Cancer-related inflammation profoundly affects tumor progression. Tumor-associated macrophages (TAMs) are known regulators of that inflammation, but the factors that initiate cancer-related inflammation are poorly understood. Tumor invasiveness and poor clinical outcome are linked to increased expression of cell surface-associated vacuolar adenosine triphosphatases. The a2 ...
PubMed
Crescentic glomerulonephritis (GN) in Wistar-Kyoto rats progresses to lethal kidney failure by macrophage (M?)-mediated mechanisms. M?s in nephritic glomeruli express adenosine A(2A) receptors (A(2A)Rs), the activation of which suppresses inflammation. Here, we ...
The cleavage of the A2 domain of von Willebrand factor (VWF) by the metalloprotease ADAMTS13 regulates VWF size and platelet thrombosis rates. Reduction or inhibition of this enzyme activity leads to thrombotic thrombocytopenic purpura (TTP). We generated a set of novel molecules called VWF-A2 FRET (fluorescence/F�rster resonance energy transfer) ...
... Accession Number : ADA446371. Title : Castration-Induced Neuroendocrine Mediated Progression of Prostate Cancer. ...
DTIC Science & Technology
... Accession Number : ADA492892. Title : Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer. Descriptive ...
EphA2 kinase regulates cell shape, adhesion, and motility and is frequently overexpressed in several cancers, including melanoma, prostate, breast, and colon cancers and lung carcinoma. Although a function in both tumor onset and metastasis has been proposed, the role played by EphA2 in tumor progression is still debated. In melanoma, ...
2,3,7,8-Tetrachlordibenzo-p-dioxin (TCDD)-Mediated Oxidative Stress in Female CYP1A2 Knockout (CYP1A2-/-) Mice Deborah Burgin1, Janet Diliberto2, Linda Birnbaum2 1UNC Toxicology; 2USEPA/ORD/NHEERL, RTP, NC Most of the effects due to TCDD exposure are mediated via...
EPA Science Inventory
SUMMARYBoth pro- and anti-oncogenic properties have been attributed to EphA2 kinase. We report that a possible cause for this apparent paradox is diametrically opposite roles of EphA2 in regulating cell migration and invasion. While activation of EphA2 with its ligand ephrin-A1 inhibited chemotactic migration of glioma and prostate cancer cells, EphA2 ...
PubMed Central
... Thromboxane synthase is an enzyme downstream cyclooxygenase, utilizing prostaglandin H to form thromboxane A2. ...
Our previous study [Bhave, V. S., Donthamsetty, S., Latendresse, J. R., Muskhelishvili, L., and Mehendale, H. M. 2008-this issue. Secretory phospholipase A(2) mediates progression of acute liver injury in the absence of sufficient COX-2. Toxicol Appl Pharmacol] showed that in the absence of sufficient induction and ...
The activation of phospholipase A2 is believed to have an important role in the inflammatory process owing to its induction of eicosanoids, platelet activating factor, and other mediators. Soluble phospholipase A2 has been associated with exudates in different inflammatory conditions. In this ...
BackgroundThe canonical function of EEF1A2, normally expressed only in muscle, brain, and heart, is in translational elongation, but recent studies suggest a non-canonical function as a proto-oncogene that is overexpressed in a variety of solid tumors including breast and ovary. Transcriptional profiling of a spectrum of primary mouse B cell lineage neoplasms showed that transcripts encoding ...
Ligand-activated Eph tyrosine kinases regulate cellular repulsion, morphology, adhesion, and motility. EphA2 kinase is frequently up-regulated in several different types of cancers, including prostate, breast, colon, and lung carcinomas, as well as in melanoma. The existing data do not clarify whether EphA2 ...
We propose that expression of four genes encoding secretory phospholipases A2 (sPLA2) mediates insect nodulation responses to bacterial infection. Nodulation is the quantitatively predominant cellular defense reaction to bacterial infection. This reaction is mediated by eicosanoids, the biosynthesis...
Technology Transfer Automated Retrieval System (TEKTRAN)
... addition, these vitamin D3 metabolites mediate their effects in a cell maturation-dependent manner through activation of protein kinase C (PKC), ...
... Support for this study was provided by Contract NOIR 225(a2), Project NR 177 254, Group Psyehology Branch, Office of Naval Research. ...
... Reasons for not performing an immunologic assay included utilization of cells in alternate experiments, cell loss during transit, collection of ...
... Significant gamma interferon production, determined by enzyme-linked immunospot assay to at least one of the three peptide pools, was observed ...
... of Both Prostate Cancer Cell Motility and Growth ... integrin-mediated cell migration. ... Descriptors : *PEPTIDES, *CELLS(BIOLOGY), *METASTASIS ...
Phospholipases A(2) (PLA(2)s) are essential enzymes in cells. They are not only responsible for maintaining the structural organization of cell membranes, but also play a pivotal role in the regulation of cell functions. Activation of PLA(2) s results in the release of fatty acids and lysophospholipids, products that are lipid ...
Thromboxane A2 (TxA2) has been implicated as a potential mediator of myocardial damage during acute ischemia. A potent and specific TxA2 receptor antagonist, SQ-29,548 (2 mg/kg bolus + 2 mg/kg/h) was tested in a cat acute coronary ligation model of ...
... Accession Number : ADA476747. Title : Castration Induced Neuroendocrine Mediated Progression of Prostate Cancer. Descriptive Note : Final rept. ...
Ovarian epithelial carcinomas (OEC) frequently exhibit amplifications at the 20q13 locus which is the site of several oncogenes, including the eukaryotic elongation factor EEF1A2 and the transcription factor ZNF217. We reported previously that overexpressed ZNF217 induces neoplastic characteristics in precursor cells of OEC. Unexpectedly, ZNF217, which is ...
DOE Information Bridge
Cytoplasmic transport and localization of mRNA has been reported for a range of oocytes and somatic cells. The heterogeneous nuclear ribonucleoprotein (hnRNP) A2 response element (A2RE) is a 21-nucleotide segment of the myelin basic protein mRNA that is necessary and sufficient for cytoplasmic transport of this ...
The Eph subfamily of receptor tyrosine kinases and their membrane-anchored ephrin ligands mediate cell-cell contact signaling and are versatile regulators of cell migration and tissue patterning, which are often exploited by cancer cells during tumor progression. New evidence shows that prostate cancer cells use ...
and test whether youth's educational expectations mediate the relationships between assets and college to college progress. We also hypothesize that youth's educational expectations mediate the relationships suggest that youth's college expectations partially mediate the relationship between youth school savings
E-print Network
Tissue plasminogen activator (tPA) is absent from normal human pancreas and is expressed in 95% of human pancreatic adenocarcinomas. We have analyzed the expression of components of the tPA system in murine pancreatic tumors and the role of tPA in neoplastic progression. Transgenic mice expressing T antigen and c-myc under the control of the elastase promoter (Ela1-TAg and ...
