Expression of peripheral benzodiazepine receptors and steroidogenic acute regulatory protein in post-ischemic kidney

ROLDÁN, LORENA; MOLINAS, SARA M.; PAGOTTO, MELINA; TRUMPER, LAURA; SERRA, ESTEBAN; MONASTEROLO, LILIANA

Rio de Janeiro. Brasil

Congreso; World Congress of Nephrology 2007; 2007

International Society of Nephrology

Expression of peripheral benzodiazepine receptors and steroidogenic acute regulatory protein in post-isquemic kidney Ma. Lorena Roldán, Sara Molinas1, Melina Pagotto1, Laura Trumper2, Esteban Serra1, Liliana Monasterolo1. Farmacología. Departamento de Ciencias Fisiológicas. Facultad Ciencias Bioquímicas y Farmacéuticas. Universidad Nacional de Rosario, Argentina. 1CONICET. 2CIUNR. World Congress of Nephrology 2007. Del 21 al 25 de abril de 2007. Rio de Janeiro. Brasil. Introduction Mitochondrial dysfunction has been identified as a possible early event in ischemia-reperfusion damage. The expression of peripheral benzodiazepine receptor (PBR), a structural mitochondrial protein, has been correlated to the level of preservation integrity in an autotransplanted pig kidney model (1). Recently, it was reported that selective ligands for PBR prevent renal injury induced by ischemia-reperfusion  (2). PBR are involved in several functions, including steroidogenesis. Steroidogenic acute regulatory protein (StAR) and PBR are indispensable elements of the steroidogenic machinery and function in a coordinated manner to transfer cholesterol into mitochondria (3). The objective of the present work was to evaluate the renal expression of PBR and StAR mRNA in an experimental model of ischemic acute renal failure. Materials and methods Male adults Wistar rats were used. Right renal artery was occluded with a vascular clamp for 40 minutes. After the ischemic period, the clamp was removed and blood reflow was allowed during 24 hours (IR). Sham operated animals were used as controls. Kidneys were excised and renal cortex was separated from medullary tissue. RNA was isolated using Trizol. mRNA levels of PBR and StAR were measured by reverse transcription- polymerase chain reaction (RT-PCR). GAPDH was co-amplified as control. PCR products were electrophoresed on a 1.2% agarose gel, stained with ethidium bromide and analyzed with GelPro program. Results The results showed a significant increase in the expression of  PBR mRNA (arbitrary units) (C: 0.46±0.05, IR: 0.77±0.05, p< 0.05), and a decrease in the expression of StAR mRNA (C: 0.28±0.06, IR: 0.15±0.02 , p< 0.05) in cortex tissue from IR kidneys. No changes in IR medullary tissue were detected. Conclusion These results indicated an augmented PBR and a diminished StAR mARN expression, suggesting that the steroidogenic machinery is affected during  renal injury induced by ischemia-reperfusion. Up-regulation of  PBR could compensate for the decrease in StAR. On this regard, it was reported that neurosteroids exhibit  cytoprotective effects in renal tubules subjected to hypoxia (4). Since rat kidney is capable of autonomous steroidogenesis (5), a possible contribution of nephrosteroids in the previously described (2) protective effects of PBR ligands against renal IR could be taken into account. 1) Transplantation 76:18, 2003, 2) J. Am. Soc. Nephrol. 15:2152, 2004 3) Mol. Endocrinol, doi:10.1210/me.2004-0307, 4) Am. J. Physiol. 273:F869, 1997 5) J. Steroid. Biochem. Mol. Biol. 91:49, 2004