Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:Q8IXL6 (RNS)
 1,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The immunosuppresor cyclosporine A (CsA) has been associated to human endothelial dysfunction and accelerated atherosclerosis. Sympathetic overactivity, relative deficiency of nitric oxide, TGFb-1, endothelin-1, reactive oxygen (ROS) and nitrogen species (RNS) and vasoconstrictor eicosanoids are mediators of vascular dysfunction associated to cyclosporine A. In CsA-treated cells (BAEC) an increase in reactive oxygen and nitrogen intermediates may lead to the intracellular formation of peroxynitrite. This agent could be one important mediator by which CsA produces an antioxidant-sensitive nitration of tyrosine, a marker for endothelial damage by nitrosative stress. Superoxide anion is the limiting factor in the formation of peroxynitrite in CsA-treated endothelial cells. Treatment with CsA may lead to the nitration of specific proteins such as manganese superoxide dismutase (MnSOD). We propose that peroxynitrite and tyrosine nitration may represent mechanisms of damage in pathophysiological situations where superoxide anion generation is increased.
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PMID:Oxidative and nitrosative stress in kidney disease: a case for cyclosporine A. 1624 54

We previously reported that hypoxia attenuates cGMP-dependent protein kinase (PKG)-mediated relaxation in pulmonary vessels (Am J Physiol Lung Cell Mol Physiol 279: L611-L618, 2003). To determine whether hypoxia-induced reactive oxygen and nitrogen species (ROS and RNS, respectively) may be involved in the downregulation of PKG-mediated relaxation, ovine fetal intrapulmonary veins were exposed to 4 h of normoxia or hypoxia, with or without scavengers of ROS [N-acetylcysteine (NAC)] or peroxynitrite (quercetin and Trolox) and preconstricted with endothelin-1. Hypoxia decreased the relaxation response to 8-bromo-cGMP, PKG protein expression, and kinase activity and increased tyrosine nitration in PKG. However, ROS and RNS scavengers prevented these changes. To determine whether increased PKG nitration diminishes PKG activity, pulmonary vein smooth muscle cells (PVSMC) were exposed to shorter-term (30 min) hypoxia, which increased PKG nitration and decreased PKG activity but did not alter PKG protein expression. Increased dihydro-2,7-dichlorofluorescein diacetate (DCFH(2)-DA) fluorescence in PVSMC after 4 h or 30 min of hypoxia was not observed in the presence of NAC, quercetin, or Trolox, suggesting increased ROS and RNS production. Increased PKG nitration and the associated decrease in PKG activity in PVSMC after 30 min of hypoxia were also reversed on reoxygenation. The consequences of PKG nitration were assessed by exposure of purified PKG-Ialpha to peroxynitrite, which caused increased 3-nitrotyrosine immunoreactivity and inhibition of kinase activity. Our data suggest that, after 30 min of hypoxia, reversible covalent modification of PKG by hypoxia-induced reactive species may be an important mechanism by which the relaxation response to cGMP is regulated. However, after 4 h of hypoxia, PKG nitration and decreased PKG expression are involved.
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PMID:Regulation of cGMP-dependent protein kinase-mediated vasodilation by hypoxia-induced reactive species in ovine fetal pulmonary veins. 1761 49