Phospholipase A2 (EC 3.1.1.4) is a key enzyme in inflammation and is thought to play an important part in inflammatory diseases of the gastrointestinal tract. To investigate the nature and regulation of phospholipase A2 activity in the gastrointestinal mucosa, the distribution of messenger ribonucleic acid (mRNA) ...
The initiation and progression of prostate cancer remain not well understood to enable development of interventional therapy. Thromboxane synthase is an enzyme downstream of cyclooxygenase, utilizing prostaglandin H to form thromboxane A2. Using immunohis...
National Technical Information Service (NTIS)
Tissue plasminogen activator (tPA) is overexpressed in pancreatic ductal carcinoma and is involved in tumor progression. This effect is probably mediated through the activation of angiogenesis, cell invasion, and cell proliferation. Previous studies support the notion that the effects of tPA on cell invasion require its proteolytic activity. Here, we ...
The ligand-activated nuclear receptor PXR is known to play a role in the regulated expression of drug metabolizing enzymes and transporters. Recent studies suggest a potential clinically relevant role of PXR in breast cancer. However, the relevant pathway or target genes of PXR in breast cancer biology and progression have not yet been fully clarified.In this study, we show ...
Cigarette smoking is a major cause of mortality and morbidity worldwide. Cyclooxygenase (COX) and its derived prostanoids, mainly including prostaglandin E2 (PGE2), thromboxane A2 (TxA2) and prostacyclin (PGI2), have well-known roles in cardiovascular disease and cancer, both of which are associated with cigarette ...
Annexin A2 is a calcium-dependent, phospholipid-binding protein found on various cell types. It is up-regulated in various tumor types and plays multiple roles in regulating cellular functions, including angiogenesis, proliferation, apoptosis, cell migration, invasion and adhesion. Annexin A2 binds with plasminogen ...
Summary.? Platelet adhesion, activation and aggregation on the exposed subendothelial extracellular matrix (ECM) are essential for haemostasis, but may also lead to occlusion of diseased vessels. Binding of the glycoprotein (GP)Ib-V-IX complex to immobilised von Willebrand factor (VWF) initiates adhesion of flowing platelets to the ECM, and thereby enables the collagen receptor GPVI to interact ...
Cellular senescence involves a reduction in adult stem cell self-renewal, and epigenetic regulation of gene expression is one of the main underlying mechanisms. Here, we observed that the cellular senescence of human umbilical cord blood-derived multipotent stem cells (hUCB-MSCs) caused by inhibition of histone deacetylase (HDAC) activity leads to down-regulation of high mobility group ...
The full amino acid sequence of the acidic phospholipase A2 from Indian cobra (Naja naja naja) venom was determined and its tertiary structure examined by circular dichroism (CD). The sequence was aligned with other sequences of secreted phospholipase A2 from snakes of the genus Naja, using the ...
Glucocorticoid receptors in cytosol preparations from rat liver or mouse L cells are inactivated by phospholipase A2 or calf intestine alkaline phosphatase. Molybdate ion, an inhibitor of a variety of phosphatase enzymes, does not prevent inactivation of glucocorticoid binding capacity by alkaline phosphatase but it blocks inactivation by phospholipase ...
arachidonic acid release in H9c2 rat cardiomyocyte cells in response to hydrogen peroxide Michelle V. Winstead release arachidonic acid in response to hydrogen peroxide. In H9c2 cells, arachidonic acid release2 Group IV enzyme mediates arachidonic acid mobilization. Moreover, hydrogen peroxide alters
Evidence for an Aryl Hydrocarbon Receptor-Mediated Cytochrome P450 Autoregulatory Pathway-1 cells through transient transfection with various cytochrome P450 isoforms. Expression of cytochromes P450 1A1, 1A2, or 1B1 reduced AhR-mediated luciferase reporter activity, whereas cytochrome P450 2
This investigation is to delete the most of the coding sequence (1104 bp) of the IV a2 gene in an adenovirus genome by a lambda-Red recombinase system-mediated PCR-targeting approach and rescue a recombinant adenovirus with IV a2 deletion. First, the template pAK of PCR targeting, containing ...
Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer related death in Western men. In prostate intraepithelial neoplasia annexin A2 expression is absent however upon loss of androgen dependence annexin A2 is subsequently over-expressed. Regaining regulatory control of ...
Annexin A2 (p36) is usually present together with its natural ligand p11 as a heterotetramer complex, which has multiple biological functions depending on its cellular localization. However, the detailed mechanism of annexin A2 translocation and its physiological role in inflammation remain unclear. Here, we show ...
molecule adenosine. In mammals, adenosine assumes an essential role in regulating innate and acquired, but only adenosine is able to completely suppress immune responses (N�meth et al., 2006). The immunoregulatory attributes of adenosine are mediated via four transmembrane adenosine receptors: A1, A2A, ...
underlying the pathophysiology of Alzheimer's disease (AD) is the production of cytotoxic amyloid- (A:2040�2041. Chauhan V, Chauhan A (2006) Oxidative stress in Alzheimer's disease. Pathophysiology 13:195�208. Christen pathophysiology. Curr Alzheimer Res 2:403�408. Murakami M, Kudo I (2002) Phospholipase A2. J Biochem (Tokyo) 131
Activation of phospholipase A2 (PLA2) by the aggregation of receptors for immunoglobulin E (IgE) can be studied in streptolysin O-permeabilized rat basophilic leukemia cells. Under these conditions, 40 micrograms guanosine 5'-O-(3-thio)triphosphate stimul...
). Recent data have shown differential ex- pression of sPLA2s IID, III, and V but not X in human colonGroup X Phospholipase A2 Stimulates the Proliferation of Colon Cancer Cells by Producing Various diseases such as athero- sclerosis and asthma and may also play a role in colon tumor- igenesis. We show
and fibroblast mitogenic regulatory activity. TxA 2 is a pathophysiologically significant BK-evoked me- diator produce pathophysiologic quantities of mediators such as TxA 2, independent of BK receptor mechanisms in Alzheimer's disease, including prote- olytic processing of the amyloid ...
