Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To determine the effects of food deprivation on the physical, physiological, and metabolic responses to exercise in the heat, adult, male rats (330-360g, N = 16/group) were food-deprived for 24, 48, or 72 h. They were then exercised (9.14m X min-1) in the heat (35.5 degrees C) to hyperthermic exhaustion (Tco approximately 43 degrees C). Food deprivation had no effects on endurance, but ad lib fed controls manifested significantly (p less than 0.05) increased Tco and Tsk during the latter portion of the treadmill interval. While plasma osmolality was significantly (p less than 0.01) increased in all groups as a result of the heat/exercise contingency, hematocrit ratios were elevated (p less than 0.01) as a result of 48 and 72 h of food deprivation. Food deprivation resulted in severe hypoglycemia following exercise (p less than 0.01), and these decrements were accompanied by marked (p less than 0.01) reductions in circulating insulin levels. Prolonged food deprivation (48 and 72 h) resulted in significant (p less than 0.01) hypertriglyceridemia and hyperlactacidemia subsequent to exercise. Levels of sodium, potassium, urea nitrogen, and creatine phosphokinase were unaffected by the food deprivation intervals. We have concluded from these studies that while several thermoregulatory and metabolic responses to exercise in the heat can be significantly affected by food deprivation, short-term endurance capacity was unaltered.
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PMID:Food deprivation and exercise in the heat: thermoregulatory and metabolic effects. 389 96

To determine the effects of low-dosage organophosphate administration on exercise in a hot environment, malathion (7.5 mg/day, 4 days) was administered IP to rats, and effected a 35% (p less than 0.01) reduction in plasma cholinesterase levels. Treadmill endurance (9.14 m/min, no incline, 35 degrees C ambient) was unaffected when the animals were exercised to hyperthermic exhaustion (Tre approximately 43 degrees C). While rates of heat gain were similar between groups, malathion-treated rats displayed higher Tsk (p less than 0.05) at a number of sampling times during the treadmill run. While creatine phosphokinase levels were unaffected by either cholinesterase inhibition or exercise in the heat, lactate dehydrogenase activities were increased (p less than 0.01) in both groups following hyperthermic exhaustion. Although plasma levels of lactate, potassium, urea nitrogen, and creatinine were all significantly (p less than 0.01) increased as a result of exercise in the heat, these increments were not exacerbated by cholinesterase inhibition. Results generally indicated that at this moderate level cholinesterase inhibition, malathion administration did not adversely affect physiological, physical, or thermoregulatory efficacy.
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PMID:Malathion administration: effects on physiological and physical performance in the heat. 665 21

Dystrophin-deficient female mdx mice were bred with male Tsk+/+ pa mice to examine the role played by mast cells in the pathophysiology of dystrophin deficiency. Resultant mdx/Tsk double-mutant mice were then examined functionally, biochemically, and histologically. While mdx mice remained as strong as their normal counterparts, mdx/Tsk double-mutant mice became progressively weak with age. Serum creatine kinase activity was significantly elevated in both mdx and mdx/Tsk double-mutant mice over normal controls. However, mast cell-derived plasma tryptase activity was consistently higher in the double-mutant than in mdx mice. In addition, histological examination of gastrocnemius muscle revealed that while necrosis was persistent in both strains of mdx mice from 2 to 8 weeks of age, regeneration was significantly reduced in the double-mutant mice. Of particular interest was the fact that necrosis in the mdx/Tsk double mutant exceeded mdx values at 8 weeks of age, corresponding approximately with a second peak in tryptase activity. Therefore, heightened mast cell activity appears to elicit in the dystrophin-deficient mdx mouse a myopathy not unlike the human Duchenne disease.
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PMID:Duchenne-like myopathy in double-mutant mdx mice expressing exaggerated mast cell activity. 756 39

