Faculty Collaboration Database

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 (requires institutional sign-in at Scopus site)   28 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

Author

Christopher P. Johnson MD Professor in the Surgery 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