Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury.

TitleMitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury.
Publication TypeJournal Article
Year of Publication2011
AuthorsSzeto HH, Liu S, Soong Y, Wu D, Darrah SF, Cheng F-Y, Zhao Z, Ganger M, Tow CY, Seshan SV
JournalJ Am Soc Nephrol
Volume22
Issue6
Pagination1041-52
Date Published2011 Jun
ISSN1533-3450
KeywordsAcute Kidney Injury, Adenosine Triphosphate, Animals, Antioxidants, Apoptosis, Kidney Tubules, Male, Mitochondria, Mitochondrial Membrane Transport Proteins, Mitochondrial Permeability Transition Pore, Models, Animal, Oligopeptides, Oxidative Stress, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Regeneration, Reperfusion Injury
Abstract

The burst of reactive oxygen species (ROS) during reperfusion of ischemic tissues can trigger the opening of the mitochondrial permeability transition (MPT) pore, resulting in mitochondrial depolarization, decreased ATP synthesis, and increased ROS production. Rapid recovery of ATP upon reperfusion is essential for survival of tubular cells, and inhibition of oxidative damage can limit inflammation. SS-31 is a mitochondria-targeted tetrapeptide that can scavenge mitochondrial ROS and inhibit MPT, suggesting that it may protect against ischemic renal injury. Here, in a rat model of ischemia-reperfusion (IR) injury, treatment with SS-31 protected mitochondrial structure and respiration during early reperfusion, accelerated recovery of ATP, reduced apoptosis and necrosis of tubular cells, and abrogated tubular dysfunction. In addition, SS-31 reduced medullary vascular congestion, decreased IR-mediated oxidative stress and the inflammatory response, and accelerated the proliferation of surviving tubular cells as early as 1 day after reperfusion. In summary, these results support MPT as an upstream target for pharmacologic intervention in IR injury and support early protection of mitochondrial function as a therapeutic maneuver to prevent tubular apoptosis and necrosis, reduce oxidative stress, and reduce inflammation. SS-31 holds promise for the prevention and treatment of acute kidney injury.

DOI10.1681/ASN.2010080808
Alternate JournalJ Am Soc Nephrol
PubMed ID21546574
PubMed Central IDPMC3103724
Related Faculty: 
Surya V. Seshan, M.D.

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