Transcription of specific skeletal muscle genes requires the expression of the muscle regulatory factor myogenin. To assess the role of the extracellular matrix (ECM) in skeletal muscle differentiation, the specific inhibitors of proteoglycan synthesis, sodium chlorate and beta-D-xyloside, were used. Treatment of cultured skeletal muscle cells with each inhibitor substantially abolished the expression of creatine kinase and alpha-dystroglycan. This inhibition was totally reversed by the addition of exogenous ECM. Myoblast treatment with each inhibitor affected the deposition and assembly of the ECM constituents glypican, fibronectin, and laminin. These treatments did not affect MyoD, MEF2A, and myogenin expression and nuclear localization. Differentiated myoblast treatment with RGDS peptides completely inhibited myogenesis without affecting the expression or nuclear localization of myogenin. Integrin-mediated signaling of focal adhesion kinase was partially inhibited by chlorate and beta-D-xyloside, an effect reversed by the addition of exogenous ECM gel. These results suggested that the expression of myogenin is not sufficient to successfully drive skeletal muscle formation and that ECM is required to complete the skeletal muscle differentiation process.
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PMID:ECM is required for skeletal muscle differentiation independently of muscle regulatory factor expression. 1178 50

Previous reports suggest that PKC plays an important role in regulating myogenesis. However, the regulatory signaling pathways are not fully understood. We examined the effects of PKC downregulation on signaling events during skeletal muscle differentiation. We found that downregulation of PKC results in increased myogenesis in C2C12 cells as measured by creatine kinase activity and myogenin expression. We showed that, during differentiation, downregulation of PKC expression results in increased tyrosine phosphorylation of FAK, Cas, and paxillin, concomitant with enhanced Cas-CrkII complex formation, which leads to activation of JNK2. But in proliferated muscle cells, PKC inhibition results in FAK and Cas tyrosine dephosphorylation. Further, disruption of actin cytoskeleton by cytochalasin D prevents the activation of FAK and Cas as well as the formation of Cas-CrkII complex stimulated by PKC downregulation during muscle cell differentiation. Finally, we observed that PKC downregulation increases the tyrosine phosphorylation of focal adhesion associated proteins. Based on the above data, we propose that PKC downregulation results in enhanced tyrosine phosphorylation of FAK, Cas, and paxillin, thus promoting the establishment of Cas-CrkII complex, leading to activation of JNK and that these interactions are dependent upon the integrity of actin cytoskeleton during muscle cell differentiation. Data presented here significantly contribute to elucidating the regulatory role of PKC in myogenesis possibly through integrin signaling pathway.
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PMID:PKC-regulated myogenesis is associated with increased tyrosine phosphorylation of FAK, Cas, and paxillin, formation of Cas-CRK complex, and JNK activation. 1219 Sep 87

We previously isolated and characterized the novel human gene MOST-1 (C8orf17) that is ubiquitously expressed in all cancer cell lines tested but differentially expressed in normal adult tissues. MOST-1 maps to chromosome region 8q24.2 whose amplification is frequently associated with breast and prostate cancers. RT-PCR analyses of breast and prostatic biopsies revealed MOST-1 overexpression and/or amplification in high-grade carcinomas. We raised and characterized a polyclonal antibody against a MOST-1-specific synthetic peptide. in vitro expression of MOST-1 protein revealed a tendency to exist as high molecular mass isoforms which are SDS-insoluble upon thermal stress. MOST-1 displayed cytoplasmic localization in four human cell lines (hTERT-HME1 normal mammary epithelial, MCF7 breast adenocarcinoma, PrEC normal prostate epithelial and DU145 prostate carcinoma), with polar expression during cell division. Knockdown of MOST-1 expression in DU145 cells resulted in reduced cell proliferation but enhanced apoptosis implying a putative mitogenic role of MOST-1. Yeast two-hybrid analyses demonstrated interaction with seven human proteins, most of which are overexpressed in tumors or involved in metabolic pathways. The interacting proteins were creatine kinase, Gardner feline sarcoma v-FGR oncogene product, telethonin, SNC73 protein, ferritin light chain, peripheral benzodiazepine receptor, and immunoglobulin C (mu) and C (delta) heavy chain. Co-immunoprecipitation assays validated the interactions of MOST-1 with the latter three proteins. Our results suggest that MOST-1 is associated with cell survival, proliferation and progression of cancer cells.
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PMID:Cellular expression, localization and interactions of the product of the human MOST-1 gene associated with breast and prostate cancers. 1714 15

