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  • Title: Overexpression of manganese superoxide dismutase protects against ATP depletion-mediated cell death of proximal tubule cells.
    Author: Cruthirds DL, Saba H, MacMillan-Crow LA.
    Journal: Arch Biochem Biophys; 2005 May 01; 437(1):96-105. PubMed ID: 15820221.
    Abstract:
    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 c-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-mediated 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.
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