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dc.date.accessioned2018-06-11T08:46:51Z
dc.date.issued2010-05en_US
dc.identifier5en_US
dc.identifier.citationAMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2010, 298 pp. F1214 - F1221en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/1784
dc.description.abstractArany I, Faisal A, Clark JS, Vera T, Baliga R, Nagamine Y. p66SHC-mediated mitochondrial dysfunction in renal proximal tubule cells during oxidative injury. Am J Physiol Renal Physiol 298: F1214-F1221, 2010. First published January 6, 2010; doi:10.1152/ajprenal.00639.2009.-Mitochondrial dysfunction is involved in pathopysiology of ischemia-reperfusioninduced acute kidney injury (AKI). The p66shc adaptor protein is a newly recognized mediator of mitochondrial dysfunction, which might play a role in AKI-induced renal tubular injury. Oxidative stress-mediated Serine36 phosphorylation of p66shc facilitates its transportation to the mitochondria where it oxidizes cytochrome c and generates excessive amount of reactive oxygen species (ROS). The consequence is mitochondrial depolarization and injury. Earlier we determined that p66shc plays an essential role in injury of cultured mouse renal proximal tubule cells during oxidative stress. Here, we studied the role of p66shc in ROS generation and consequent mitochondrial dysfunction during oxidative injury in renal proximal tubule cells. We employed p66shc knockdown renal proximal tubule cells and cells that overexpress wild-type, Serine phosphorylation (S36A), or cytochrome c-binding (W134F) mutants of p66shc. Inhibition of the mitochondrial electron transport chain or the mitochondrial permeability transition revealed that hydrogen peroxide-induced injury is mitochondrial ROS and consequent mitochondrial depolarization dependent. We also found that through Ser36 phosphorylation and mitochondria/cytochrome c binding, p66shc mediates those effects. We propose a similar mechanism in vivo as we demonstrated mitochondrial binding of p66shc as well as its association with cytochrome c in the postischemic kidneys of mice. Thus, manipulating p66shc might offer a new therapeutic modality to ameliorate renal ischemic injury.en_US
dc.format.extentF1214 - F1221en_US
dc.publisherAMER PHYSIOLOGICAL SOCen_US
dc.titlep66SHC-mediated mitochondrial dysfunction in renal proximal tubule cells during oxidative injuryen_US
dc.typeJournal Article
rioxxterms.licenseref.startdate2010-05en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfAMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGYen_US
pubs.noteskeywords: reactive oxygen species;ACUTE KIDNEY INJURY; ISCHEMIA-REPERFUSION INJURY; EPIDERMAL-GROWTH-FACTOR; PERMEABILITY TRANSITION; LIFE-SPAN; ISCHEMIA/REPERFUSION INJURY; OXIDANT STRESS; CYCLOSPORINE-A; CYTOCHROME-C; DEATHen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Breast Cancer Research/Target Discovery & Apoptosis
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Target Discovery & Apoptosis
pubs.volume298en_US
pubs.embargo.termsNot knownen_US
icr.researchteamTarget Discovery & Apoptosisen_US
dc.contributor.icrauthorFaisal, Amiren_US


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