. Our study establishes mitochondrial protein sorting as an intervention point for ATP synthase disorders, and because of the central role of this pathway in mitochondrial biogenesis, it holds broad value for the treatment of mitochondrial diseases. PMID:25519239

Aiyar, Raeka S.; Bohnert, Maria; Duvezin-Caubet, Stéphane; Voisset, Cécile; Gagneur, Julien; Fritsch, Emilie S.; Couplan, Elodie; von der Malsburg, Karina; Funaya, Charlotta; Soubigou, Flavie; Courtin, Florence; Suresh, Sundari; Kucharczyk, Roza; Evrard, Justine; Antony, Claude; St.Onge, Robert P.; Blondel, Marc; di Rago, Jean-Paul; van der Laan, Martin; Steinmetz, Lars M.

2014-01-01

327

Mitochondrial Homeostasis Molecules: Regulation by a Trio of Recessive Parkinson's Disease Genes  

PubMed Central

Mitochondria are small organelles that produce the majority of cellular energy as ATP. Mitochondrial dysfunction has been implicated in the pathogenesis of Parkinson's disease (PD), and rare familial forms of PD provide valuable insight into the pathogenic mechanism underlying mitochondrial impairment, even though the majority of PD cases are sporadic. The regulation of mitochondria is crucial for the maintenance of energy-demanding neuronal functions in the brain. Mitochondrial biogenesis and mitophagic degradation are the major regulatory pathways that preserve optimal mitochondrial content, structure and function. In this mini-review, we provide an overview of the mitochondrial quality control mechanisms, emphasizing regulatory molecules in mitophagy and biogenesis that specifically interact with the protein products of three major recessive familial PD genes, PINK1, Parkin and DJ-1. PMID:25548534

Han, Ji-Young; Kim, Ji-Soo

2014-01-01

328

The effects of nitroglycerin on exercise-induced regional myocardial contractile dysfunction are not diminished by pretreatment with dihydroergotamine.  

PubMed Central

1 Because controversy exists regarding the effects of dihydroergotamine (DHE) on the performance of underperfused myocardium, the effects of DHE were investigated in a model of exercise-induced regional myocardial dysfunction in conscious dogs. 2 We also investigated a possible functional antagonism between DHE and nitroglycerin that might reduce the latter drug's antianginal efficacy. 3 Investigations were carried out in conscious dogs. After stenosis of the circumflex branch of the left coronary artery that minimally affected resting myocardial function, treadmill exercise induced transient regional contractile dysfunction. Heart rate, arterial blood pressure, left ventricular dp/dtmax and left ventricular end-diastolic pressure were registered. Regional contractile performance was assessed by ultrasonic distance measurement in the underperfused and in a normally perfused area. 4 DHE (5 micrograms kg-1, i.v.) induced a decrease in left ventricular dp/dtmax at rest and during exercise. DHE did not cause a deterioration in contractile function in the ischaemic myocardium, but led to a slight although not significant improvement in regional myocardial function. 5 After pretreatment with DHE, infusion of nitroglycerin (15 micrograms kg-1, i.v.) induced an improvement in the underperfused myocardial area during treadmill exercise, accompanied by a decrease in diastolic arterial pressure and left ventricular end-diastolic pressure and an increase in left ventricular dp/dtmax. 6 These results suggest that DHE will not worsen exercise-induced angina pectoris, and that the antianginal efficacy of nitroglycerin will not be neutralized by pretreatment with DHE. PMID:3117154

Schneider, W.; Krumpl, G.; Mayer, N.; Raberger, G.

1987-01-01

329

Food-dependent exercise-induced anaphylaxis occurred only in a warm but not in a cold environment  

PubMed Central

Food-dependent exercise-induced anaphylaxis (FDEIA) is a type of exercise-induced anaphylaxis associated with postprandial exercise. We describe a 19-year-old man with FDEIA. Our patient complained of urticaria, angioedema, dizziness and hypotension associated with exercise after ingestion of walnut-containing foods in a warm environment. Skin prick test and prick to prick test were positive for walnut antigen. The attack didn't occur by free running outside for 10 min 2 h after taking walnuts, and the temperature was about -2?. Food-exercise test was done again in a warm environment based on prior history. Anaphylaxis was developed after exercise for 10 min in a warm environment after taking walnuts. Some environmental factors such as high temperature and high humidity or cold temperature may influence exercise-induced anaphylaxis. In our case, the cofactor was a warm environment: the challenge test done in a cold environment was negative, but positive in a warm environment. Physicians should be aware that the challenge test of FDEIA can show different results depending on temperature. PMID:22701867

Jo, Eun-Jung; Yang, Min-Suk; Kim, Yoon-Jeong; Kim, Hyun-Suk; Kim, Mi-Yeong; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

2012-01-01

330

Molecular mechanisms of cytochrome c biogenesis: three distinct systems.  

PubMed

The past 10 years have heralded remarkable progress in the understanding of the biogenesis of c-type cytochromes. The hallmark of c-type cytochrome synthesis is the covalent ligation of haem vinyl groups to two cysteinyl residues of the apocytochrome (at a Cys-Xxx-Yyy-Cys-His signature motif). From genetic, genomic and biochemical studies, it is clear that three distinct systems have evolved in nature to assemble this ancient protein. In this review, common principles of assembly for all systems and the molecular mechanisms predicted for each system are summarized. Prokaryotes, plant mitochondria and chloroplasts use either system I or II, which are each predicted to use dedicated mechanisms for haem delivery, apocytochrome ushering and thioreduction. Accessory proteins of systems I and II co-ordinate the positioning of these two substrates at the membrane surface for covalent ligation. The third system has evolved specifically in mitochondria of fungi, invertebrates and vertebrates. For system III, a pivotal role is played by an enzyme called cytochrome c haem lyase (CCHL) in the mitochondrial intermembrane space. PMID:9720859

Kranz, R; Lill, R; Goldman, B; Bonnard, G; Merchant, S

1998-07-01

331

Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist  

Microsoft Academic Search

BACKGROUND: A study was undertaken to determine whether montelukast, a new potent cysteinyl leukotriene receptor antagonist, attenuates exercise-induced bronchoconstriction. The relationship between the urinary excretion of LTE4 and exercise-induced bronchoconstriction was also investigated. METHODS: Nineteen non-smoking asthmatic patients with a forced expiratory volume in one second (FEV1) of > or = 65% of the predicted value and a reproducible fall

T. F. Reiss; J. B. Hill; E. Harman; J. Zhang; W. K. Tanaka; E. Bronsky; D. Guerreiro; L. Hendeles

1997-01-01

332

Curli biogenesis: order out of disorder.  

PubMed

Many bacteria assemble extracellular amyloid fibers on their cell surface. Secretion of proteins across membranes and the assembly of complex macromolecular structures must be highly coordinated to avoid the accumulation of potentially toxic intracellular protein aggregates. Extracellular amyloid fiber assembly poses an even greater threat to cellular health due to the highly aggregative nature of amyloids and the inherent toxicity of amyloid assembly intermediates. Therefore, temporal and spatial control of amyloid protein secretion is paramount. The biogenesis and assembly of the extracellular bacterial amyloid curli is an ideal system for studying how bacteria cope with the many challenges of controlled and ordered amyloid assembly. Here, we review the recent progress in the curli field that has made curli biogenesis one of the best-understood functional amyloid assembly pathways. This article is part of a Special Issue entitled: Protein trafficking and secretion in bacteria. Guest Editors: Anastassios Economou and Ross Dalbey. PMID:24080089

Evans, Margery L; Chapman, Matthew R

2014-08-01

333

The Circadian Clock Coordinates Ribosome Biogenesis  

PubMed Central

Biological rhythms play a fundamental role in the physiology and behavior of most living organisms. Rhythmic circadian expression of clock-controlled genes is orchestrated by a molecular clock that relies on interconnected negative feedback loops of transcription regulators. Here we show that the circadian clock exerts its function also through the regulation of mRNA translation. Namely, the circadian clock influences the temporal translation of a subset of mRNAs involved in ribosome biogenesis by controlling the transcription of translation initiation factors as well as the clock-dependent rhythmic activation of signaling pathways involved in their regulation. Moreover, the circadian oscillator directly regulates the transcription of ribosomal protein mRNAs and ribosomal RNAs. Thus the circadian clock exerts a major role in coordinating transcription and translation steps underlying ribosome biogenesis. PMID:23300384

Symul, Laura; Martin, Eva; Atger, Florian; Naef, Felix; Gachon, Frédéric

2013-01-01

334

Food-dependent exercise-induced anaphylaxis with a high level of plasma noradrenaline.  