, such as hypertension. This is an un-copyedited author manuscript that was accepted for publication in Hypertension manuscript Hypertension 06/2004; 43(6): 1264-9 #12;2 INTRODUCTION Thromboxane A2 (TxA2), a lipid mediator cardiovascular diseases such as unstable angina (2), acute myocardial ...
... Accession Number : ADA469370. Title : In vivo RNAi Library Screen to Identify Mediators of Disease Progression and Drug Resistance in CML. ...
Alterations in sialylation are well documented in breast cancer as well as other epithelial cancers. A principal enzyme implicated in this process is the sialyltransferase ST6Gal, which mediates the synthesis of the sialyl a2, 6-anomeric linkage to termin...
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Annexin A2 is a highly expressed gene with important roles in cell membrane physiology and is frequently dysregulated in cancer. The objective of this study was to determine the pattern of expression and prognostic significance of annexin A2 protein in head and neck squamous cell carcinoma. We assessed both ...
Adenosine is released during tissue injury, ischemia and tumor growth, and promotes angiogenesis. Because mast cells accumulate in the proximity of new blood vessel development, we examined if they may contribute to adenosine-induced angiogenesis. We found that HMC-1 human mast cells express A2A, A2B, and A3 ...
Accomplishments for the past quarter are briefly described for: task A.2.1 on criticality studies and drift emplacement model; and for task A.2.2. on waste container alternate design considerations.
This document contains a complete set of valid and final digital and analog data plots for LLTR Series II, Test A-2. Included is an Accuracy Statement regarding this data as required by Revision 0 of the GE Test Request, Specification No. 23A2062. The Ser...
... between the two pathways and furthermore, that activation of a growth factor pathway is required for estradiol mediated stimulation of proliferation. ...
... Work on this section not completed yet. b. Determine the paraerine effect in soft agar tumorgenesis. Colony formation of ...
Leukotrienes (LTs), derived from arachidonic acid (AA) released from the membrane by the action of phospholipase A(2), are potent lipid mediators of the inflammatory response. In 1983, Dahl�n et al. demonstrated that LTC(4), LTD(4), and LTE(4) mediate antigen-induced constriction of bronchi in tissue obtained ...
The conversion of castasterone (CS) to brassinolide (BL), a Baeyer-Villiger oxidation, represents the final and rate-limiting step in the biosynthesis of BL in plants. Heterologously expressed Arabidopsis thaliana CYP85A2 in yeast mediated the conversion of CS to BL as well as the C-6 oxidation of brassinosteroids (BRs). This indicated ...
This paper deals with the changing family structures and perceptions of family within our society and its correlative changes within the life of the children and youth. A practical example introduces the reader into the processes of mediation between parents and youth from its progression to the agreement. For the planning of mediation ...
We have previously shown that recombinant interleukin 1 (IL-1) and recombinant tumour necrosis factor (TNF) synergistically stimulate phospholipase A2 release from mesangial cells. We now report that treatment of mesangial cells with the beta-agonist salbutamol, prostaglandin E2 (PGE2), cholera toxin or forskolin, which all activate adenylate cyclase, ...
The aggressiveness of pancreatic ductal adenocarcinoma (PDA) is characterized by its high metastatic potential and lack of effective therapies, which is the result of a lack of understanding of the mechanisms involved in promoting PDA metastases. We identified Annexin A2 (ANXA2), a member of the ...
PurposeClinical observations have suggested that shedding of the MHC class I chain-related molecule (MIC) may be one of the mechanisms by which tumors evade host immune surveillance and progress. However, this hypothesis has never been proven. In this study, we tested this hypothesis using a prostate tumor model and investigated the impact of shedding of MIC on tumor ...
Cytosolic phospholipase A(2)-alpha (cPLA(2)-alpha) is a calcium-sensitive enzyme involved in receptor-mediated eicosanoid production. In resting cells, cPLA(2)-alpha is present in the cytosol and nucleus and translocates to membranes via its calcium-dependent lipid-binding (CaLB) domain following stimulation. cPLA(2)-alpha is also ...
Heterogeneous nuclear ribonucleoprotein B1, an RNA binding protein, is overexpressed from the early stage of lung cancers; it is evident even in bronchial dysplasia, a premalignant lesion. We evaluated the proteins bound with hnRNP B1 and found that hnRNP B1 interacted with DNA-dependent protein kinase (DNA-PK) complex, and recombinant hnRNP B1 protein dose-dependently inhibited DNA-PK activity in ...
Energy Citations Database
Platelet-activating factor (PAF), a mediator of proatherosclerotic inflammatory processes, is also implicated in endothelial dysfunction during human immunodeficiency virus (HIV) infection. We examined PAF metabolism in blood of naive male patients, 8 with early HIV infection (group A) and 17 just before treatment initiation (group B), versus 18 healthy age-matched males ...
Here we have used siRNAs and time-lapse epifluorescence microscopy to examine the roles of various candidate mitotic cyclins in chromatin condensation in HeLa cells. Knocking down cyclin A2 resulted in a substantial (?7 h) delay in chromatin condensation and histone H3 phosphorylation, and expressing an siRNA-resistant form of cyclin ...
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that is kept in a zoonotic transmission cycle between pigs and mosquitoes. JEV causes infection of the central nervous system with a high mortality rate to dead-end hosts, including humans. Many studies have suggested that the flavivirus core protein is not only a component of nucleocapsids but also an important pathogenic ...
Annexin A2 and heparin bind to one another with high affinity and in a calcium-dependent manner, an interaction that may play a role in mediating fibrinolysis. In this study, three heparin-derived oligosaccharides of different lengths were co-crystallized with annexin A2 to elucidate the ...
Cytochrome P450 1A2 (CYP1A2) is constitutively expressed in the mouse liver, but the constitutive expression progressively declines to an undetectable level in isolated hepatocytes. In this study, CYP1A2 was induced in hepatocytes exposed to the histone ...
BACKGROUND: Adenosine has been shown to inhibit cell growth and induce apoptosis in the several cancer cells via intrinsic and extrinsic pathway. The present study was designed to understand the mechanism underlying adenosine-induced apoptosis in the DU-145, PC3, and LNcap-FGC10 human prostate cancer cells. METHODS: To observe cell viability and proliferation, MTT assay, cell counting, and BrdU ...
This Prostate Cancer Center initiation grant has been designed to identify genetic and molecular markers of prostate cancer progression within and between racial ethnic groups (African-Americans, Latinos, Whites, Japanese) at substantially distinct underl...
