INBIOMED   24026
INSTITUTO DE INVESTIGACIONES BIOMEDICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Relationship between SHP2, Acsl4 and steroidogenesis
Autor/es:
COOKE M; MALOBERTI P; PODESTÁ EJ; CORNEJO MACIEL F
Lugar:
Foz de Iguazu, Parana
Reunión:
Congreso; XL Annual Meeting of the Brazilian Society for Biochemestry and Molecular Biology (SBBq); 2012
Institución organizadora:
SBBq
Resumen:
Steroid biosynthesis is dependent on PKA-mediated events triggered by trophic hormones. Some of such events are the dephosphorylation of proteins on tyrosine residues -mediated by hormone-activated protein tyrosine phosphatases (PTPs)-, the release of arachidonic acid (AA) -in which the acyl-CoA synthetase Acsl4 is involved- and the induction of StAR protein -key regulator of steroidogenesis acting on cholesterol transport across the mitochondrial membrane-. Acsl4 is implicated in fatty acid metabolism with marked preference for AA. Since Acsl4 protein expression requires PTP activity, in this study we aimed to identify the PTP involved in Acsl4 expression and steroidogenesis. For that purpose, we used a plasmid-mediated gene transfer and RNAi-mediated gene silencing approach to modify intracellular levels of SHP2 in MA-10 Leydig cells and determined Acsl4 and StAR mRNA (RT-PCR) and protein levels (Western blot) and steroid production (radioimmunoassay). Overexpression of an active form of SHP2 increased the effect of cAMP on StAR and Acsl4 protein levels in MA-10 steroidogenic cells. The effects could be specifically attributed to SHP2 since knock-down of the phosphatase impeded cAMP action on Acsl4 and StAR mRNA and protein levels. Through the action on Acsl4 and StAR protein levels, SHP2 affected the steroidogenic capacity of MA-10 cells: overexpression or knock-down of SHP2 led to increased or decreased steroid production respectively. In summary, we describe for the first time the involvement of SHP2 activity in the regulation of the expression of the fatty acid-metabolizing enzyme Acsl4 and finally in the regulation of steroidogenesis.