PubMed

Ingesting certain foods sometimes triggers anaphylaxis when followed by exercise (food-dependent exercise-induced anaphylaxis, FDEIA). Specific food-induced mucocutaneous urticaria may also progress to anaphylaxis (oral allergy syndrome, OAS). A positive skin test and/or radioallergosorbent test (RAST) to the foods suggest involvement of immunoglobulin (Ig)E-anaphylaxis in both disorders. The triggering foods and initial target organs are usually different in each case. In the present study, a 32-year-old male reported dyspnea accompanied by wheals, and symptoms of low blood pressure while walking after eating Chinese noodles and donuts. He also reported uncomfortable sensations in his mouth and throat after ingesting melon. Exercise challenge tests were administered. Serum histamine, plasma adrenaline, noradrenaline and dopamine were measured pre- and post-test. No symptoms were induced by exercise or by the ingestion of any single food item before exercise. However, numerous wheals appeared when exercise followed the combined ingestion of foods. Likewise, the sequence of eating pancakes and then exercising resulted in numerous wheals and anaphylaxis. Olopatadine hydrochloride and ketotifen fumarate completely inhibited this anaphylaxis. The skin prick tests resulted in fruit-induced erythema and wheals. The results of these tests with wheat, butter and sugar were negative, and no symptoms were induced by the exercise test after ingestion of watermelon, melon or apple. The anaphylactoid symptoms were accompanied by a significant increase of plasma noradrenaline. In this case, not only wheat, but sugar and butter may induce the onset of FDEIA. There was no significant correlation between the intensity of the symptoms and the serum histamine levels in the present case. Noradrenaline may be involved in the onset of FDEIA, since noradrenaline may selectively inhibit T-helper (Th)1 functions while favoring Th2 responses. The tests showed no cross-reactivity between the causative foods of OAS and FDEIA, indicating that the mechanisms of onset are different between them. PMID:17239147

Kato, Yukihiko; Nagai, Ayako; Saito, Masuyoshi; Ito, Tomonobu; Koga, Michiyuki; Tsuboi, Ryoji

2007-02-01

335

A rat model of exercise-induced asthma: a nonspecific response to a specific immunogen  

PubMed Central

Exercise-induced bronchoconstriction (EIB) is common; however, key aspects of its pathogenesis are still unclear. We investigated the feasibility of adapting an established animal model of asthma to investigate the earliest stages of EIB. The hypothesis was that a single exposure to a normally innocuous, and brief, exercise challenge could trigger EIB symptoms in rats previously sensitized to ovalbumin (OVA) but otherwise unchallenged. Brown-Norway rats were sensitized by intraperitoneal injection of OVA at 0 and 2 wk. At week 3, animals were exposed to either aerosolized OVA (SS) or exercise (EXS). A trained, blinded, clinical observer graded EIB by respiratory sounds. Plasma and lung cytokine levels were analyzed. No control rats with or without exercise (EX, CON) showed evidence of EIB. Eighty percent of the SS group demonstrated abnormal breath sounds upon exposure to aerosolized OVA. Approximately 30% of EXS rats sensitized to OVA but exposed only to exercise had abnormal breath sounds. Lung tissue levels of TNF-?, IL-1?, growth-related oncogene/keratinocyte/chemoattractant, and IFN-? were significantly higher (P < 0.001) in the SS group, relative to all other groups. Changes in most of these cytokines were not notable in the EXS rats, suggesting a different mechanism of EIB. Remarkably, IFN-?, but not the other cytokines measured, was significantly elevated following brief exercise in both sensitized and unsensitized rats. Exercise led to detectable breathing sound abnormalities in sensitized rats, but less severe than those observed following classical OVA challenge. Precisely how this immune crossover occurs is not known, but this model may be useful in elucidating essential mechanisms of EIB. PMID:21228339

Kodesh, Einat; Zaldivar, Frank; Schwindt, Christina; Tran, Phuc; Yu, Alvin; Camilon, Marinelle; Nance, Dwight M.; Leu, Szu-Yun; Cooper, Dan

2011-01-01

336

Catalase activity prevents exercise-induced up-regulation of vasoprotective proteins in venous tissue  

PubMed Central

Abstract Physical activity induces favourable changes of arterial gene expression and protein activity, although little is known about its effect in venous tissue. Although our understanding of the initiating molecular signals is still incomplete, increased expression of endothelial nitric oxide synthase (eNOS) is considered a key event. This study sought to investigate the effects of two different training protocols on the expression of eNOS and extracellular superoxide dismutase (ecSOD) in venous and lung tissue and to evaluate the underlying molecular mechanisms. C57Bl/6 mice underwent voluntary exercise or forced physical activity. Changes of vascular mRNA and protein levels and activity of eNOS, ecSOD and catalase were determined in aorta, heart, lung and vena cava. Both training protocols similarly increased relative heart weight and resulted in up-regulation of aortic and myocardial eNOS. In striking contrast, eNOS expression in vena cava and lung remained unchanged. Likewise, exercise up-regulated ecSOD in the aorta and in left ventricular tissue but remained unchanged in lung tissue. Catalase expression in lung tissue and vena cava of exercised mice exceeded that in aorta by 6.9- and 10-fold, respectively, suggesting a lack of stimulatory effects of hydrogen peroxide. In accordance, treatment of mice with the catalase inhibitor aminotriazole for 6 weeks resulted in significant up-regulation of eNOS and ecSOD in vena cava. These data suggest that physiological venous catalase activity prevents exercise-induced up-regulation of eNOS and ecSOD. Furthermore, therapeutic inhibition of vascular catalase might improve pulmonary rehabilitation. PMID:21129156

Dao, Vu Thao-Vi; Floeren, Melanie; Kumpf, Stephanie; Both, Charlotte; Peter, Bärbel; Balz, Vera; Suvorava, Tatsiana; Kojda, Georg

2011-01-01

337

Exercise induces cortical plasticity after neonatal spinal cord injury in the rat  

PubMed Central

Exercise-induced cortical plasticity is associated with improved functional outcome after brain or nerve injury. Exercise also improves functional outcomes after spinal cord injury, but its effects on cortical plasticity are not known. The goal of this investigation was to study the effect of moderate exercise (treadmill locomotion, 3 min/day, 5days/week) on the somatotopic organization of forelimb and hindlimb somatosensory cortex (SI) after neonatal thoracic transection. We used adult rats spinalized as neonates because some of these animals develop weight-supported stepping and, therefore, the relationship between cortical plasticity and stepping could also be examined. Acute, single-neuron mapping was used to determine the percentage of cortical cells responding to cutaneous forelimb stimulation in normal, spinalized, and exercised spinalized rats. Multiple single neuron recording from arrays of chronically implanted microwires examined the magnitude of response of these cells in normal and exercised spinalized rats. Our results show that exercise not only increased the percentage of responding cells in the hindlimb SI, but also increased the magnitude of the response of these cells. This increase in response magnitude was correlated with behavioral outcome measures. In the forelimb SI, neonatal transection reduced the percentage of responding cells to forelimb stimulation but exercise reversed this loss. This restoration in the percentage of responding cells after exercise was accompanied by an increase in their response magnitude. Therefore, the increase in responsiveness of hindlimb SI to forelimb stimulation after neonatal transection and exercise may be due, in part, to the effect of exercise on the forelimb SI. PMID:19515923

Kao, T; Shumsky, JS; Murray, M; Moxon, KA

2009-01-01

338

Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth.  

PubMed

Regular physical activity protects against the development of breast and colon cancer, since it reduces the risk of developing these by 25-30%. During exercise, humoral factors are released from the working muscles for endocrinal signaling to other organs. We hypothesized that these myokines mediate some of the inhibitory effects of exercise on mammary cancer cell proliferation. Serum and muscles were collected from mice after an exercise bout. Incubation with exercise-conditioned serum inhibited MCF-7 cell proliferation by 52% and increased caspase activity by 54%. A similar increase in caspase activity was found after incubation of MCF-7 cells with conditioned media from electrically stimulated myotubes. PCR array analysis (CAPM-0838E; SABiosciences) revealed that seven genes were upregulated in the muscles after exercise, and of these oncostatin M (OSM) proved to inhibit MCF-7 proliferation by 42%, increase caspase activity by 46%, and induce apoptosis. Blocking OSM signaling with anti-OSM antibodies reduced the induction of caspase activity by 51%. To verify that OSM was a myokine, we showed that it was significantly upregulated in serum and in three muscles, tibialis cranialis, gastronemius, and soleus, after an exercise bout. In contrast, OSM expression remained unchanged in subcutaneous and visceral adipose tissue, liver, and spleen (mononuclear cells). We conclude that postexercise serum inhibits mammary cancer cell proliferation and induces apoptosis of these cells. We suggest that one or more myokines secreted from working muscles may be mediating this effect and that OSM is a possible candidate. These findings emphasize that role of physical activity in cancer treatment, showing a direct link between exercise-induced humoral factors and decreased tumor cell growth. PMID:21653222

Hojman, Pernille; Dethlefsen, Christine; Brandt, Claus; Hansen, Jakob; Pedersen, Line; Pedersen, Bente Klarlund

2011-09-01

339

Exercise-induced bronchoconstriction: The effects of montelukast, a leukotriene receptor antagonist  

PubMed Central

Exercise-induced bronchoconstriction (EIB) is very common in both patients with asthma and those who are otherwise thought to be normal. The intensity of exercise as well as the type of exercise is important in producing symptoms. This may make some types of exercise such as swimming more suitable and extended running more difficult for patients with this condition. A better understanding of EIB will allow the physician to direct the patient towards a type of exercise and medications that can result in a more active lifestyle without the same concern for resulting symptoms. This is especially important for schoolchildren who are usually enrolled in physical education classes and elite athletes who may desire to participate in competitive sports. Fortunately several medications (short- and long-acting ?2-agonists, cromolyn, nedocromil, inhaled corticosteroids, and more recently leukotriene modifiers) have been shown to be effective in preventing or attenuating the effects of exercise in many patients. In addition, inhaled ?2-agonists have been shown to quickly reverse the airway obstruction that develops in patients and continue to be the reliever medications of choice. Inhaled corticosteroids are increasingly being recommended as regular therapy now that the role of inflammation and airway injury has been identified in EIB. With the discovery that there is a release of mediators such as histamine and leukotrienes from cells in the airway following exercise with resulting airway obstruction in susceptible individuals, interest has turned to attenuating their effects with mediator antagonists especially those that block the effects of leukotrienes. Studies with an oral leukotriene antagonist, montelukast, have shown beneficial effects in adults and children aged as young as 6 years with EIB. These effects can be demonstrated as soon as two hours and as long as 24 hours after administration without a demonstrated loss of a protective effect after months of treatment. The studies leading up to and resulting in an approval of montelukast for EIB for patients aged 15 years and older are reviewed in this paper. PMID:20011246

Kemp, James P

2009-01-01

340

Exercise-Induced Wheeze, Urgent Medical Visits, and Neighborhood Asthma Prevalence  

