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Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery. Free Radic Biol Med 2008 Feb 15;44(4):518-26

Date

11/13/2007

Pubmed ID

17997382

DOI

10.1016/j.freeradbiomed.2007.10.040

Scopus ID

2-s2.0-38649127552   27 Citations

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-alpha 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.

Author List

Maenpaa CJ, Shames BD, Van Why SK, Johnson CP, Nilakantan V

Authors

Christopher P. Johnson MD Professor in the Surgery department at Medical College of Wisconsin
Scott K. Van Why MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Adenosine Triphosphate
Animals
Apoptosis
Cells, Cultured
Epithelial Cells
Kidney
Kidney Tubules, Proximal
Metalloporphyrins
Oxidants
Proto-Oncogene Proteins c-bcl-2
Reactive Oxygen Species
Reperfusion Injury
Swine
Tumor Necrosis Factor-alpha
jenkins-FCD Prod-478 d1509cf07a111124a2d122fd3df854cc0b993c00