| Involvement of peripheral benzodiazepine receptor in the oxidative stress, death-signaling pathways, and renal injury induced by ischemia-reperfusion. | |
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MedLine Citation:
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PMID: 15284300 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The peripheral benzodiazepine receptor (PBR) is a critical component of the mitochondrial permeability transition pore, which is involved in the regulation of cell death. In the present study we investigated the role of PBR in the regulation of signaling pathways leading to apoptotic and necrotic damage and renal dysfunction in a rat model of ischemia-reperfusion. Renal ischemia-reperfusion led to extended tubular apoptosis and necrosis that were associated with peroxidative damage, high levels of proapoptotic Bax expression, and low levels of antiapoptotic Bcl-2 expression, cleavage of death substrate, poly(ADP-ribose) polymerase (PARP), and activation of a key effector of apoptosis, caspase-3. Rat pretreatment with a novel PBR antagonist, SSR180575, significantly decreased postreperfusion oxidative stress and tubular apoptosis and necrosis. This effect was associated with inhibition of caspase-3 activation and PARP cleavage, upregulation of Bcl-2, and downregulation of Bax. Furthermore, inhibition of PBR accelerated the recovery of normal renal function, as assessed by measurement of levels of plasma creatinine and blood urea nitrogen. These findings reveal a role for PBR as a modulator of necrotic and apoptotic cell death induced by ischemia-reperfusion and suggest that regulation of PBR may provide new therapeutic implications for the prevention of acute renal failure. |
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Authors:
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Oxana R Kunduzova; Ghislaine Escourrou; France De La Farge; Robert Salvayre; Marie-Hélène Séguélas; Nathalie Leducq; Françoise Bono; Jean-Marc Herbert; Angelo Parini |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Journal of the American Society of Nephrology : JASN Volume: 15 ISSN: 1046-6673 ISO Abbreviation: J. Am. Soc. Nephrol. Publication Date: 2004 Aug |
Date Detail:
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Created Date: 2004-08-02 Completed Date: 2004-09-20 Revised Date: 2006-11-15 |
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: 2152-60 Citation Subset: IM |
Affiliation:
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INSERM U388, Institut Louis Bugnard, CHU Rangueil, Bat. L3, 31403 Toulouse Cedex 4, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Acetamides
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pharmacology Animals Apoptosis / physiology Hydrogen Peroxide / pharmacology Indoles / pharmacology Kidney Failure, Acute / metabolism*, pathology* Male Necrosis Oxidants / pharmacology Oxidative Stress / drug effects, physiology Rats Receptors, GABA-A / metabolism* Reperfusion Injury / metabolism*, pathology* Signal Transduction / physiology |
| Chemical | |
Reg. No./Substance:
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0/Acetamides; 0/Indoles; 0/Oxidants; 0/Receptors, GABA-A; 0/SSR180575; 7722-84-1/Hydrogen Peroxide |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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