; and Division of Nephrology, Department of Medicine, Duke University, and Durham VA Medical Centers, DurhamThromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure, North Carolina Abstract. Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2
The release of arachidonic acid (AA) and platelet activating factory (PAF) from airway epithelial cells may be an important mediating factor in lung physiological and inflammatory processes. The type of lung response may be determined by the directional release of AA and PAF. We ...
Understanding HLA-restricted adaptive host immunity to defined epitopes of malarial antigens may be required for the development of successful malaria vaccines. Fourteen epitopes of preerythrocytic malarial antigens known to mediate cytotoxic T-lymphocyte...
Several regulatory proteins control cell cycle progression. These include Emi1, an anaphase-promoting complex (APC) inhibitor whose destruction controls progression through mitosis to G1, and p21WAF1, a cyclin-dependent kinase (CDK) inhibitor activated by DNA damage. We have analyzed the role of p21WAF1 in G2-M ...
Tumour necrosis factor (TNF) is an important mediator of endotoxin-induced vascular collapse and other inflammatory reactions. Eicosanoids have been implicated in the pathogeensis of these responses. In order to explore further the potential interactions between TNF and eicosanoid metabolism in eliciting vascular responses, we studied the effects of TNF on the bovine ...
ABSTRACT-Here we identify release of annexin A2 into the culture medium in response to low dose X-ray radiation exposure and establish functional linkages to an established paracrine factor-mediated anchorage-independent growth response. Using a standard bicameral coculture model, we observe that annexin ...
The role of the vascular endothelium in progressive renal disease is not well understood. This review presents evidence that progressive renal disease is characterized by a progressive loss of the microvasculature. The loss of the microvasculature correlates directly with the development of glomerular and tubulointerstitial scarring. ...
Efficient execution of apoptotic cell death followed by efficient clearance mediated by professional macrophages is a key mechanism in maintaining tissue homeostasis. Removal of apoptotic cells usually involves three central elements: 1) attraction of phagocytes via soluble "find me" signals, 2) recognition and phagocytosis via cell surface-presenting "eat me" signals, and 3) ...
Although there have been a number of recent studies on the role of Rac in the generation of reactive oxygen species (ROS), details of the signalling pathway remain unclear. In the present study we analysed the extent to which the activation of cytosolic phospholipase A(2) and the resultant release of arachidonic acid (AA) are involved in the ...
Crystal of Russell Viper venom phospholipase A(2) complexed with an isoquinoline alkaloid, berberine from a herbaceous plant Cardiospermum halicacabum, was prepared and its structure was solved by X-ray crystallography. The crystal diffracted up to 1.93� and the structure solution clearly located the position of berberine in the active site of the ...
Geminin is an essential cell-cycle protein that is only present from S phase to early mitosis in metazoan somatic cells. Genetic ablation of geminin in the mouse results in preimplantation embryonic lethality because pluripotent cells fail to form and all cells differentiate to trophoblast. Here we show that geminin is present in G1 phase of mouse pluripotent cells in contrast to somatic cells, ...
SummaryGeminin is an essential cell-cycle protein that is only present from S phase to early mitosis in metazoan somatic cells [1,�2]. Genetic ablation of geminin in the mouse results in preimplantation embryonic lethality because pluripotent cells fail to form and all cells differentiate to trophoblast [3,�4]. Here we show that geminin is present in G1 phase of�mouse pluripotent cells in ...
Vascular tone is controlled by endothelium and nerves innervating blood vessels. Endothelium releases various substances such as PGI2 (Prostacyclin), NO (nitric oxide), TXA2 (thromboxane A2) and ET-1 (endothelin-1). It is well documented that ethanol affects vascular responses mediated by these substances. On the other hand, peripheral ...
The lateral organizations of receptors in the cell membrane display a tremendous amount of complexity. In some cases, receptor functions can be attributed to specific spatial arrangements in the plasma membrane. We recently found that one member of the largest subfamily of receptor tyrosine kinases (RTKs), EphA2, is organized over micrometer length scales ...
Endogenous mediators within the inflammatory milieu play a critical role in directing the scope, duration, and resolution of inflammation. High-molecular-weight extracellular matrix hyaluronan (HA) helps to maintain homeostasis. During inflammation, hyaluronan is broken down into fragments that induce chemokines and cytokines, thereby augmenting the inflammatory response. ...
Cytochrome P450 1A2 (CYP1A2) is an important member of cytochrome P450 involved in drug metabolism. In this study, a cell line, Huh7-1A2-I-E, with high expression level of CYP1A2 is established based on Huh7 cells. To achieve this, we constructed a recombinant lentiviral ...
The role of thromboxane A(2) (TxA(2)) in smoking-associated lung cancer is poorly understood. This study was conducted to study the role of TxA(2) in smoking carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-promoted cell survival and growth in human lung cancer cells. We found that NNK increased ...
Both A23187 and formyl-Met-Leu-Phe (fMLP) induced the release of arachidonic acid and the production of thromboxane B(2) and leukotriene B(4) from rat neutrophils that were inhibited by acetylshikonin in a concentration-dependent manner. Acetylshikonin blocked exogenous arachidonic acid-induced leukotriene B(4) and thromboxane B(2) production in neutrophils and inhibited the enzymatic activity of ...
An interaction between adenosine A(2A) receptors (A(2A) Rs) and cannabinoid CB(1) receptors (CB(1) Rs) has been consistently reported to occur in the striatum, although the precise mechanisms are not completely understood. As both receptors control striatal glutamatergic transmission, we now probed the putative ...
IgA nephropathy (IgAN) is generally thought to be mediated by the glomerular deposition of circulating immune complexes containing IgA as the major antibody component. Upper respiratory infections and tonsillitis often precede IgAN, and in some cases tonsillectomy is effective for the treatment of IgAN. Thus, the tonsil seems to be a unique organ causing initial and/or ...
HTLV-1 associated myelopathy/ tropical spastic paraparesis (HAM/TSP) is a systemic immune-mediated inflammatory disease and tissues other than nervous can be damaged, mainly ocular, rheumatic and dermatologic. Over 90% of HTLV-1-infected individuals remain lifelong asymptomatic and this retrovirus persists indefinitely in their CD4+ T-lymphocytes. The infection is maintained ...
We have investigated the effects of phospholipase A2 and C on the synthesis of prostaglandin E2 in rabbit kidney medulla and the release of fatty acids from the medulla slices. Exogenous phospholipase A2 [from Naja naja (Indian cobra) venom] and phospholipase C (from Clostridium welchii) stimulated prostaglandin E2 ...
