Cross-talk between nitric oxide and superoxide determines ceramide formation and apoptosis in glomerular cells.

摘要: Cross-talk between nitric oxide and superoxide determines ceramide formation apoptosis in glomerular cells. Background The modulation of cell signaling by (NO) (O 2 - ) is associated with apoptotic death inflammatory kidney diseases. Recently, we have shown that NO induces production mesangial endothelial cells the ratio O whether live or die. Methods Glomerular were labeled [ 14 C]serine, precursor all sphingolipids, then stimulated reactive oxygen species- nitrogen species-generating substances subjected to lipid extraction. Radioactive lipids separated analyzed thin-layer chromatography. DNA fragmentation, as a characteristic feature apoptosis, was measured nucleosome/DNA-ELISA, which quantitatively recorded histone-associated fragments. Results Exposure either donors superoxide-generating led delayed sustained paralleled induction both types. Coincubation superoxide, generation peroxynitrite, caused synergistic enhancement when compared stimulus alone. By contrast, costimulation neutralized not only NO-induced but also formation, although alone triggered death. Moreover, SIN-1, substance simultaneously releases thereby generates Furthermore, exposure glucose oxidase, hydrogen peroxide, exogenous showed dose-dependent increase lesser extent than did superoxide. Conclusions These data suggest represents an important mediator species-triggered responses, like apoptosis. There seem be type-specific protective mechanisms critically depend on fine-tuned redox balance species determine undergoes survives exposed oxidative and/or nitrosative stress conditions.