PubMed Central

OBJECTIVE: Exercise-induced wheeze (EIW) may identify a distinct population among asthmatics and give insight into asthma morbidity etiology. The prevalence of pediatric asthma and associated urgent medical visits varies greatly by neighborhood in New York City and is highest in low-income neighborhoods. Although increased asthma severity might contribute to the disparities in urgent medical visits, when controlling for health insurance coverage, we previously observed no differences in clinical measures of severity between asthmatic children living in neighborhoods with lower (3%–9%) versus higher (11%–19%) asthma prevalence. Among these asthmatics, we hypothesized that EIW would be associated with urgent medical visits and a child’s neighborhood asthma prevalence. METHODS: Families of 7- to 8-year-old children were recruited into a case-control study of asthma through an employer-based health insurance provider. Among the asthmatics (n = 195), prevalence ratios (PRs) for EIW were estimated. Final models included children with valid measures of lung function, seroatopy, and waist circumference (n = 140). RESULTS: EIW was associated with urgent medical visits for asthma (PR, 2.29; P = .021), independent of frequent wheeze symptoms. In contrast to frequent wheeze, EIW was not associated with seroatopy or exhaled NO, suggesting a distinct mechanism. EIW prevalence among asthmatics increased with increasing neighborhood asthma prevalence (PR, 1.09; P = .012), after adjustment for race, ethnicity, maternal asthma, environmental tobacco smoke, household income, and neighborhood income. CONCLUSIONS: EIW may contribute to the disparities in urgent medical visits for asthma between high- and low-income neighborhoods. Physicians caring for asthmatics should consider EIW an indicator of risk for urgent medical visits. PMID:23248227

Mainardi, Timothy R.; Mellins, Robert B.; Miller, Rachel L.; Acosta, Luis M.; Cornell, Alexandra; Hoepner, Lori; Quinn, James W.; Yan, Beizhan; Chillrud, Steven N.; Olmedo, Omar E.; Perera, Frederica P.; Goldstein, Inge F.; Rundle, Andrew G.; Jacobson, Judith S.

2013-01-01

341

Prunus mume extract ameliorates exercise-induced fatigue in trained rats.  

PubMed

This study evaluated the effects of Prunus mume extract on exercise-induced fatigue recovery in a trained rat model. Male Sprague-Dawley rats were raised either on a control diet (EC) or on diets supplemented with 0.15% (0.15EP), 0.3% (0.3EP), or 0.9% (0.9EP) Prunus mume extract for 4 weeks (n = 18). Each dietary group was divided into two subgroups; at the end of the experimental period, one subgroup was sacrificed immediately after a 1-hour exercise, and the other subgroup was sacrificed after a 30-minute rest following the exercise (n = 9). Compared to the values for EC rats, serum ammonia concentration was significantly lower in 0.3EP and 0.9EP rats that were sacrificed immediately after the exercise-loading and in 0.15EP, 0.3EP and 0.9EP rats that were sacrificed after a 30-minute rest following the exercise. Compared to that in EC rats, serum lactate levels were significantly lower in rats fed 0.15% or higher levels of P. mume extract when they were sacrificed after a 30-minute rest following the exercise. Dietary supplementation with the P. mume extract significantly elevated hepatic and muscle glycogen concentrations of the rats sacrificed immediately after the exercise. P. mume extract significantly reduced lactate dehydrogenase activity and increased citrate synthase activity in the skeletal muscles of the rats sacrificed immediately after the exercise-loading. Taken together, these results indicate that the P. mume extract administered during endurance exercise training may enhance the oxidative capacity of exercising skeletal muscle and may induce the muscle to prefer fatty acids for its fuel use rather than amino acids or carbohydrates. PMID:18800892

Kim, Soyoung; Park, Sung-Hee; Lee, Hye-Nam; Park, Taesun

2008-09-01

342

EFFECTS OF MASSAGE ON MUSCULAR STRENGTH AND PROPRIOCEPTION AFTER EXERCISE-INDUCED MUSCLE DAMAGE.  

PubMed

Exercise-induced muscle damage (EIMD), which is commonly associated with eccentric exercise, unaccustomed exercise, and resistance training, may lead to delayed-onset muscle soreness, swelling, decreased muscle strength, and range of motion. Many researchers have evaluated various interventions to treat the signs and symptoms of EIMD. However, the effects of massage after EIMD are unclear. Here, we investigated the effect of massage on muscle strength and proprioception following EIMD. All subjects randomly were divided into a EIMD-treated control group (n = 10) and an massage-treated after EIMD experimental group (n = 11). EIMD was induced by repeated exercise. Massage treatment was provided by physiotherapist for a 15 min. It consists of light stroking, milking, friction, and skin rolling. Lactate was evaluated by lactate pro analyzer in pre and post exercise. Surface electromyography (muscle activity) and sonography (muscle thickness) were used to confirm the muscular characteristics. Proprioception was investigated by dual inclinometer. As a result, massage treatment on the gastrocnemius after EIMD increased activation of the medial gastrocnemius during contraction (p < 0.05). In the lateral and medial gastrocnemius, the ?s which is angle between muscle fibers and superficial aponeurosis showed a significant change (p < 0.05). However, there are no differences in the ?d which is angle between muscle fibers and deep aponeurosis. We also found that proprioceptive acuity in the ankle joint was significantly greater in the massage-treated experimental group compared to that in the control group (p < 0.05). These findings suggest that massage of the gastrocnemius after EIMD can improve muscle strength and proprioception by influencing the superficial layer of the gastrocnemius. PMID:25226328

Shin, Mal-Soon; Sung, Yun-Hee

2014-09-15

343

Exercise-induced bronchospasm: a pilot survey in Nairobi school children.  

PubMed

Exercise-induced bronchospasm (EIB), a common feature of asthma in children, has been used as the outcome measure in community-based surveys of childhood asthma to circumvent difficulties arising from relative lack of objectivity in the use of questionnaires in communities with different cultural and language orientations. We report here the results of the first community-based study of childhood asthma in Kenya using EIB as the outcome measurement. The data was collected in a pilot study to develop methodology for a larger subsequent study. The survey targeted grade four children in five Nairobi City Council school each representing a neighbourhood social economic status (SES). Out of 597 eligible, 408 children took part in the study (68% participation rate). EIB defined as decline in FEV1 of 15% or more, post-exercise was found in 10.5% (95% CI; 10.3, 10.7) of the children studied, the highest rate reported so far in Africa. While boys were more likely to exhibit EIB compared to girls, the prevalence of EIB tended to decrease with age, especially among children residing in low SES neighbourhoods where the EIB prevalence rates tended to be lower compared to those among children from higher SES neighbourhoods. However, none of these differences was statistically significant. This study confirms the feasibility of undertaking exercise challenge tests in the African context and we recommend that additional studies of similar nature be carried out in other populations of Africa to explore the potential of using an exercise test as a marker of asthma in epidemiologic studies. PMID:9557438

Ng'ang'a, L W; Odhiambo, J A; Omwega, M J; Gicheha, C M; Becklake, M R; Menzies, R; Mohammed, N; Macklem, P T

1997-11-01

344

Resistance exercise-induced fluid shifts: change in active muscle size and plasma volume  

NASA Technical Reports Server (NTRS)

The purpose of this study was to test the hypothesis that the reduction in plasma volume (PV) induced by resistance exercise reflects fluid loss to the extravascular space and subsequently selective increase in cross-sectional area (CSA) of active but not inactive skeletal muscle. We compared changes in active and inactive muscle CSA and PV after barbell squat exercise. Magnetic resonance imaging (MRI) was used to quantify muscle involvement in exercise and to determine CSA of muscle groups or individual muscles [vasti (VS), adductor (Add), hamstring (Ham), and rectus femoris (RF)]. Muscle involvement in exercise was determined using exercise-induced contrast shift in spin-spin relaxation time (T2)-weighted MR images immediately postexercise. Alterations in muscle size were based on the mean CSA of individual slices. Hematocrit, hemoglobin, and Evans blue dye were used to estimate changes in PV. Muscle CSA and PV data were obtained preexercise and immediately postexercise and 15 and 45 min thereafter. A hierarchy of muscle involvement in exercise was found such that VS > Add > Ham > RF, with the Ham and RF showing essentially no involvement. CSA of the VS and Add muscle groups were increased 10 and 5%, respectively, immediately after exercise in each thigh with no changes in Ham and RF CSA. PV was decreased 22% immediately following exercise. The absolute loss of PV was correlated (r2 = 0.75) with absolute increase in muscle CSA immediately postexercise, supporting the notion that increased muscle size after resistance exercise reflects primarily fluid movement from the vascular space into active but not inactive muscle.

Ploutz-Snyder, L. L.; Convertino, V. A.; Dudley, G. A.

1995-01-01

345

Ascaris, atopy, and exercise-induced bronchoconstriction in rural and urban South African children  

PubMed Central

Background Populations with endemic parasitosis have high levels of IgE but low levels of allergic disease. We investigated the association between infection with the parasite Ascaris allergic sensitization, and exercise-induced bronchospasm (EIB). Objective We sought to investigate the effect of Ascaris infection on bronchial hyperreactivity, skin testing, and specific IgE levels. Methods A cross-sectional prevalence survey was conducted in urban and rural South African children to measure levels of EIB. A sample of children was enrolled in a nested case-control study for further investigation based on response to exercise. Analyses used weighted logistic regression. Results Geometric mean total IgE levels were higher in Ascaris–infected subjects (infected subjects: 451 IU (95% CI, 356-572) vs uninfected subjects: 344 IU (95% CI, 271-437), P 5.04), and high levels of total IgE were positively associated with detection of specific IgE to the aeroallergens tested, but there was no significant association between Ascaris infection and titers of specific IgE. Ascaris infection was associated with a decreased risk of a positive skin test response (odds ratio, 0.63; 95% CI, 0.42–0.94; P 5 .03) but an increased risk of EIB (odds ratio, 1.62; 95% CI, 1.23-2.11; P 5 .001). Conclusion In areas of high parasite endemicity, Ascaris might induce an inflammatory response in the lungs independent of its effect on IgE production. This could explain some of the contradictory findings seen in studies examining the association between geohelminth infection, atopy, and asthma. PMID:19962746

Calvert, James; Burney, Peter

2015-01-01

346

Is lactic acidosis a cause of exercise induced hyperventilation at the respiratory compensation point?  