Airway neutrophil infiltration is a pathological hallmark observed in multiple lung diseases including pneumonia and cystic fibrosis. Bacterial pathogens such as Pseudomonas aeruginosa instigate neutrophil recruitment to the air space. Excessive accumulation of neutrophils in the lung often contributes to tissue destruction. Previous studies have unveiled hepoxilin A(3) as the key molecular signal ...
Inhibition of cytochrome P-450 1A2 (CYP1A2)-mediated activation of procarcinogens may be an important chemopreventive mechanism. Consumption of apiaceous vegetables (rich in furanocoumarins) inhibits CYP1A2 in humans. Because many furanocoumarins are ...
Recent studies showed that soluble annexin A2 dramatically increases tissue plasminogen activator (tPA)-mediated plasmin generation in vitro, and reduces thrombus formation in vivo. Here, we hypothesize that combining annexin A2 with tPA can significantly enhance thrombolysis efficacy, so that ...
The acidic phospholipase A2 from Bothrops lanceolatus venom has been purified by gel filtration on Sephadex G-50 and ion exchange chromatography on CM-cellulose. Analysis by FPLC on Mono-Q column of the purified phospholipase A2 indicated that it is a mixture of several isoenzymes. The two major isoforms consist of ...
Phospholipase A2 (PLA2) from cobra (Naja naja) venom and PLA2 from porcine pancreas accelerated IgE antibody-mediated histamine release from rat peritoneal mast cells. These enhancements were clearly abrogated by heating the enzymes and pretreatment with parabromophenacyl bromide, mepacrine and antiflammin. Indomethacin (cyclooxygenase ...
The adenosine A(2A) receptor (A(2A) R) is a potential drug target for the treatment of Parkinson's Disease and other neurological disorders. In rodents, the therapeutic efficacy of A(2A) R modulation is improved by concomitant modulation of the metabotropic glutamate receptor 5 (mGluR5). To elucidate the anatomical ...
The membrane bound, sulfite sensitive, light effect mediator protein was identified and isolated from leaves of the pea. This protein appears to mediate the effect of SO sub 2 on plants. 2 refs. (ERA citation 11:006321)
The goal of this project was to gain a fundamental understanding of how calcium/calmodulin-mediated signaling is involved in gravity signal transduction in plants. During the period of support, significant progress was made in elucidating the role of calm...
The membrane bound, sulfite sensitive, light effect mediator protein was identified and isolated from leaves of the pea. This protein appears to mediate the effect of SO/sub 2/ on plants. 2 refs. (DT)
A disintegrin and metalloprotease with a thrombospondin type 1 motifs 13 (ADAMTS-13) regulates hemostasis by cleaving the folded A2 domain of von Willebrand factor (VWF). The cleavage is regulated by forces as it occurs in flowing blood. We tested the hypothesis that force-induced A2 domain unfolding facilitates ...
Recent advances in the study of RASSF1A, the candidate tumor suppressor gene, indicate a possible role of RASSF1A in cell cycle regulation; however, very little is known regarding molecular mechanisms underlying this control. Using small interfering RNA to knockdown endogenous RASSF1A in the breast tumor cell line HB2 and in the cervical cancer cell line HeLa, we identify that a key player in cell ...
The ethanol-inducible cytochrome P450 2E1 (CYP2E1) is also induced under different pathological and physiological conditions. Studies including ours have shown that CYP2E1 is bimodally targeted to both the endoplasmic reticulum (microsomes) (mc CYP2E1) and mitochondria (mt CYP2E1). In this study we investigated the role of mtCYP2E1 in ethanol-mediated oxidative stress in ...
alpha 1-Adrenergic receptors mediate two effects on phospholipid metabolism in Madin-Darby canine kidney (MDCK-D1) cells: hydrolysis of phosphoinositides and arachidonic acid release with generation of prostaglandin E2 (PGE2). The similarity in concentration dependence for the agonist (-)-epinephrine in eliciting these two responses implies that they are ...
In our study, ampicillin (AMP)-mediated decrease of enterobacteria caused increases in hepatic bile acid concentration through (at least in part) elevation of bile acid synthesis in C57BL/6N mice. We investigated the involvement of enterobacteria on intestinal bile acid absorption in AMP-treated mice in the present study. Fecal enterobacterial levels and fecal bile acid ...
We have previously identified the EphA2 receptor tyrosine kinase as a potentially important injury-responsive gene and a transcriptional target of Src kinase activity in renal ischemia-reperfusion injury (IRI). In the present study, we confirmed, using EphA2 gene trap mice that the endogenous EphA2 promoter is ...
PurposeCigarette smoking induces CYP1A1/1A2 and is hypothesized to alter erlotinib pharmacokinetics. This study aimed to determine the maximum tolerated dose (MTD) of erlotinib in advanced non�small-cell lung cancer (NSCLC) patients who smoke and compare the pharmacokinetics of erlotinib at the MTD in current smokers with 150 mg.Patients and ...
BackgroundThe amyloid-? (A?) peptide is the primary component of the extracellular senile plaques characteristic of Alzheimer's disease (AD). The metals hypothesis implicates redox-active copper ions in the pathogenesis of AD and the Cu2+ coordination of various A? peptides has been widely studied. A number of disease-associated modifications involving the first 3 residues ...
presence and empathy. Additionally, in "The Cyborg's Dilemma", Biocca (1997) highlights similar. The cyborg's dilemma: Progressive em- bodiment in virtual environments. Journal of Computer Mediated
... 2007 summary report, we have made significant progress in elucidating the novel mechanisms by which PR regulates expression of E2F1, a key ...
... Abstract : Parkinson's disease (PD) is characterized by progressive loss of ... neurotoxins inhibit complex I of the mitochondrial respiratory chain ...
Contents: Duration and spectral form as cues in the recognition of English and German vowels; perception of time intervals; pitch mediation by temporal mechanisms; experiments with delayed auditory feedback; formants in Vietnamese vowels of different tone...
... we examined AR- mediated PSA expression and promoter/enhancer occupancy after AR activation with the natural ligand DHT, the cytokine LL-6 ...
... The mechanisms for stimulation of cell cycle progression through G1 ... expression, Rb phosphorylation, nor the association of growth factor receptors ...
... effects of ERa restoration on AhR-mediated effects. ... induced gene expression and cell cycle progression in MCF-7 breast cancer cells. ...
Critical progress has been made in the identification and characterization of cells and mediators involved in allergic inflammation. Accumulating evidence supports the importance of cell adhesion molecule expression as an initiating process in tissue infl...