The purpose of this evaluation was to perform a method comparison of the assays for cardiac troponin I (cTnl), CK-MB, myoglobin, and NT-proBNP on the automated PATHFAST Immuno-Assay Analyzer with respective immunoassays on other commercially available immunoanalyzers. The PATHFAST assays are immunochemiluminescent assays (in single reagent cartridges) employing two mono- or polyclonal antibodies in a sandwich test format. The calibration materials for cTnI and CK-MB are standardized to the reference materials NIST SRM 2921 (troponin CIT complex) and IRMM-IFCC 455 (CK-MB mass). The PATHFAST assays for cTnI, CK-MB, myoglobin, and NT-proBNP on the PATHFAST Analyzer were compared using 118 (NT-proBNP: 90) plasma samples from patients with different cardiovascular diseases with those on the Dade Behring StratusCS Analyzer, on the Abbott AxSYM System, on the DPC IMMMULITE 2000 Analyzer, on the Biosite Triage Meter Plus System, on the Roche Elecsys Immuno Analyzer 2010 and Roche Cardiac Reader System, respectively. The correlation coefficients for the comparison of cTnI methods ranged from 0.953 to 0.982, those for the comparison of myoglobin methods ranged from 0.776 to 0.992, and those for the comparison of CK-MB methods ranged from 0.835 to 0.999, with the Triage System giving in all comparisons the lowest correlation. Also the comparison of PATHFAST NTproBNP against the Roche Elecsys assay yielded a very good correlation (r = 0.992). The slopes of the regression line among methods showed considerable variation indicating that standardization efforts by international groups are indispensable to achieve harmonization of results. In summary, this evaluation study confirms the overall good correlation of the results obtained with assays for cardiac markers developed on the PATHFAST analyzer with those on other immunoassay platforms and thus the analytical reliability of the developed methods.
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PMID:Method comparison of cardiac marker assays on PATHFAST, StratusCS, AxSYM, Immulite 2000, triage, elecsys and cardiac reader. 1717 92

Hyper-transaminasemia (HT) is a well-known laboratory sign of celiac disease (CD); however, hyper-creatine phosphokinase (CK)-emia (HCK) is not so familiar. As there are reported cases of myopathy associated CD in the literature, we aimed to investigate serum CK levels of children with CD. Newly diagnosed 126 children were included. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and CK levels were determined. Mean age was 8.7+/-4.4 years (11 mo to 18 y). Of patients, 77 (61.1%) had classic form, 49 (38.9%) had atypical form. Elevated levels of AST, ALT, and CK, respectively, were found in 65 (51.6%), 45 (35.7%), and 50 (39.7%) patients. Isolated HCK was detected in 9 (7.1%) patients. AST, ALT, and CK were all elevated in 29 (23.0%) children. Mean serum AST, ALT, and CK levels were found as 56.1+/-53.7 U/L (11 to 403), 44.7+/-44.0 U/L (7 to 290), and 258.0+/-686.5 U/L (36 to 5956), respectively. In 95 (75.4%) children, AST/ALT value was greater than 1, and in 19 (15.1%) it was greater than 2. We found positive correlations with the level of CK and AST, and ALT (P=0.01). CK level was inversely correlated with hemoglobin and cholesterol levels (P=0.013 and 0.007). In conclusion, this is the first study, which determined elevated serum levels of CK in CD and demonstrated that HCK is as common as HT in children with CD. We emphasize that HT seen in CD is not necessarily a sign of liver injury, but may also be due to myopathy.
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PMID:Hyper-CK-emia in pediatric celiac disease: prevalence and clinical importance. 1766 50

