Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The endothelial EDRF/NO-mediated relaxing mechanism is impaired in atherosclerotic and in hypertensive arteries. Recently, it was suggested that primary pulmonary hypertension might be another disease in which the endothelial EDRF/NO pathway is disturbed. We tested the hypothesis that intravenous administration of L-arginine (L-ARG), the physiological precursor of EDRF/NO, stimulates the production of NO, subsequently increasing plasma cGMP levels and reducing systemic and/or pulmonary blood pressure, in patients with coronary artery disease (CAD, n = 16) or with primary pulmonary hypertension (PPH, n = 5). L-ARG (30 g, 150 ml, 15 min) or placebo (150 ml NaCl) was infused in CAD patients, and L-ARG was infused in PPH patients during cardiac catheterization. Mean aortic (Pao) and pulmonary (PAPmean) arterial pressures were continuously monitored. Cardiac output (CO, by thermodilution), total peripheral resistance (TPR), and pulmonary vascular resistance (PVR) were measured before and during the infusions. In CAD patients Pao decreased from 87.2 +/- 4.9 to 81.8 +/- 5.1 mmHg during L-ARG (p < 0.05), whereas PAPmean and PVR were unchanged. TPR decreased from 1008.9 +/- 87.9 to 845.0 +/- 81.7 dyne x sec x cm-5 during L-ARG administration (p < 0.01). CO significantly increased during L-ARG (from 7.3 +/- 2.8 to 8.1 +/- 0.9 l/min, p < 0.05). Placebo did not significantly influence any of the hemodynamic parameters. Plasma cGMP (determined by RIA) slightly increased by 12.2 +/- 9.6% during L-ARG, but slightly decreased during placebo (-12.3 +/- 9.2%) (p < 0.05 for L-ARG vs. placebo). In PPH patients, L-ARG induced no significant change in Pao, TPR, and CO, PAPmean was 59.4 +/- 8.5 mmHg at the beginning of the study and was not significantly reduced by L-ARG nor was PVR (basal: 1042.4 +/- 211.4 dyne x sec x cm-5) changed by L-ARG. Plasma cGMP was not significantly affected by L-ARG in these patients. We conclude that L-ARG stimulates NO production and induces vasorelaxation in CAD patients but not in patients with primary pulmonary hypertension.
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PMID:Differential systemic and pulmonary hemodynamic effects of L-arginine in patients with coronary artery disease or primary pulmonary hypertension. 886 93

During early embryogenesis in Caenorhabditis elegans, the ATL-1-CHK-1 (ataxia telangiectasia mutated and Rad3 related-Chk1) checkpoint controls the timing of cell division in the future germ line, or P lineage, of the animal. Activation of the CHK-1 pathway by its canonical stimulus DNA damage is actively suppressed in early embryos so that P lineage cell divisions may occur on schedule. We recently found that the rad-2 mutation alleviates this checkpoint silent DNA damage response and, by doing so, causes damage-dependent delays in early embryonic cell cycle progression and subsequent lethality. In this study, we report that mutations in the smk-1 gene cause the rad-2 phenotype. SMK-1 is a regulatory subunit of the PPH-4.1 (protein phosphatase 4) protein phosphatase, and we show that SMK-1 recruits PPH-4.1 to replicating chromatin, where it silences the CHK-1 response to DNA damage. These results identify the SMK-1-PPH-4.1 complex as a critical regulator of the CHK-1 pathway in a developmentally relevant context.
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PMID:SMK-1/PPH-4.1-mediated silencing of the CHK-1 response to DNA damage in early C. elegans embryos. 2058 18