... mediator for retinoid and thyroid hormone receptors ... action in breast cancer cells were measured. ... led to tamoxifen-stimulated cell cycle progression ...
... individual NE cells surrounded by small foci of ... Non-invasive visualization of various receptors in NE ... to the biology of CaP: cell growth, migration ...
... EA A paradigm shift in the anagement of multicystic dysplastic kidney. ... invasion by inhibiting integrin-dependent crosstalk with c-Met receptor and ...
... We have shown that gastrin-releasing peptide prostate cancer cells have their growth in soft agar inhibited by the specific Src inhibitor AZD0530. ...
All four adenosine receptor subtypes have been shown to play a role in cardioprotection, and there is evidence that all four subtypes may be expressed in cardiomyocytes. There is also increasing evidence that optimal adenosine cardioprotection requires activation of more than one receptor subtype. The purpose of this study was to determine whether adenosine ...
A2-day international workshop on the progression and regression of carotid atherosclerosis. in clinical trials, sponsored by the Bowman Gray School of Medicine, was convened in August, 1989, in Winston-Salem, N.C. The objectives of the conference were to review 1) arterial anatomy as it relates to the etiology and ...
A2E, an important constituent of lipofuscin in human retinal pigment epithelium (RPE), is thought to mediate light-induced oxidative damage associated with aging and other ocular disorders. Ocular carotenoids in overlying retinal tissues were measured by HPLC and mass spectrometry and were correlated with levels of RPE ...
Fragile X associated tremor ataxia syndrome (FXTAS) is a recently described neurodegenerative disorder of older adult carriers of premutation alleles (60-200 CGG repeats) in the fragile-X mental retardation gene (FMR1). It has been proposed that FXTAS is an RNA mediated neurodegenerative disease caused by the titration of RNA binding proteins by the CGG repeats. To test this ...
AMPAR (?-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid receptor) is an ion channel involved in the formation of synaptic plasticity. However, the molecular mechanism that couples plasticity stimuli to the trafficking of postsynaptic AMPAR remains poorly understood. Here, we show that PIKE (phosphoinositide 3-kinase enhancer) GTPases regulate neuronal AMPAR activity by promoting ...
Arachidonic acid has been implicated as a second messenger in insulin secretion by islets of Langerhans. D-Glucose, the major physiological stimulus, increases unesterified arachidonate accumulation in islets. We now show, for the first time, that the muscarinic agonist carbachol, at concentrations which stimulate insulin secretion, causes a rapid and nearly 3-fold increase in arachidonic acid ...
This study investigates the proliferative effect of adenosine (ADO) in cultured mesangial cells, and the possible mediation of A1 and/or A2 receptors in this proliferative effect of ADO. ADO (10(-5) M) induced a significant increase in the [3H]thymidine incorporation into DNA with respect to quiescent cells. This increase was similar ...
In the past year tremendous progress has been made towards completing the tasks outlined in the original Statement of Work. The physical association between XIAP and AIF was confirmed in living cells, and it was further determined that XIAP-mediated caspa...
Observations from androgen ablation treatment of prostate cancer have shown that the androgen-signaling pathway is important in the growth and progression of prostate cancer. The growth-promoting effects of androgen are mediated mostly through the androge...
Progress has been made in the last year in evaluating photoresponsive polymer coated semiconductor electrodes as vehicles for redox mediation and as photoanodes in electrochemical cells. The incorporation of both anionic and cationic dyes into polymer-coa...
Progress is reported in the following research areas: (1) metabolic studies of Syntrophomonas wolfei; (2) evidence for a carrier-mediated system for the electrogenic excretion of acetate in Desulfovibrio desulfurecans; and (3) development of a method to p...
Clinical data indicate a link of disease progression and resistance to imatinib therapy. While previous work on imatininb resistance has focused on mutations in the drug target these cannot explain the reduced effectiveness of imatinib in advanced disease...
The overall goal of this project is to test the hypothesis that the action of growth factors on mammary neoplasia and tumor progression is mediated, at least in part, by their action on the genes for matrix-degrading metalloproteinases (MMPs). This hypoth...
This progress report highlights our past 12 months of work on understanding neuroendocrine differentiation in prostate cancer (CaP). We have made headway into understanding the paracrine relationship between neuropeptide expressing CaP cells and androgen-...
We explored the relationship between androgen withdrawal as an event that initiates a cascade promoting the development of androgen-independent prostate cancer through neuroendocrine progression. We define the early post- castration molecular events and l...
Progression of prostate cancer (PCa) from hormone-dependent to hormone-refractory state represents one of the major hurdles in the successful treatment of cancer patients. Early studies showed that nearly all cancers retain androgen receptor (AR) -mediate...
We previously reported that adenosine, through A(2A) receptor activation, potentiates synaptic actions of brain-derived neurotrophic factor (BDNF) in the hippocampus of infant (3-4 weeks) rats. Since A(2A)-receptor-mediated actions are more evident in old than in young rats and since the ...
When plasma levels of homocysteine (HC), a thiol amino acid formed upon methionine demethylation, exceed 12 ?M, individuals are at increased risk of developing large vessel atherothrombosis and small vessel dysfunction. The annexin A2 complex (termed �A2�) is the cell surface coreceptor for plasminogen and TPA ...
The present study was performed to investigate the effect of flavonols, namely myricetin and structurally related quercetin and kaempferol against A2E and blue light-induced photoreceptors death in primary retinal cell cultures. Primary retinal cell cultures were prepared from bovine retinas. Fourteen-day-old cultures were pretreated with different ...
Studies show that kidneys produce 2',3'-cAMP, 2',3'-cAMP is exported and metabolized to 2'-AMP and 3'-AMP, 2'-AMP and 3'-AMP are metabolized to adenosine, 2',3'-cAMP inhibits proliferation of preglomerular vascular smooth muscle cells (PGVSMCs) and glomerular mesangial cells (GMCs), and A(2B) (not A(1), A(2A), or A(3)) adenosine receptors ...
PGs and other eicosanoids exert important physiological actions in insects and other invertebrates, including influencing ion transport and mediating cellular immune defense functions. Although these actions are very well documented, we have no information on the mechanisms PGs action in insect cel...