PubMed Central

Objectives: The respiratory compensation point (RCP) marks the onset of hyperventilation ("respiratory compensation") during incremental exercise. Its physiological meaning has not yet been definitely determined, but the most common explanation is a failure of the body's buffering mechanisms which leads to metabolic (lactic) acidosis. It was intended to test this experimentally. Methods: During a first ramp-like exercise test on a cycle ergometer, RCP (range: 2.51–3.73 l*min–1 oxygen uptake) was determined from gas exchange measurements in five healthy subjects (age 26–42; body mass index (BMI) 20.7–23.9 kg*m–2; VO2peak 51.3–62.1 ml*min–1*kg–1). On the basis of simultaneous determinations of blood pH and base excess, the necessary amount of bicarbonate to completely buffer the metabolic acidosis was calculated. This quantity was administered intravenously in small doses during a second, otherwise identical, exercise test. Results: In each subject sufficient compensation for the acidosis, that is, a pH value constantly above 7.37, was attained during the second test. A delay but no disappearance of the hyperventilation was present in all participants when compared with the first test. RCP occurred on average at a significantly (p = 0.043) higher oxygen uptake (+0.15 l*min–1) compared with the first test. Conclusions: For the first time it was directly demonstrated that exercise induced lactic acidosis is causally involved in the hyperventilation which starts at RCP. However, it does not represent the only additional stimulus of ventilation during intense exercise. Muscle afferents and other sensory inputs from exercising muscles are alternative triggering mechanisms. PMID:15388552

Meyer, T; Faude, O; Scharhag, J; Urhausen, A; Kindermann, W

2004-01-01

347

Regional pulmonary veno-occlusion: a newly identified lesion of equine exercise-induced pulmonary hemorrhage.  

PubMed

Exercise-induced pulmonary hemorrhage (EIPH) is common in horses following intense exertion, occurring in up to 75% of racing Thoroughbreds and Standardbreds. In spite of this, the pathogenesis of EIPH is poorly understood. In 7 racing Thoroughbred horses with EIPH, 6 sections were collected from the left and right lung, representing the cranial, middle, and caudal region of the dorsal and ventral lung (84 sites total). Grossly, both right and left lungs had numerous dark brown to blue-black foci along the caudodorsal visceral pleura. Tissue sections were stained with hematoxylin-eosin, Masson's trichrome, and Prussian blue. Verhoeff Van Gieson and immunohistochemistry for alpha-smooth muscle actin were used to assess the pulmonary vasculature. Histologic scores (HS = 0-3) were assigned to each region/slide for the presence and severity of 5 findings: interstitial fibrosis, hemosiderin accumulation, pleural/interlobular septal thickness, arterial and venous wall thickness, and evidence of angiogenesis (maximum cumulative HS = 15). Thirty-nine of the 84 (46%) sections were histologically normal (HS = 0); 33/84 (39%) were mildly to moderately affected, with small amounts of hemosiderin and fibrosis (HS = 1-9) while 12/84 (14%), primarily from the dorsocaudal lung, had severe vascular remodeling, fibrosis, and hemosiderin accumulation (HS = 10-15). In the latter, veno-occlusive remodeling of the intralobular veins colocalized with hemosiderosis, fibrosis, hypertrophy of vessels within the pleura, and interlobular septa and bronchial neovascularization. We propose that regional veno-occlusive remodeling, especially within the caudodorsal lung fields, contributes to the pathogenesis of EIPH, with the venous remodeling leading to regional vascular congestion and hemorrhage, hemosiderin accumulation, fibrosis, and bronchial angiogenesis. PMID:18487488

Williams, K J; Derksen, F J; de Feijter-Rupp, H; Pannirselvam, R R; Steel, C M; Robinson, N E

2008-05-01

348

Microarray analyses reveal novel targets of exercise-induced stress resistance in the dorsal raphe nucleus  

PubMed Central

Serotonin (5-HT) is implicated in the development of stress-related mood disorders in humans. Physical activity reduces the risk of developing stress-related mood disorders, such as depression and anxiety. In rats, 6 weeks of wheel running protects against stress-induced behaviors thought to resemble symptoms of human anxiety and depression. The mechanisms by which exercise confers protection against stress-induced behaviors, however, remain unknown. One way by which exercise could generate stress resistance is by producing plastic changes in gene expression in the dorsal raphe nucleus (DRN). The DRN has a high concentration of 5-HT neurons and is implicated in stress-related mood disorders. The goal of the current experiment was to identify changes in the expression of genes that could be novel targets of exercise-induced stress resistance in the DRN. Adult, male F344 rats were allowed voluntary access to running wheels for 6 weeks; exposed to inescapable stress or no stress; and sacrificed immediately and 2 h after stressor termination. Laser capture micro dissection selectively sampled the DRN. mRNA expression was measured using the whole genome Affymetrix microarray. Comprehensive data analyses of gene expression included differential gene expression, log fold change (LFC) contrast analyses with False Discovery Rate correction, KEGG and Wiki Web Gestalt pathway enrichment analyses, and Weighted Gene Correlational Network Analysis (WGCNA). Our results suggest that physically active rats exposed to stress modulate expression of twice the number of genes, and display a more rapid and strongly coordinated response, than sedentary rats. Bioinformatics analyses revealed several potential targets of stress resistance including genes that are related to immune processes, tryptophan metabolism, and circadian/diurnal rhythms. PMID:23717271

Loughridge, Alice B.; Greenwood, Benjamin N.; Day, Heidi E. W.; McQueen, Matthew B.; Fleshner, Monika

2013-01-01

349

What Makes a Difference in Exercise-Induced Bronchoconstriction: An 8 Year Retrospective Analysis  

PubMed Central

Background Exercise-induced bronchoconstriction (EIB) was recently classified into EIB alone and EIB with asthma, based on the presence of concurrent asthma. Objective Differences between EIB alone and EIB with asthma have not been fully described. Methods We retrospectively reviewed who visited an allergy clinic for respiratory symptoms after exercise and underwent exercise bronchial provocation testing. More than a 15% decrease of forced expiratory volume in 1 second (FEV1) from baseline to the end of a 6 min free-running challenge test was interpreted as positive EIB. Results EIB was observed in 66.9% of the study subjects (89/133). EIB-positive subjects showed higher positivity to methacholine provocation testing (61.4% vs. 18.9%, p<0.001) compared with EIB-negative subjects. In addition, sputum eosinophilia was more frequently observed in EIB-positive subjects than in EIB-negative subjects (56% vs. 23.5%, p?=?0.037). The temperature and relative humidity on exercise test day were significantly related with the EIB-positive rate. Positive EIB status was correlated with both temperature (p?=?0.001) and relative humidity (p?=?0.038) in the methacholine-negative EIB group while such a correlation was not observed in the methacholine-positive EIB group. In the methacholine-positive EIB group the time to reach a 15% decrease in FEV1 during exercise was significantly shorter than that in the methacholine-negative EIB group (3.2±0.7 min vs. 8.6±1.6 min, p?=?0.004). Conclusions EIB alone may be a distinct clinical entity from EIB with asthma. Conditions such as temperature and humidity should be considered when performing exercise tests, especially in subjects with EIB alone. PMID:24498034

Park, Han-Ki; Jung, Jae-Woo; Cho, Sang-Heon; Min, Kyung-Up; Kang, Hye-Ryun

2014-01-01

350

Effects of Exercise Induced Low Back Pain on Intrinsic Trunk Stiffness and Paraspinal Muscle Reflexes  

PubMed Central

The purpose of this study was to 1) compare trunk neuromuscular behavior between individuals with no history of low back pain (LBP) and individuals who experience exercise-induced LBP (eiLBP) when pain free, and 2) investigate changes in trunk neuromuscular behavior with eiLBP. Seventeen young adult males participated including eight reporting recurrent, acute eiLBP and nine control participants reporting no history of LBP. Intrinsic trunk stiffness and paraspinal muscle reflex delay were determined in both groups using sudden trunk flexion position perturbations 1-2 days following exercise when the eiLBP participants were experiencing an episode of LBP (termed post-exercise) and 4-5 days following exercise when eiLBP had subsided (termed post-recovery). Post-recovery, when the eiLBP group was experiencing minimal LBP, trunk stiffness was 26% higher in the eiLBP group compared to the control group (p=0.033) and reflex delay was not different (p=0.969) between groups. Trunk stiffness did not change (p=0.826) within the eiLBP group from post-exercise to post-recovery, but decreased 22% within the control group (p=0.002). Reflex delay decreased 11% within the eiLBP group from post-exercise to post-recovery (p=0.013), and increased 15% within the control group (p=0.006). Although the neuromuscular mechanisms associated with eiLBP and chronic LBP may differ, these results suggest that previously-reported differences in trunk neuromuscular behavior between individuals with chronic LBP and healthy controls reflect a combination of inherent differences in neuromuscular behavior between these individuals as well as changes in neuromuscular behavior elicited by pain. PMID:23182221

Miller, Emily M.; Bazrgari, Babak; Nussbaum, Maury A.; Madigan, Michael L.

2012-01-01

351

Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.  

PubMed

This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

2014-01-01

352

Enantiomeric Natural Products: Occurrence and Biogenesis**  

PubMed Central

In Nature, chiral natural products are usually produced in optically pure form; however, on occasion Nature is known to produce enantiomerically opposite metabolites. These enantiomeric natural products can arise in Nature from a single species, or from different genera and/or species. Extensive research has been carried out over the years in an attempt to understand the biogenesis of naturally occurring enantiomers, however, many fascinating puzzles and stereochemical anomalies still remain. PMID:22555867

Finefield, Jennifer M.; Sherman, David H.; Kreitman, Martin; Williams, Robert M.

