| Mitochondria-targeted peptide accelerates ATP recovery and reduces ischemic kidney injury. | |
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MedLine Citation:
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PMID: 21546574 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Hazel H Szeto; Shaoyi Liu; Yi Soong; Dunli Wu; Shaun F Darrah; Feng-Ying Cheng; Zhihong Zhao; Michael Ganger; Clara Y Tow; Surya V Seshan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2011-05-05 |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 22 ISSN: 1533-3450 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2011 Jun |
Date Detail:
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Created Date: 2011-06-01 Completed Date: 2011-08-25 Revised Date: 2012-06-19 |
Medline Journal Info:
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Nlm Unique ID: 9013836 Medline TA: J Am Soc Nephrol Country: United States |
Other Details:
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Languages: eng Pagination: 1041-52 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, Weill Cornell Medical College, New York, NY 10021, USA. hhszeto@med.cornell.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acute Kidney Injury
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etiology*,
physiopathology,
prevention & control* Adenosine Triphosphate / metabolism* Animals Antioxidants / pharmacology, therapeutic use* Apoptosis / drug effects, physiology Kidney Tubules / drug effects, physiology Male Mitochondria / drug effects, physiology Mitochondrial Membrane Transport Proteins / drug effects, physiology Models, Animal Oligopeptides / pharmacology, therapeutic use* Oxidative Stress / drug effects, physiology Rats Rats, Sprague-Dawley Reactive Oxygen Species / metabolism Regeneration / drug effects, physiology Reperfusion Injury / complications* |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Mitochondrial Membrane Transport Proteins; 0/Oligopeptides; 0/Reactive Oxygen Species; 0/arginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamide; 0/mitochondrial permeability transition pore; 56-65-5/Adenosine Triphosphate |
| Comments/Corrections | |
Comment In:
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J Am Soc Nephrol. 2011 Jun;22(6):986-9
[PMID:
21566050
]
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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