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This Article Full Text Full Text (PDF) All Versions of this Article: 297/1/F177    most recent 90422.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Favreau, F. Articles by Hauet, T. PubMed PubMed Citation Articles by Favreau, F. Articles by Hauet, T.

Expression and modulation of translocator protein and its partners by hypoxia reoxygenation or ischemia and reperfusion in porcine renal models

¹Inserm, U927, Faculté de Médecine, Université de Poitiers, Poitiers; ²Division of Molecular Medicine, Beckman Research Institute of the City of Hope, Duarte, California; ³INRA, Physiologie de la Reproduction et des Comportements, INRA-CNRS-Université de Tours-Haras Nationaux, Nouzilly; ⁴Research Institute, McGill University Health Centre and Department of Medicine, McGill University, Montreal, Quebec, Canada; and ⁵INRA, Génétique Expérimentale en Production Animale, Département de Génétique, Domaine Expérimental du Magneraud, Surgères, France

Submitted 18 July 2008 ; accepted in final form 17 April 2009

Translocator protein (TSPO), formerly known as the peripheral-type benzodiazepine receptor, is an 18-kDa drug- and cholesterol-binding protein localized to the outer mitochondrial membrane and implicated in a variety of cell and mitochondrial functions. To determine the role of TSPO in ischemia-reperfusion injury (IRI), we used both in vivo and in vitro porcine models: an in vivo renal ischemia model where different conservation modalities were tested and an in vitro model where TSPO-transfected porcine proximal tubule LLC-PK₁ cells were exposed to hypoxia and oxidative stress. The expression of TSPO and its partners in steroidogenic cells, steroidogenic acute regulatory protein (StAR) and cytochrome P-450 side chain cleavage CYP11A1, as well as the impact of TSPO overexpression and exposure to TSPO ligands in vitro in hypoxia-ischemia conditions were investigated. Hypoxia induced caspase activation, reduction of ATP content, and LLC-PK₁ cell death. Transfection and overexpression of TSPO rescued the cells from the detrimental effects of hypoxia and reoxygenation. Moreover, TSPO overexpression was accompanied by a reduction of H₂O₂-induced necrosis. TSPO drug ligands did not affect TSPO-mediated functions. In vivo, TSPO expression was modulated by IRI and during regeneration particularly in proximal tubule cells, which do not express this protein at the basal level. Under the same conditions, StAR and CYP11A1 protein and gene expression was reduced without apparent relation to TSPO changes. Pregnenolone was identified and measured in the pig kidney. Pregnenolone synthesis was not affected by the experimental conditions used. Taken together, these results indicate that changes in TSPO expression in kidney regenerating tissue could be important for renal protection and maintenance of kidney function.

ischemia-reperfusion injury; translocator protein; renal regeneration