2012-01-01

353

Efficiency and specificity in micro RNA biogenesis  

PubMed Central

Primary microRNA cleavage by the Drosha–Dgcr8 ‘Microprocessor’ complex is critical for microRNA biogenesis. Yet, the Microprocessor may also cleave other nuclear RNAs in a nonspecific manner. We studied Microprocessor function using mathematical modeling and experiments in mouse and human tissues. We found that the autoregulatory feedback on Microprocessor expression is instrumental for balancing the efficiency and specificity of its activity by effectively tuning Microprocessor levels to those of its pri-miRNA substrate. PMID:22580560

Barad, Omer; Mann, Mati; Chapnik, Elik; Shenoy, Archana; Blelloch, Robert; Barkai, Naama; Hornstein, Eran

2015-01-01

354

Anatomy, biogenesis and regeneration of salivary glands.  

PubMed

An overview of the anatomy and biogenesis of salivary glands is important in order to understand the physiology, functions and disorders associated with saliva. A major disorder of salivary glands is salivary hypofunction and resulting xerostomia, or dry mouth, which affects hundreds of thousands of patients each year who suffer from salivary gland diseases or undergo head and neck cancer treatment. There is currently no curative therapy for these patients. To improve these patients' quality of life, new therapies are being developed based on findings in salivary gland cell and developmental biology. Here we discuss the anatomy and biogenesis of the major human salivary glands and the rodent submandibular gland, which has been used extensively as a research model. We also include a review of recent research on the identification and function of stem cells in salivary glands, and the emerging field of research suggesting that nerves play an instructive role during development and may be essential for adult gland repair and regeneration. Understanding the molecular mechanisms involved in gland biogenesis provides a template for regenerating, repairing or reengineering diseased or damaged adult human salivary glands. We provide an overview of 3 general approaches currently being developed to regenerate damaged salivary tissue, including gene therapy, stem cell-based therapy and tissue engineering. In the future, it may be that a combination of all three will be used to repair, regenerate and reengineer functional salivary glands in patients to increase the secretion of their saliva, the focus of this monograph. PMID:24862590

Holmberg, Kyle V; Hoffman, Matthew P

2014-01-01

355

Regulation of Skeletal Muscle Mitochondrial Function: Genes to Proteins  

PubMed Central

The impact of aging on mitochondrial function and the deterministic role of mitochondria on scenescence continue to be topics of vigorous debate. Many studies report that skeletal muscle mitochondrial content and function are reduced with aging and metabolic diseases associated with insulin resistance. However, an accumulating body of literature suggests that physical inactivity typical of aging may be a more important determinant of mitochondrial function than chronological age, per se. Reports of age-related declines in mitochondrial function have spawned a vast body of literature devoted to understanding the underlying mechanisms. These mechanisms include decreased abundance of mtDNA, reduced mRNA levels, as well as decreased synthesis and expression of mitochondrial proteins, ultimately resulting in decreased function of the whole organelle. Effective therapies to prevent reverse, or delay the onset of the aformentioned mitochondrial changes, regardless of their inevitability or precise underlying causes, require an intimate understanding of the processes that regulate mitochondrial biogenesis, which necessitates the coordinated regulation of nuclear and mitochondrial genomes. Herein we review the current thinking on regulation of mitochondrial biogenesis by transcription factors and transcriptional co-activators and the role of hormones and exercise in initiating this process. We review how exercise may help preserve mitochondrial content and functionality across the lifespan, and how physical inactivity is emerging as a major determinant of many age-associated changes at the level of the mitochondrion. We also review evidence that some mitochondrial changes with aging are independent of exercise or physical activity and appear to be inevitable consequences of old age. PMID:20345409

Lanza, Ian R.; Nair, K. Sreekumaran

2011-01-01

356

Caenorhabditis elegans neuron degeneration and mitochondrial suppression caused by selected environmental chemicals  

PubMed Central

Mitochondrial alterations have been documented for many years in the brains of Parkinson’s disease (PD), a disorder that is characterized by the selective loss of dopamine neurons. Recent studies have demonstrated that Parkinson’s disease-associated proteins are either present in mitochondria or translocated into mitochondria in response to stress, further reinforcing the importance of the mitochondrial function in the pathogenesis of Parkinson’s disease. Exposure to environmental chemicals such as pesticides and heavy metals has been suggested as risk factors in the development of Parkinson’s disease. It has been reported that a number of environmental agents including tobacco smoke and perfluorinated compounds, pesticides, as well as metals (Mn2+ and Pb2+) modulate mitochondrial function. However the exact mechanism of mitochondrial alteration has not been defined in the context of the development and progression of Parkinson’s disease. The complexity of the mammalian system has made it difficult to dissect the molecular components involved in the pathogenesis of Parkinson’s disease. In the present study we used the nematode Caenorhabditis elegans (C. elegans) model of neuron degeneration and investigated the effect of environmental chemicals on mitochondrial biogenesis and mitochondrial gene regulation. Chronic exposure to low concentration (2 or 4 ?M) of pesticide rotenone, resulted in significant loss of dopamine neuron in C. elegans, a classic feature of Parkinson’s disease. We then determined if the rotenone-induced neuron degeneration is accompanied by a change in mitochondria biogenesis. Analysis of mitochondrial genomic replication by quantitative PCR showed a dramatic decrease in mitochondrial DNA (mtDNA) copies of rotenone-treated C. elegans compared to control. This decreased mitochondrial biogenesis occurred prior to the development of loss of dopamine neurons, and was persistent. The inhibition of mtDNA replication was also found in C. elegans exposed to another neuron toxicant Mn2+ at the concentration 50 or 100 mM. We further examined the mitochondrial gene expression and found significant lower level of mitochondrial complex IV subunits COI and COII in C. elegans exposed to rotenone. These results demonstrate that environmental chemicals cause persistent suppression of mitochondrial biogenesis and mitochondrial gene expression, and suggest a critical role of modifying mitochondrial biogenesis in toxicants-induced neuron degeneration in C. elegans model. PMID:24380023

Zhou, Shaoyu; Wang, Zemin; Klaunig, James E

2013-01-01

357

Loss of mitochondrial exo/endonuclease EXOG affects mitochondrial respiration and induces ROS-mediated cardiomyocyte hypertrophy.  

PubMed

Recently, a locus at the mitochondrial exo/endonuclease EXOG gene, which has been implicated in mitochondrial DNA repair, was associated with cardiac function. The function of EXOG in cardiomyocytes is still elusive. Here we investigated the role of EXOG in mitochondrial function and hypertrophy in cardiomyocytes. Depletion of EXOG in primary neonatal rat ventricular cardiomyocytes (NRVCs) induced a marked increase in cardiomyocyte hypertrophy. Depletion of EXOG, however, did not result in loss of mitochondrial DNA integrity. Although EXOG depletion did not induce fetal gene expression and common hypertrophy pathways were not activated, a clear increase in ribosomal S6 phosphorylation was observed, which readily explains increased protein synthesis. With the use of a Seahorse flux analyzer, it was shown that the mitochondrial oxidative consumption rate (OCR) was increased 2.4-fold in EXOG-depleted NRVCs. Moreover, ATP-linked OCR was 5.2-fold higher. This increase was not explained by mitochondrial biogenesis or alterations in mitochondrial membrane potential. Western blotting confirmed normal levels of the oxidative phosphorylation (OXPHOS) complexes. The increased OCR was accompanied by a 5.4-fold increase in mitochondrial ROS levels. These increased ROS levels could be normalized with specific mitochondrial ROS scavengers (MitoTEMPO, mnSOD). Remarkably, scavenging of excess ROS strongly attenuated the hypertrophic response. In conclusion, loss of EXOG affects normal mitochondrial function resulting in increased mitochondrial respiration, excess ROS production, and cardiomyocyte hypertrophy. PMID:25377088

Tigchelaar, Wardit; Yu, Hongjuan; de Jong, Anne Margreet; van Gilst, Wiek H; van der Harst, Pim; Westenbrink, B Daan; de Boer, Rudolf A; Silljé, Herman H W

2015-01-15

358

The Pathophysiology of Mitochondrial Biogenesis: Towards Four Decades of Mitochondrial DNA Research  

Microsoft Academic Search

Mitochondria are with very few exceptions ubiquitous organelles in eukaryotic cells where they are essential for cell life and death. Mitochondria play a central role not only in a variety of metabolic pathways including the supply of the bulk of cellular ATP through oxidative phosphorylation (OXPHOS), but also in complex processes such as development, apoptosis, and aging. Mitochondria contain their

Miguel Angel Fernández-Moreno; Belén Bornstein; Nathalie Petit; Rafael Garesse

2000-01-01

359

Erythropoietin Activates Mitochondrial Biogenesis and Couples Red Cell Mass to Mitochondrial Mass in the Heart  

EPA Science Inventory

RATIONALE: Erythropoietin (EPO) is often administered to cardiac patients with anemia, particularly from chronic kidney disease, and stimulation of erythropoiesis may stabilize left ventricular and renal function by recruiting protective effects beyond the correction of anemia. O...

360

Abnormal Synaptic Vesicle Biogenesis in Drosophila Synaptogyrin Mutants  

E-print Network

Sustained neuronal communication relies on the coordinated activity of multiple proteins that regulate synaptic vesicle biogenesis and cycling within the presynaptic terminal. Synaptogyrin and synaptophysin are conserved ...

