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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.FR

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.

Authors+Show Affiliations

Division of Transplant Surgery, Medical College of Wisconsin, Milwaukee, WI 53226, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17997382

Citation

Maenpaa, Cheryl J., et al. "Oxidant-mediated Apoptosis in Proximal Tubular Epithelial Cells Following ATP Depletion and Recovery." Free Radical Biology & Medicine, vol. 44, no. 4, 2008, pp. 518-26.
Maenpaa CJ, Shames BD, Van Why SK, et al. Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery. Free Radic Biol Med. 2008;44(4):518-26.
Maenpaa, C. J., Shames, B. D., Van Why, S. K., Johnson, C. P., & Nilakantan, V. (2008). Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery. Free Radical Biology & Medicine, 44(4), 518-26.
Maenpaa CJ, et al. Oxidant-mediated Apoptosis in Proximal Tubular Epithelial Cells Following ATP Depletion and Recovery. Free Radic Biol Med. 2008 Feb 15;44(4):518-26. PubMed PMID: 17997382.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidant-mediated apoptosis in proximal tubular epithelial cells following ATP depletion and recovery. AU - Maenpaa,Cheryl J, AU - Shames,Brian D, AU - Van Why,Scott K, AU - Johnson,Christopher P, AU - Nilakantan,Vani, Y1 - 2007/10/26/ PY - 2007/06/29/received PY - 2007/10/08/revised PY - 2007/10/08/accepted PY - 2007/11/13/pubmed PY - 2008/3/7/medline PY - 2007/11/13/entrez SP - 518 EP - 26 JF - Free radical biology & medicine JO - Free Radic Biol Med VL - 44 IS - 4 N2 - 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. SN - 0891-5849 UR - https://www.unboundmedicine.com/medline/citation/17997382/Oxidant_mediated_apoptosis_in_proximal_tubular_epithelial_cells_following_ATP_depletion_and_recovery_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0891-5849(07)00679-X DB - PRIME DP - Unbound Medicine ER -