tailieunhanh - Báo cáo khoa học: cAMP increases mitochondrial cholesterol transport through the induction of arachidonic acid release inside this organelle in Leydig cells

We have investigated the direct effect of arachidonic acid on cholesterol transport in intact cells or isolated mitochondria from steroidogenic cells and the effect of cyclic-AMP on the specific release of this fatty acid inside the mitochondria. We show for the first time that cyclic-AMP can regulate the release of arachidonic acid in a specialized compartment of MA-10 Leydig cells, . | ỊFEBS Journal cAMP increases mitochondrial cholesterol transport through the induction of arachidonic acid release inside this organelle in Leydig cells Ana Fernanda Castillo Fabiana Cornejo Maciel Rocio Castilla Alejandra Duarte Paula Maloberti Cristina Paz and Ernesto J. Podesta Department of Biochemistry Schoolof Medicine University of Buenos Aires Argentina Keywords acyl-CoA synthetase acyl-CoA thioesterase arachidonic acid compartmentalization Leydig cells steroidogenesis Correspondence E. J. Podesta Department of Biochemistry Schoolof Medicine University of Buenos Aires Paraguay 2155-5th C1121ABG Buenos Aires Argentina Fax 54 11 45083672 ext. 31 Tel 54 11 45083672 ext. 36 E-mail biohrdc@ Received 27 July 2006 revised 23 August 2006 accepted 12 September 2006 doi We have investigated the direct effect of arachidonic acid on cholesterol transport in intact cells or isolated mitochondria from steroidogenic cells and the effect of cyclic-AMP on the specific release of this fatty acid inside the mitochondria. We show for the first time that cyclic-AMP can regulate the release of arachidonic acid in a specialized compartment of MA-10 Leydig cells . the mitochondria and that the fatty acid induces cholesterol transport through a mechanism different from the classical pathway. Arachidonic acid and arachidonoyl-CoA can stimulate cholesterol transport in isolated mitochondria from nonstimulated cells. The effect of arach-idonoyl-CoA is inhibited by the reduction in the expression or in the activity of a mitochondrial thioesterase that uses arachidonoyl-CoA as a substrate to release arachidonic acid. cAMP-induced arachidonic acid accumulation into the mitochondria is also reduced when the mitochondrial thioesterase activity or expression is blocked. This new feature in the regulation of cholesterol transport by arachidonic acid and the release of arachidonic acid in specialized compartment of the cells could offer novel .