Stevens, Robin Jean

361

Mitochondrial protein quality control in health and disease  

PubMed Central

Progressive mitochondrial dysfunction is linked with the onset of many age-related pathologies and neurological disorders. Mitochondrial damage can come in many forms and be induced by a variety of cellular insults. To preserve organelle function during biogenesis or times of stress, multiple surveillance systems work to ensure the persistence of a functional mitochondrial network. This review provides an overview of these processes, which collectively contribute to the maintenance of a healthy mitochondrial population, which is critical for cell physiology and survival. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24117041

Baker, Michael J; Palmer, Catherine S; Stojanovski, Diana

2014-01-01

362

Development of pharmacological strategies for mitochondrial disorders  

PubMed Central

Mitochondrial diseases are an unusually genetically and phenotypically heterogeneous group of disorders, which are extremely challenging to treat. Currently, apart from supportive therapy, there are no effective treatments for the vast majority of mitochondrial diseases. Huge scientific effort, however, is being put into understanding the mechanisms underlying mitochondrial disease pathology and developing potential treatments. To date, a variety of treatments have been evaluated by randomized clinical trials, but unfortunately, none of these has delivered breakthrough results. Increased understanding of mitochondrial pathways and the development of many animal models, some of which are accurate phenocopies of human diseases, are facilitating the discovery and evaluation of novel prospective treatments. Targeting reactive oxygen species has been a treatment of interest for many years; however, only in recent years has it been possible to direct antioxidant delivery specifically into the mitochondria. Increasing mitochondrial biogenesis, whether by pharmacological approaches, dietary manipulation or exercise therapy, is also currently an active area of research. Modulating mitochondrial dynamics and mitophagy and the mitochondrial membrane lipid milieu have also emerged as possible treatment strategies. Recent technological advances in gene therapy, including allotopic and transkingdom gene expression and mitochondrially targeted transcription activator-like nucleases, have led to promising results in cell and animal models of mitochondrial diseases, but most of these techniques are still far from clinical application. Linked Articles This article is part of a themed issue on Mitochondrial Pharmacology: Energy, Injury & Beyond. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2014.171.issue-8 PMID:24116962

Kanabus, M; Heales, S J; Rahman, S

2014-01-01

363

The cAMP phosphodiesterase Prune localizes to the mitochondrial matrix and promotes mtDNA replication by stabilizing TFAM.  

PubMed

Compartmentalized cAMP signaling regulates mitochondrial dynamics, morphology, and oxidative phosphorylation. However, regulators of the mitochondrial cAMP pathway, and its broad impact on organelle function, remain to be explored. Here, we report that Drosophila Prune is a cyclic nucleotide phosphodiesterase that localizes to the mitochondrial matrix. Knocking down prune in cultured cells reduces mitochondrial transcription factor A (TFAM) and mitochondrial DNA (mtDNA) levels. Our data suggest that Prune stabilizes TFAM and promotes mitochondrial DNA (mtDNA) replication through downregulation of mitochondrial cAMP signaling. In addition, our work demonstrates the prevalence of mitochondrial cAMP signaling in metazoan and its new role in mitochondrial biogenesis. PMID:25648146

Zhang, Fan; Qi, Yun; Zhou, Kiet; Zhang, Guofeng; Linask, Kaari; Xu, Hong

2015-04-01

364

Exercise-induced arterial hypoxaemia and the mechanics of breathing in healthy young women  

PubMed Central

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension () during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n= 30; maximal oxygen consumption () = 49 ± 1, range 28–62 ml kg?1 min?1) completed a stepwise treadmill test and a subset (n= 18 with EIAH) completed a constant load test (?85%) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation (), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r=–0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg?1 min?1), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min?1), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism. PMID:23587886

Dominelli, Paolo B; Foster, Glen E; Dominelli, Giulio S; Henderson, William R; Koehle, Michael S; McKenzie, Donald C; Sheel, A William

2013-01-01

365

Exercise-induced arterial hypoxaemia and the mechanics of breathing in healthy young women.  

PubMed

The purpose of this study was to characterize exercise-induced arterial hypoxaemia (EIAH), pulmonary gas exchange and respiratory mechanics during exercise, in young healthy women. We defined EIAH as a >10 mmHg decrease in arterial oxygen tension ( ) during exercise compared to rest. We used a heliox inspirate to test the hypothesis that mechanical constraints contribute to EIAH. Subjects with a spectrum of aerobic capacities (n = 30; maximal oxygen consumption ( ) = 49 ± 1, range 28-62 ml kg(-1) min(-1)) completed a stepwise treadmill test and a subset (n = 18 with EIAH) completed a constant load test (~85% ) with heliox gas. Throughout exercise arterial blood gases, oxyhaemoglobin saturation ( ), the work of breathing (WOB) and expiratory flow limitation (EFL) were assessed. Twenty of the 30 women developed EIAH with a nadir and ranging from 58 to 88 mmHg and 87 to 96%, respectively. At maximal exercise, was inversely related to (r = -0.57, P < 0.05) with notable exceptions where some subjects with low aerobic fitness levels demonstrated EIAH. Subjects with EIAH had a greater (51 ± 1 vs. 43 ± 2 ml kg(-1) min(-1)), lower end-exercise (93.2 ± 0.5 vs. 96.1 ± 0.3%) and a greater maximal energetic WOB (324 ± 19 vs. 247 ± 23 J min(-1)), but had similar resting pulmonary function compared to those without EIAH. Most subjects developed EIAH at submaximal exercise intensities, with distinct patterns of hypoxaemia. In some subjects with varying aerobic fitness levels, mechanical ventilatory constraints (i.e. EFL) were the primary mechanism associated with the hypoxaemia during the maximal test. Mechanical ventilatory constraints also prevented adequate compensatory alveolar hyperventilation in most EIAH subjects. Minimizing mechanical ventilatory constraints with heliox inspiration partially reversed EIAH in subjects who developed EFL. In conclusion, healthy women of all aerobic fitness levels can develop EIAH and begin to do so at submaximal intensities. Mechanical ventilatory constraints are a primary mechanism for EIAH in some healthy women and prevent reversal of hypoxaemia in women for whom it is not the primary mechanism. PMID:23587886

Dominelli, Paolo B; Foster, Glen E; Dominelli, Giulio S; Henderson, William R; Koehle, Michael S; McKenzie, Donald C; Sheel, A William

2013-06-15

366

p21{sup WAF1/CIP1} deficiency induces mitochondrial dysfunction in HCT116 colon cancer cells  

SciTech Connect

Highlights: Black-Right-Pointing-Pointer p21{sup -/-} HCT116 cells exhibited an increase in mitochondrial mass. Black-Right-Pointing-Pointer The expression levels of PGC-1{alpha} and AMPK were upregulated in p21{sup -/-} HCT116 cells. Black-Right-Pointing-Pointer The proliferation of p21{sup -/-} HCT116 cells in galactose medium was significantly impaired. Black-Right-Pointing-Pointer p21 may play a role in maintaining proper mitochondrial mass and respiratory function. -- Abstract: p21{sup WAF1/CIP1} is a critical regulator of cell cycle progression. However, the role of p21 in mitochondrial function remains poorly understood. In this study, we examined the effect of p21 deficiency on mitochondrial function in HCT116 human colon cancer cells. We found that there was a significant increase in the mitochondrial mass of p21{sup -/-} HCT116 cells, as measured by 10-N-nonyl-acridine orange staining, as well as an increase in the mitochondrial DNA content. In contrast, p53{sup -/-} cells had a mitochondrial mass comparable to that of wild-type HCT116 cells. In addition, the expression levels of the mitochondrial biogenesis regulators PGC-1{alpha} and TFAM and AMPK activity were also elevated in p21{sup -/-} cells, indicating that p21 deficiency induces the rate of mitochondrial biogenesis through the AMPK-PGC-1{alpha} axis. However, the increase in mitochondrial biogenesis in p21{sup -/-} cells did not accompany an increase in the cellular steady-state level of ATP. Furthermore, p21{sup -/-} cells exhibited significant proliferation impairment in galactose medium, suggesting that p21 deficiency induces a defect in the mitochondrial respiratory chain in HCT116 cells. Taken together, our results suggest that the loss of p21 results in an aberrant increase in the mitochondrial mass and in mitochondrial dysfunction in HCT116 cells, indicating that p21 is required to maintain proper mitochondrial mass and respiratory function.

Kim, Ae Jeong; Jee, Hye Jin; Song, Naree; Kim, Minjee [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of); Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of); Jeong, Seon-Young [Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of); Department of Medical Genetics, Ajou University School of Medicine (Korea, Republic of); Yun, Jeanho, E-mail: yunj@dau.ac.kr [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of) [Department of Biochemistry, College of Medicine, Dong-A University, Busan (Korea, Republic of); Mitochondria Hub Regulation Center, College of Medicine, Dong-A University, Busan (Korea, Republic of)

2013-01-11

367

Mitochondrial Cardiomyopathy  

PubMed Central

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory chain, in the absence of concomitant coronary artery disease, hypertension, valvular disease, or congenital heart disease. The typical cardiac manifestations of mitochondrial disease—hypertrophic and dilated cardiomyopathy, arrhythmias, left ventricular myocardial noncompaction, and heart failure—can worsen acutely during a metabolic crisis. The optimal management of mitochondrial disease necessitates the involvement of a multidisciplinary team, careful evaluations of patients, and the anticipation of iatrogenic and noniatrogenic complications. In this review, we describe the complex pathophysiology of mitochondrial disease and its clinical features. We focus on current practice in the diagnosis and treatment of patients with mitochondrial cardiomyopathy, including optimal therapeutic management and long-term monitoring. We hope that this information will serve as a guide for practicing cardiologists who treat patients thus affected. PMID:24082366

Meyers, Deborah E.; Basha, Haseeb Ilias; Koenig, Mary Kay

2013-01-01

368

Effects of allicin supplementation on plasma markers of exercise-induced muscle damage, IL6 and antioxidant capacity  

Microsoft Academic Search

To investigate the effects of allicin supplementation on exercise-induced muscle damage (EIMD), interleukin-6 (IL-6), and\\u000a antioxidative capacity, a double-blinded, placebo-controlled study was conducted in well-trained athletes. Subjects were randomly\\u000a assigned to an allicin supplementation group (AS group) and a control group, and received either allicin or placebo for 14 days\\u000a before and 2 days after a downhill treadmill run. Plasma creatine kinase