EPO (erythropoietin) has recently been shown to have protective actions upon the myocardium; however, the direct effects of EPO upon cardiac contractile and secretory functions are unknown and the signalling mechanisms are not well defined. In the present study, we provide the first evidence of direct cardiac contractile actions of EPO. In isolated perfused Sprague-Dawley rat hearts, a 30 min infusion of EPO significantly increased contractility in a dose-dependent fashion (maximal change 18+/-2% with 1 unit/ml EPO; P<0.005 compared with vehicle). Perfusate ET-1 (endothelin-1) increased transiently during EPO infusion, and the ET(A/)ET(B) antagonist bosentan abolished the inotropic response to EPO. BNP (B-type natriuretic peptide) secretion (28+/-8%; P<0.05) and nuclear transcription factor GATA-4 DNA-binding activity (51%; P<0.05) were both significantly increased by EPO and blocked by bosentan. In a model of global ischaemic injury, delivery of 1 unit/ml EPO during reperfusion significantly attenuated creatine kinase release (28+/-12%; P<0.05) and significantly improved contractile recovery (P<0.001), independent of ET(A) blockade. Apoptotic indices [assessed by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling)/cleaved caspase-3-positive cells] were significantly decreased (P<0.01) by 1 unit/ml EPO during reperfusion alone, coincident with significantly increased phosphorylation of myocardial JAK2 (Janus kinase 2) and STAT3 (signal transducer and activator of transcription 3). Thus EPO directly enhances cardiac contractility and BNP secretion and alleviates ischemia/reperfusion injury via ET-1-dependent and -independent mechanisms respectively.
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PMID:Direct cardiac actions of erythropoietin (EPO): effects on cardiac contractility, BNP secretion and ischaemia/reperfusion injury. 1791 23

We evaluated the cardioprotection against myocardial ischemia-reperfusion injury induced by sevoflurane postconditioning (SpostC) in chronically-infarcted rat hearts, and investigated the roles of phosphoinositide 3-kinase (PI3K)-protein kinase B/Akt (PKB/Akt), mitogen-activated extracellular regulated kinase 1/2 (MEK 1/2)-extracellular regulated kinase 1/2 (ERK 1/2), and mitochondrial permeability transition pore (mPTP). Left anterior descending (LAD) coronary artery was ligated to induce myocardial infarction in rats. Six weeks later, chronically-infarcted hearts were isolated and subjected to 30 min of global ischemia, followed by 1 h of reperfusion with Krebs-Henseleit (K-H) buffer. SpostC was administered by perfusing the hearts with K-H buffer saturated with 3% sevoflurane during the first 15 min of reperfusion. To evaluate the role of PI3K-PKB/Akt and MEK 1/2-ERK 1/2 in SpostC, PI3K inhibitor LY294002 (15 microM) and MEK 1/2 inhibitor PD98059 (20 microM) were administered alone or together with sevoflurane during the first 15 min of reperfusion. We found that exposure of 3% sevoflurane during early reperfusion significantly improved functional recovery (improved left ventricular developed pressure (LVDP), +/-dp/dt, CF, HR and reduced left ventricular end-diastolic pressure (LVEDP)), decreased myocardial infarct size and reduced LDH and CK-MB release, when compared with unprotected hearts. However, these protective effects were abolished in the presence of either LY294002 or PD98059, which was accompanied by the prevention of PKB/Akt and ERK 1/2 phosphorylation, and reduction of myocardial nicotinamide adenine dinucleotide (NAD+) content. These findings suggest that sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by inhibiting mPTP opening via recruitment of PKB/Akt and ERK 1/2.
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PMID:Sevoflurane postconditioning protects chronically-infarcted rat hearts against ischemia-reperfusion injury by activation of pro-survival kinases and inhibition of mitochondrial permeability transition pore opening upon reperfusion. 1988 Dec 97


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