摘要 : We have previously shown that in vivo renal ischemia/reperfusion results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. Current Studies were designed to compare the effect of ATP dep... 展开 We have previously shown that in vivo renal ischemia/reperfusion results in ATP depletion, oxidant production, and manganese superoxide dismutase (MnSOD) inactivation. Current Studies were designed to compare the effect of ATP depletion (Antimycin A treatment) on cell death pathways using renal proximal tubular cells and identical cells that overexpress MnSOD. ATP depletion in wild-type cells induced an apoptotic cascade that involved caspase 9 activation; MnSOD overexpressing cells afforded protection against apoptosis. This protection did not appear to involve a cytochrome e-related mechanism, but may be related to altered levels of nitric oxide within the cell. Further studies suggested that nitric oxide was required to protect the renal cells from caspase-rnediated cell death. Interestingly, treatment of renal cell extracts with reductants (DTT and ascorbate) enhanced caspase activation. Taken together, these results suggest that cysteine nitrosylation may be playing a role in caspase dysfunction in cells overexpressing MnSOD following ATP depletion. (c) 2005 Elsevier Inc. All rights reserved. 收起