Quan-Sheng Su; Ye Tian; Jian-Guo Zhang; Hui Zhang

2008-01-01

369

Wnt signaling regulates mitochondrial physiology and insulin sensitivity  

PubMed Central

Mitochondria serve a critical role in physiology and disease. The genetic basis of mitochondrial regulation in mammalian cells has not yet been detailed. We performed a large-scale RNAi screen to systematically identify genes that affect mitochondrial abundance and function. This screen revealed previously unrecognized roles for >150 proteins in mitochondrial regulation. We report that increased Wnt signals are a potent activator of mitochondrial biogenesis and reactive oxygen species (ROS) generation, leading to DNA damage and acceleration of cellular senescence in primary cells. The signaling protein insulin receptor substrate-1 (IRS-1), shown here to be a transcriptional target of Wnt, is induced in this setting. The increased level of IRS-1 drives activation of mitochondrial biogenesis; furthermore, in insulin-responsive cell types, it enhances insulin signaling, raising the possibility that Wnt proteins may be used to modulate glucose homeostasis. Our results identify a key component of the mitochondrial regulatory apparatus with a potentially important link to metabolic and degenerative disorders. PMID:20634317

Yoon, John C.; Ng, Aylwin; Kim, Brian H.; Bianco, Antonio; Xavier, Ramnik J.; Elledge, Stephen J.

2010-01-01

370

Mitochondrial protein turnover: methods to measure turnover rates on a large scale.  

PubMed

Mitochondrial proteins carry out diverse cellular functions including ATP synthesis, ion homeostasis, cell death signaling, and fatty acid metabolism and biogenesis. Compromised mitochondrial quality control is implicated in various human disorders including cardiac diseases. Recently it has emerged that mitochondrial protein turnover can serve as an informative cellular parameter to characterize mitochondrial quality and uncover disease mechanisms. The turnover rate of a mitochondrial protein reflects its homeostasis and dynamics under the quality control systems acting on mitochondria at a particular cell state. This review article summarizes some recent advances and outstanding challenges for measuring the turnover rates of mitochondrial proteins in health and disease. This article is part of a Special Issue entitled "Mitochondria: From Basic Mitochondrial Biology to Cardiovascular Disease". PMID:25451168

Chan, X'avia C Y; Black, Caitlin M; Lin, Amanda J; Ping, Peipei; Lau, Edward

2015-01-01

371

Clinical significance of exercise-induced left ventricular wall motion abnormality occurring at a low heart rate  

SciTech Connect

We studied the relationship between the heart rate at the time of onset of exercise-induced wall motion abnormality and the severity of coronary artery disease in 89 patients who underwent exercise equilibrium radionuclide ventriculography as part of their evaluation for coronary artery disease. Segmental wall motion was scored with a five-point system (3 = normal; -1 = dyskinesis); a decrease of one score defined the onset of wall motion abnormality. The onset of wall motion abnormality at less than or equal to 70% of maximal predicted heart rate had 100% predictive accuracy for coronary artery disease and higher sensitivity than the onset of ischemic ST segment depression at similar heart rate during exercise: 36% (25 of 69 patients with coronary disease) vs 19% (13 of 69 patients), p = 0.01. Wall motion abnormality occurring at less than or equal to 70% of maximal predicted heart rate was present in 49% of patients (23 of 47) with critical stenosis (greater than or equal to 90% luminal diameter narrowing), and in only 5% of patients (2 of 42) without such severe stenosis, p less than 0.001. The sensitivity of exercise-induced wall motion abnormality occurring at a low heart rate for the presence of severe coronary artery disease was similar to that of a deterioration in wall motion by more than two scores during exercise (49% vs 53%) or an absolute decrease of greater than or equal to 5% in exercise left ventricular ejection fraction (49% vs 45%).

Kimchi, A.; Rozanski, A.; Fletcher, C.; Maddahi, J.; Swan, H.J.; Berman, D.S.

1987-10-01

372

Endurance exercise induces REDD1 expression and transiently decreases mTORC1 signaling in rat skeletal muscle  

PubMed Central

Abstract Working muscle conserves adenosine triphosphate (ATP) for muscle contraction by attenuating protein synthesis through several different pathways. Regulated in development and DNA damage response 1 (REDD1) is one candidate protein that can itself attenuate muscle protein synthesis during muscle contraction. In this study, we investigated whether endurance exercise induces REDD1 expression in association with decreased mammalian target of rapamycin (mTOR) complex I (mTORC1) signaling and global protein synthesis in rat skeletal muscle. After overnight fasting, rats ran on a treadmill at a speed of 28 m/min for 60 min, and were killed before and immediately, 1, 3, 6, 12, and 24 h after exercise. REDD1 mRNA and corresponding protein levels increased rapidly immediately after exercise, and gradually decreased back to the basal level over a period of 6 h in the gastrocnemius muscle. Phosphorylation of mTOR Ser2448 and S6K1 Thr389 increased with the exercise, but diminished in 1–3 h into the recovery period after cessation of exercise. The rate of protein synthesis, as determined by the surface sensing of translation (SUnSET) method, was not altered by exercise in fasted muscle. These results suggest that REDD1 attenuates exercise?induced mTORC1 signaling. This may be one mechanism responsible for blunting muscle protein synthesis during exercise and in the early postexercise recovery period. PMID:25539833

Hayasaka, Miki; Tsunekawa, Haruka; Yoshinaga, Mariko; Murakami, Taro

2014-01-01

373

Exercise-Induced Neuroprotection in the Spastic Han Wistar Rat: The Possible Role of Brain-Derived Neurotrophic Factor  

PubMed Central

Moderate aerobic exercise has been shown to enhance motor skills and protect the nervous system from neurodegenerative diseases, like ataxia. Our lab uses the spastic Han Wistar rat as a model of ataxia. Mutant rats develop forelimb tremor and hind limb rigidity and have a decreased lifespan. Our lab has shown that exercise reduced Purkinje cell degeneration and delayed motor dysfunction, significantly increasing lifespan. Our study investigated how moderate exercise may mediate neuroprotection by analyzing brain-derived neurotrophic factor (BDNF) and its receptor TrkB. To link BDNF to exercise-induced neuroprotection, mutant and normal rats were infused with the TrkB antagonist K252a or vehicle into the third ventricle. During infusion, rats were subjected to moderate exercise regimens on a treadmill. Exercised mutants receiving K252a exhibited a 21.4% loss in Purkinje cells compared to their controls. Cerebellar TrkB expression was evaluated using non-drug-treated mutants subjected to various treadmill running regimens. Running animals expressed three times more TrkB than sedentary animals. BDNF was quantified via Sandwich ELISA, and cerebellar expression was found to be 26.6% greater in mutant rats on 7-day treadmill exercise regimen compared to 30 days of treadmill exercise. These results suggest that BDNF is involved in mediating exercise-induced neuroprotection. PMID:25710032

Van Kummer, Brooke H.; Cohen, Randy W.

2015-01-01

374

Effective treatment of mitochondrial myopathy by nicotinamide riboside, a vitamin B3  

PubMed Central

Nutrient availability is the major regulator of life and reproduction, and a complex cellular signaling network has evolved to adapt organisms to fasting. These sensor pathways monitor cellular energy metabolism, especially mitochondrial ATP production and NAD+/NADH ratio, as major signals for nutritional state. We hypothesized that these signals would be modified by mitochondrial respiratory chain disease, because of inefficient NADH utilization and ATP production. Oral administration of nicotinamide riboside (NR), a vitamin B3 and NAD+ precursor, was previously shown to boost NAD+ levels in mice and to induce mitochondrial biogenesis. Here, we treated mitochondrial myopathy mice with NR. This vitamin effectively delayed early- and late-stage disease progression, by robustly inducing mitochondrial biogenesis in skeletal muscle and brown adipose tissue, preventing mitochondrial ultrastructure abnormalities and mtDNA deletion formation. NR further stimulated mitochondrial unfolded protein response, suggesting its protective role in mitochondrial disease. These results indicate that NR and strategies boosting NAD+ levels are a promising treatment strategy for mitochondrial myopathy. PMID:24711540

Khan, Nahid A; Auranen, Mari; Paetau, Ilse; Pirinen, Eija; Euro, Liliya; Forsström, Saara; Pasila, Lotta; Velagapudi, Vidya; Carroll, Christopher J; Auwerx, Johan; Suomalainen, Anu

2014-01-01

375

PI(5)P regulates autophagosome biogenesis.  

PubMed

Phosphatidylinositol 3-phosphate (PI(3)P), the product of class III PI3K VPS34, recruits specific autophagic effectors, like WIPI2, during the initial steps of autophagosome biogenesis and thereby regulates canonical autophagy. However, mammalian cells can produce autophagosomes through enigmatic noncanonical VPS34-independent pathways. Here we show that PI(5)P can regulate autophagy via PI(3)P effectors and thereby identify a mechanistic explanation for forms of noncanonical autophagy. PI(5)P synthesis by the phosphatidylinositol 5-kinase PIKfyve was required for autophagosome biogenesis, and it increased levels of PI(5)P, stimulated autophagy, and reduced the levels of autophagic substrates. Inactivation of VPS34 impaired recruitment of WIPI2 and DFCP1 to autophagic precursors, reduced ATG5-ATG12 conjugation, and compromised autophagosome formation. However, these phenotypes were rescued by PI(5)P in VPS34-inactivated cells. These findings provide a mechanistic framework for alternative VPS34-independent autophagy-initiating pathways, like glucose starvation, and unravel a cytoplasmic function for PI(5)P, which previously has been linked predominantly to nuclear roles. PMID:25578879

Vicinanza, Mariella; Korolchuk, Viktor I; Ashkenazi, Avraham; Puri, Claudia; Menzies, Fiona M; Clarke, Jonathan H; Rubinsztein, David C

2015-01-22

376

[Biogenesis of melanosomes - the chessboard of pigmentation].  