In this study, we report the effect of dimethyl sulfoxide (DMSO), acetonitrile, and methanol on the cytochrome P4501A2 (CYP1A2) mediated metabolism of phenacetin in human liver microsomes (HLM). Phenacetin O-deethylation is the preferred probe reaction for CYP1A2 where the metabolite, ...
nitrogen. For the experiments involving deuterium substitution, mediators, reductant, and oxidant were.45, A2 = 0.55, and A3 = 0.5 mT), identified by 2Hsubstitution. Incubation of oxidized formate of the oxidized native enzyme resulted in a shift of the Mo(V) EPR signal to higher field (g, = 2.005, g2= 1
Adenosine is an important paracrine agent regulating renal vascular tone via adenosine A(1) and A(2) receptors. While A(2B) receptor message and protein have been localized to preglomerular vessels, functional evidence on the role of A(2B) receptors in mediating the vasodilator action of adenosine on afferent arterioles is not ...
BackgroundHepatocellular carcinoma (HCC) is one of the world's leading causes of death among cancer patients. It is important to find a new biomarker that diagnoses HCC and monitors its treatment. In our previous work, we screened a single-chain antibody (scFv) N14, which could specifically recognize human HepG2 HCC cells but not human non-cancerous liver LO2 cells. However, the antigen it ...
Mutations in ATP13A2 (PARK9) have been linked to juvenile parkinsonism with dementia or Kufor-Rakeb syndrome (KRS). The ATP13A2 gene encodes at least three protein isoforms that arise by alternate splicing. A previous study indicated the Atp13a2(Isoform-1) protein is localized to lysosomes, whereas three separate mutations involved in disease cause retention of the protein in the ER. One ...
Mucociliary clearance, vital to lung clearance, is dependent on cilia beat frequency (CBF), coordination of cilia, and the maintenance of periciliary fluid. Adenosine, the metabolic breakdown product of ATP, is an important modulator of ciliary motility. However, the contributions of specific adenosine receptors to key airway ciliary motility processes are unclear. We hypothesized that adenosine ...
Transforming growth factor (TGF)-? is a central mediator in the progression of glomerulosclerosis, leading to accumulation of aberrant extracellular matrix proteins and inappropriate expression of smooth muscle ?-actin in the kidney. Previously, we reported that disrupting the cytoskeleton diminished TGF-?-stimulated type I collagen accumulation in human ...
Context:P450 oxidoreductase (POR) is a crucial electron donor to all microsomal P450 cytochrome (CYP) enzymes including 17?-hydroxylase (CYP17A1), 21-hydroxylase (CYP21A2) and P450 aromatase. Mutant POR causes congenital adrenal hyperplasia with combined glucocorticoid and sex steroid deficiency. P450 oxidoreductase deficiency (ORD) commonly presents ...
Interleukin-8 (IL8/CXCL8) has been described as a key effector in prostate cancer progression and resistance to standard chemotherapeutic drugs. In the present study, we investigated the effect of the natural, angio-inhibitory and anti-tumoral Pigment Epithelium-Derived Factor (PEDF) on the expression of IL8 cytokine by prostate cancer cells. Using a cytokine antibody array ...
We describe the receptor binding and antagonistic properties of two novel nonpeptide antagonists, FR167344 (3-bromo-8-[2,6-dichloro-3-[N-[(E)-4-(N,N-dimethylcarbamoyl)cinnamido acetyl]-N-methylamino]benzyloxy]-2-methylimidazo[1,2-a]pyridine hydrochloride) and FR173657 (8-[3-[N-[(E)-3-(6-acetamidopyridin-3-yl)acryloylglycyl]-N-m ethylamino]-2,6-dichlorobenzyloxy]-2-methylquinoline), for the human ...
1. Background: Bone marrow engraftment is mediated by stem cells with complex self-renewal, proliferative and differentiation potentials. This process is empirically documented by the progressive rise in the absolute neutrophil count occurring 2 to 3 weeks post-marrow infusion. 2. Purpose: To investigate the kinetics of early engraftment using in situ ...
Oxidative stress and inflammation are important processes in the progression of Alzheimer's disease (AD). Recent studies have implicated the role of amyloid ?-peptides (A?) in mediating these processes. In astrocytes, oligomeric A? induces the assembly of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complexes resulting in its activation to ...
Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). ...
The MVLN cell line was established in our laboratory from MCF-7 cells by stable transfection with the luciferase gene under the control of an estrogen-responsive element from the Xenopus vitellogenin A2 gene. This cell line allowed us to visualize the induction by hydroxytamoxifen of a heterogeneity in the cell population with regard to the expression of ...
Hepatitis B virus splice-generated protein (HBSP), encoded by a spliced hepatitis B virus RNA, was recently identified in liver biopsy specimens from patients with chronic active hepatitis B. We investigated the possible generation of immunogenic peptides by the processing of this protein in vivo. We identified a panel of potential epitopes in HBSP by using predictive computational algorithms for ...
Background: Cancer-associated thrombosis and enduring inflammation are strongly associated with cancer progression and metastasis. Heparin, is the mostly clinically used anticoagulant/antithrombotic drug, which has recently been shown to exhibit antimetastatic and antiinflammatory activities that are linked to inhibition of P- and/or L-selectin. ...
The renin-angiotensin-aldosterone-system (RAAS) is an important regulator of blood pressure and fluid-electrolyte homeostasis. RAAS has been implicated in pathogenesis of hypertension, congestive heart failure, and chronic renal failure. Aliskiren is the first non-peptide orally active renin inhibitor approved by FDA. Angiotensin Converting Enzyme (ACE) Inhibitors are associated with frequent side ...
Enhanced transforming growth factor-?1 (TGF-?1) expression in renal cells promotes fibrosis and hypertrophy during the progression of diabetic nephropathy. The TGF-?1 promoter is positively controlled by the E-box regulators, upstream stimulatory factors (USFs), in response to diabetic (high glucose) conditions; however, it is not clear whether TGF-?1 is autoregulated by ...
Ubiquitin-mediated proteolysis of cyclins, cyclin-dependent kinase inhibitors and certain other substrates, including proteins whose degradation is necessary for progression through mitosis, provide a molecular basis for unidirectional progression through...
This report describes progress aimed at constructing gene-transfer technology for Nicotiana plumbaginifolia. Most actual effort as described herein has so far been directed at exploring new perspectives and limitations in Agrobacterium mediated gene transfer. Accomplishments are described using a core homologous gene targeting vector.
This report describes progress aimed at constructing gene-transfer technology for Nicotiana plumbaginifolia. Most actual effort as described herein has so far been directed at exploring new perspectives and limitations in Agrobacterium mediated gene trans...
The process of alternative splicing is widely misregulated in cancer, but the contribution of splicing regulators to cancer development is largely unknown. In this study, we found that the splicing factor hnRNP A2/B1 is overexpressed in glioblastomas and is correlated with poor prognosis. Conversely, patients who harbor deletions of the HNRNPA2B1 gene show ...
