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- W2063375483 abstract "Oxidant-mediated apoptosis has been implicated in renal injury due to ischemia reperfusion (IR); however, the apoptotic signaling pathways following IR have been incompletely defined. The purpose of this study was to examine the role of oxidants on cell death in a model of in vitro simulated IR injury in renal proximal tubular epithelial cells by analyzing the effects of a cell-permeable superoxide dismutase mimetic, manganese (III) tetrakis (1-methyl-4-pyridyl) porphyrin pentachloride (MnTmPyP). Renal proximal tubular epithelial cells were ATP depleted for 2, 4, or 6 h, followed by 2 h of recovery. We found that MnTmPyP was effective in attenuating cytotoxicity (P < 0.001) and decreasing steady-state oxidant levels (P < 0.001) and apoptotic cell death (P < 0.001) following ATP depletion-recovery. MnTmPyP treatment prevented the early cytosolic release of cytochrome c and increased Bcl-2 protein levels following short durations of ATP depletion-recovery. After longer periods of ATP depletion-recovery, we observed a significant increase in TNF-α protein levels (P < 0.001) and caspase-8 activation (P < 0.001), both of which were decreased (P < 0.001) by treatment with MnTmPyP. Our results suggest that oxidant mediated apoptosis via the mitochondrial pathway during the early phase of ATP depletion and by activation of the receptor-mediated apoptotic pathway following longer durations of injury." @default.
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- W2063375483 date "2008-02-01" @default.
- W2063375483 modified "2023-09-26" @default.
- W2063375483 title "Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery" @default.
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- W2063375483 doi "https://doi.org/10.1016/j.freeradbiomed.2007.10.040" @default.
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