PubMed

Melanosomes are lysosome-related organelles in retinal pigment epithelial cells and epidermal melanocytes in which melanin pigments are synthesized and stored. Melanosomes are generated by multistep processes in which an immature unpigmented organelle forms and then subsequently matures. Such maturation requires inter-organellar transport of protein cargos required for pigment synthesis but also recruitment of effector proteins necessary for the correct transport of melanosomes to the cell periphery. Several studies have started to unravel the main pathways and mechanisms exploited by melanosomal proteins involved in melanosome structure and melanin synthesis. A major unexpected finding seen early in melanosome biogenesis showed the similarities between the fibrillar sheets of premelanosomes and amyloid fibrils. Late steps of melanosome formation are dependent on pathways regulated by proteins encoded by genes mutated in genetic diseases such as the Hermansky-Pudlak Syndrom (HPS) and different types of albinism. Altogether the findings from the past recent years have started to unravel how specialized cells integrate unique and ubiquitous molecular mechanisms in subverting the endosomal system to generate cell-type specific structures and their associated functions. Further dissection of the melanosomal system will likely shed light not only on the biogenesis of lysosome-related organelles but also on general aspects of vesicular transport in the endosomal system. PMID:21382323

Delevoye, Cédric; Giordano, Francesca; van Niel, Guillaume; Raposo, Graça

2011-02-01

377

Distinct Pathways Mediate the Sorting of Tail-anchored Mitochondrial Outer Membrane Proteins  

Technology Transfer Automated Retrieval System (TEKTRAN)

Little is known about the biogenesis of tail-anchored (TA) proteins localized to the mitochondrial outer membrane in plant cells. To address this issue, we screened all of the (>600) known and predicted TA proteins in Arabidopsis thaliana for those annotated, based on Gene Ontology, to possess mitoc...

378

Exercise-Induced Anaphylaxis: A Case Report and Review of the Diagnosis and Treatment of a Rare but Potentially Life-Threatening Syndrome  

PubMed Central

A 24-year-old male Marine with an uncomplicated medical history and a long history of strenuous, daily exercise presented to the emergency department after experiencing anaphylactic shock while running. Symptoms resolved following administration of intramuscular diphenhydramine, ranitidine, intravenous methylprednisolone, and intravenous fluids. On followup in the allergy clinic, a meticulous clinical history was obtained which elucidated a picture consistent with exercise-induced anaphylaxis. He had experienced diffuse pruritus and urticaria while exercising on multiple occasions over the last three years. His symptoms would usually increase as exercise continued. Prior to the first episode, he regularly exercised without symptoms. Exercise-induced anaphylaxis is a rare but potentially life-threatening syndrome that requires a careful clinical history and is a diagnosis of exclusion. Treatment is primarily exercise avoidance. Prophylactic mediations are inconsistently effective but are empirically used. Successful treatment with omalizumab was recently reported in a case of refractory exercise-induced anaphylaxis. PMID:23585764

Jaqua, Nathan T.; Peterson, Matthew R.; Davis, Karla L.

2013-01-01

379

Application of cytoplasmic Ca2+ fluorescence imaging techniques to study the molecular mechanisms of exercise-induced fatigue eliminated by Chinese medicine ginseng extract  

NASA Astrophysics Data System (ADS)

The exercise-induced fatigue eliminated by Chinese medicine offers advantages including good efficiency and smaller side-effects, however, the exact mechanisms have not been classified. A lot of literatures indicated the cytosolic free Ca2+ concentrations of skeletal muscle cells increased significantly during exercise-induced fatigue. This study is aimed to establish a rat skeletal muscle cell model of exercise-induced fatigue. We applied cytoplasmic Ca2+ fluorescence imaging techniques to study the molecular mechanisms of exercise-induced fatigue eliminated by Chinese medicine ginseng extract. In our research, the muscle tissues from the newborn 3 days rats were taken out and digested into cells. The cells were randomly divided into the ginseng extract group and the control group. The cells from the two groups were cultured in the medium respectively added 2mg/ml ginseng extract and 2mg/ml D-hanks solution. After differentiating into myotubes, the two groups of cells treated with a fluorescent probe Fluo-3 AM were put on the confocal microscope and the fluorescence intensity of cells pre- and post- stimulation with dexamethasone were detected. It was found that cytoplasmic Ca2+ concentrations of the two groups of cells both increased post-stimulation, however, the increasing amplitude of fluorescence intensity of the ginseng extract group was significantly lower than that of the control group. In conclusion, stimulating the cells with dexamethasone is a kind of workable cell models of exercise-induced fatigue, and the molecular mechanisms of exercise-induced fatigue eliminated by ginseng extract may be connected to regulatating cytosolic free Ca2+ concentrations.

Liu, Yi; Zhao, Yanping; Zhang, Heming; Liu, Songhao

2009-11-01

380

Necrostatin-1 mitigates mitochondrial dysfunction post-spinal cord injury.  

PubMed

Necrostatin-1 (Nec-1) is an inhibitor of necroptosis, playing an important role in inhibition of pathological death in the central nervous system (CNS). Our earlier study suggests that Nec-1 protects the injured spinal cord. In this study, we found that Nec-1 reduces the elevated Ca(2+) concentration in mitochondria post-injury and preserves the remarkably decreased mitochondrial membrane potential (MMP) level post-spinal cord injury (SCI). It also increases the generation of adenosine triphosphate (ATP) by promoting the activity of mitochondrial respiratory chain complex I instead of other complexes, which are significantly decreased due to the injury. Nec-1 also inhibits the release of cytochrome c in the mitochondria and protects the spinal cord from mitochondrial swelling post-SCI. Nec-1 promotes mitochondrial biogenesis by up-regulating mitochondrial transcription factor A (Tfam), in accordance with the mtDNA content. It also inhibits the up-regulation of mitochondrial fusion genes Mnf1, Mnf2 within 6h post-injury and adjusts the abnormal expression of mitochondrial fission gene Fis1. All these results indicate the improvement of mitochondrial functions in injured spinal cord after the treatment of Nec-1. This research revealed the mechanisms of functional protection of Nec-1 by mitigating mitochondrial dysfunction post-SCI. PMID:25595990

Wang, Y; Wang, J; Yang, H; Zhou, J; Feng, X; Wang, H; Tao, Y

2015-03-19

381

Resveratrol improves high-fat diet induced insulin resistance by rebalancing subsarcolemmal mitochondrial oxidation and antioxidantion.  

PubMed

Although resveratrol (RES) is thought to be a key regulator of insulin sensitivity in rodents, the exact mechanism underlying this effect remains unclear. Therefore, we sought to investigate how RES affects skeletal muscle oxidative and antioxidant levels of subsarcolemmal (SS) and intermyofibrillar (IMF) mitochondrial populations in high-fat diet (HFD)-induced insulin resistance (IR) rats. Systemic and skeletal muscle insulin sensitivity together with expressions of several genes related to mitochondrial biogenesis and skeletal muscle SIRT1, SIRT3 protein levels were studied in rats fed a normal diet, a HFD, and a HFD with intervention of RES for 8 weeks. Oxidative stress levels and antioxidant enzyme activities were assessed in SS and IMF mitochondria. HFD fed rats exhibited obvious systemic and skeletal muscle IR as well as decreased SIRT1 and SIRT3 expressions, mitochondrial DNA (mtDNA), and mitochondrial biogenesis (p?mitochondrial antioxidant enzyme activities were significantly lower, while IMF mitochondrial antioxidant enzyme activities were higher (p?mitochondrial biogenesis (p?mitochondrial antioxidant enzymes were increased, which reverted the increased SS mitochondrial oxidative stress levels (p?mitochondrial oxidative stress and antioxidant competence in HFD rats. PMID:25686565

Haohao, Zhang; Guijun, Qin; Juan, Zheng; Wen, Kong; Lulu, Chen

2015-03-01

382

Mitochondrial Diseases  

PubMed Central

Mitochondria contain the respiratory chain enzyme complexes that carry out oxidative phosphorylation and produce the main part of cellular energy in the form of ATP. Although several proteins related with signalling, assembling, transporting, and enzymatic function can be impaired in mitochondrial diseases, most frequently the activity of the respiratory chain protein complexes is primarily or secondarily affected, leading to impaired oxygen utilization and reduced energy production. Mitochondrial diseases usually show a chronic, slowly progressive course and present with multiorgan involvement with varying onset between birth and late adulthood. Neuromuscular system is frequently affected in mitochondrial diseases. Although there is actually no specific therapy and cure for mitochondrial diseases, the understanding of the pathophysiology may further facilitate the diagnostic approach and open perspectives to future in mitochondrial diseases. PMID:24649452

Lee, Young-Mock

2012-01-01

383

Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles  

PubMed Central

Congestive heart failure (CHF) induces alterations in energy metabolism and mitochondrial function that span cardiac as well as skeletal muscles. Whether these defects originate from altered mitochondrial DNA copy number and/or mitochondrial gene transcription is not known at present, nor are the factors that control mitochondrial capacity in different muscle types completely understood. We used an experimental model of CHF induced by aortic banding in the rat and investigated mitochondrial respiration and enzyme activity of biochemical mitochondrial markers in cardiac, slow and fast skeletal muscles. We quantified mitochondrial DNA (mtDNA), expression of nuclear (COX IV) and mitochondrial (COX I) encoded cytochrome c oxidase subunits as well as nuclear factors involved in mitochondrial biogenesis and in the necessary coordinated interplay between nuclear and mitochondrial genomes in health and CHF. CHF induced a decrease in oxidative capacity and mitochondrial enzyme activities with a parallel decrease in the mRNA level of COX I and IV, but no change in mtDNA content. The expression o