Oxidative and nitrosative stress in kidney disease: a case for cyclosporine A.
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.
Redondo-Horcajo
M
M
Centro de Investigaciones Biologicas (CIB, CSIC), Instituto "Reina Sofia" de Investigaciones Nefrologicas (IRSIN) and Fundacion Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), Madrid - Spain.
Lamas
S
S
D016572:Cyclosporine / Q000494:pharmacology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007674:Kidney Diseases / Q000188:drug therapy / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D007166:Immunosuppressive Agents; D016572:Cyclosporine