title: Expression and modulation of translocator protein and its partners by hypoxia reoxygenation or ischemia and reperfusion in porcine renal models.
abstract: 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-PK(1) 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-PK(1) 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 H(2)O(2)-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.
authors.affiliation: Inserm, U927, Faculté de Médecine, Université de Poitiers, 86021 Poitiers Cedex, France.
authors.forename: Frederic
authors.initials: F
authors.lastname: Favreau
authors.forename: Ludivine
authors.initials: L
authors.lastname: Rossard
authors.forename: Keqiang
authors.initials: K
authors.lastname: Zhang
authors.forename: Thibault
authors.initials: T
authors.lastname: Desurmont
authors.forename: Emilie
authors.initials: E
authors.lastname: Manguy
authors.forename: Aude
authors.initials: A
authors.lastname: Belliard
authors.forename: Stéphane
authors.initials: S
authors.lastname: Fabre
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Zeqiu
authors.initials: Z
authors.lastname: Han
authors.forename: Raphael
authors.initials: R
authors.lastname: Thuillier
authors.forename: Vassilios
authors.initials: V
authors.lastname: Papadopoulos
authors.forename: Thierry
authors.initials: T
authors.lastname: Hauet
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002470:Cell Survival / Q000502:physiology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology; D007674:Kidney Diseases / Q000378:metabolism* / Q000473:pathology; D007687:Kidney Tubules, Proximal / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress / Q000502:physiology; D010750:Phosphoproteins / Q000378:metabolism*; D011284:Pregnenolone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D013552:Swine; D000098682:Steroidogenic Acute Regulatory Protein
chemical_list: D002352:Carrier Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D000098682:Steroidogenic Acute Regulatory Protein; D011284:Pregnenolone; D002786:Cholesterol Side-Chain Cleavage Enzyme