HORMONAL REGULATION OF ARACHIDONIC ACID RELEASE IN A SPECIFIC COMPARTMENT OF THE CELL

CASTILLO, FERNANDA; CORNEJO MACIEL, FABIANA; CASTILLA, ROCÍO; MALOBERTI, PAULA; PAZ, CRISTINA; PODESTÁ, ERNESTO J.

Rosario, Santa Fe, Argentina

Congreso; XLII Annual Meeting of Argentine Society for Biochemistry and Molecular Biology (SAIB); 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The mechanism involved in the compartamentalization of longchain acyl-CoA esters and free fatty acids are important unresolved issues. The simple structure of arachidonic acid (AA) and the natural occurrence of so many close chemical analogues are associated with a lack of specificity. The selective actions of free AA may be explained simply by its specific release under physiological conditions and by the absence of such mechanism for releasing other long-chain fatty acids. Recently, using steroidogenic cells as experimental system, we have described an alternative releasing mechanism of AA with the participation of an acyl-CoA synthetase (ACS4) and a mitochondrial acyl-CoA thioesterase (Acot2). Moreover, we have described a direct effect of AA on cholesterol transport into the mitochondria. Therefore, the purpose of this work was to study the hormonal regulation of AA release into the mitochondria. MA-10 Leydig cells were labeled with [1-14 C] AA and then incubated in the presence or absence of 8Br-cAMP (1mM) for 30 minutes. 8Br-cAMP increased the accumulation of AA into the mitochondria 3 times compared with no stimulated conditions. Inhibition of the activity or expression of Acot2 significantly reduces AA accumulation into the mitochondria. In conclusion, we show for the first time that cAMP can release AA in special compartment of the cell, e.g. the mitochondria.