The anti-inflammatory properties of soyasaponins (especially soyasaponins with different chemical structures) have scarcely been investigated. We investigated the inhibitory effects of five structural types of soyasaponins (soyasaponin A(1), A(2), I and soyasapogenol A, B) on the induction of nitric oxide (NO) and inducible NO synthase (iNOS) in murine RAW ...
BackgroundMembers of the TRIP-Br/SERTAD family of mammalian transcriptional coregulators have recently been implicated in E2F-mediated cell cycle progression and tumorigenesis. We, herein, focus on the detailed functional characterization of the least understood member of the TRIP-Br/SERTAD protein family, TRIP-Br2 (SERTAD2).MethodsOncogenic potential of ...
Cerebral ischemia�reperfusion (I/R) insults result in neuronal cell death, brain tissue loss, and severe neurological deficits. However, the underlying mechanism is still not fully understood. Heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 belongs to a family of RNA-binding proteins that plays a central role in pre-mRNA processing. Recent studies ...
Recent studies indicate that phospholipase A2 (PLA2) derived lipid mediators regulate a number of neutrophil responses such as chemotaxis, adhesion and degranulation. Since tumor necrosis factor (TNF) is also a key mediator in neutrophil activation, it remains to be shown that PLA2 is involved in the process of TNF ...
The SmI(2)-mediated radical coupling reactions of ?-hydroxylated pyrrolidine/piperidine aza-hemiacetals 8 and 9 and N,S-acetals 6 and 33 with ?,?-unsaturated compounds are described. This method allows a rapid access to ?-hydroxylated pyrrolidines, piperidines, pyrrolizidinones, and indolizidinones. Starting from N,S-acetal 33 and via a common intermediate 27, the alkaloids ...
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder associated with fragile X premutation carriers. Previous studies have shown that fragile X rCGG repeats are sufficient to cause neurodegeneration and that the rCGG repeat-binding proteins Pur ? and hnRNP A2/B1 could modulate rCGG-mediated neuronal ...
2A is an oligopeptide sequence mediating a ribosome �skipping� effect, producing an apparent �cleavage� of polyproteins. First identified and characterized in picornaviruses, �2A-like� sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst ...
Background:Solute carriers (SLCs), in particular organic cation transporters (OCTs), have been implicated in the cellular uptake of platinum-containing anticancer compounds. The activity of these carriers may determine the pharmacokinetics and the severity of side effects, including neuro- and nephrotoxicity of platinum-based chemotherapy. As decreased drug accumulation is a key mechanism of ...
The overall objective of this proposal is to enable Iowa State University to establish a Center that enjoys world-class stature and eventually enhances the economy through the transfer of innovation from the laboratory to the marketplace. The funds have been used to support experimental proposals from interdisciplinary research teams in areas related to catalysis and green chemistry. Specific ...
Parkinson's Disease (PD) and Extrapyramidal Syndrome (EPS) are movement disorders that result from degeneration of the dopaminergic input to the striatum and chronic inhibition of striatal dopamine D(2) receptors by antipsychotics, respectively. Adenosine A(2A) receptors are selectively localized in the basal ganglia, primarily in the striatopallidal ...
Human CYP1A2 is one of the major CYPs in human liver and metabolizes a variety of clinically important drugs (e.g., clozapine, tacrine, tizanidine, and theophylline), a number of procarcinogens (e.g. benzo[a]pyrene and aflatoxin B(1)), and several important endogenous compounds (e.g. steroids and arachidonic acids). Like many of other CYPs, ...
Human CYP1A2 is one of the major CYPs in human liver and metabolizes a variety of clinically important drugs (e.g., clozapine, tacrine, tizanidine, and theophylline), a number of procarcinogens (e.g. benzo[a]pyrene and aflatoxin B1), and several important endogenous compounds (e.g. steroids and arachidonic acids). Like many of other ...
Background and PurposeCerebral venous thrombosis (CVT) may be a manifestation of underlying autoimmune disease. Antibodies against annexin A2 (anti-A2Ab) coincide with the antiphospholipid syndrome (APS), in which antiphospholipid antibodies (aPLA) are associated with thrombosis in any vascular bed. Annexin ...
Adenosine receptors are G protein-coupled receptors (GPCRs) that mediate the physiological functions of adenosine. In the central nervous system adenosine A2A receptors (A2ARs) are highly enriched in striatopallidal neurons where they form functional oligomeric complexes with other GPCRs such ...
In neuroendocrine cells, annexin-A2 is implicated as a promoter of monosialotetrahexosylganglioside (GM1)-containing lipid microdomains that are required for calcium-regulated exocytosis. As soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) require a specific lipid environment to mediate granule docking ...
Background and purposeAdenosine, an endogenous purine nucleoside, is a potent regulator of the inflammatory response and stimulus for fibrosis. We have previously demonstrated that adenosine, acting at the A2A receptor, plays a central role in hepatic fibrosis via direct promotion of collagen production by hepatic stellate cells. As we have previously demonstrated that macrophage ...
The production of adenosine represents a critical endogenous mechanism for regulating immune and inflammatory responses during conditions of stress, injury, or infection. Adenosine exerts predominantly protective effects through activation of four 7-transmembrane receptor subtypes termed A1, A2A, A2B, and A3, of ...
This study evaluated the ability of two new, selective antagonists of the gamma-aminobutyric acidB (GABAB) receptor, phaclofen (PHAC) and 2-hydroxy-saclofen (2-OH-S), to antagonize the increase in tail-flick latency (TFL) and hot-plate latency (HPL) produced by i.t. administered baclofen (BAC) in the rat. The putative GABAB receptor antagonist delta-aminovaleric acid (DAVA) was also examined for ...
The mechanisms of calicivirus attachment and internalization are not well understood, mainly due to the lack of a reliable cell-culture system for most of its members. In this study, rabbit vesivirus (RaV) virions were shown to bind annexin A2 (ANXA2) in a membrane protein fraction from HEK293T cells, using a virus overlay protein-binding assay and ...
Von Willebrand factor (VWF) is secreted as ultralarge multimers that are cleaved in the A2 domain by the metalloprotease ADAMTS13 to give smaller multimers. Cleaved VWF is activated by hydrodynamic forces found in arteriolar bleeding to promote hemostasis, whereas uncleaved VWF is activated at lower, physiologic shear stresses and causes thrombosis. Single-molecule experiments demonstrate that ...