INVESTIGADORES
PODEROSO Juan Jose
congresos y reuniones científicas
Título:
Activation of mitochondrial ERK1/2 is required for PKA-dependent steroidogenesis in MA-10 cells.
Autor/es:
PODEROSO C; CONVERSO D; RODRÍGUEZ V; PAZ C; PODEROSO JJ; PODESTÁ EJ
Lugar:
Iguazú, Misiones
Reunión:
Congreso; XL Reunión de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular; 2004
Institución organizadora:
SAIB
Resumen:
Early steps of steroidogenesis occur in mitochondria and involve activation of Steroidogenic Acute Regulatory protein (StAR) leading to cholesterol import to the inner mitochondrial membrane, the rate-limiting step in steroid biosynthesis. Recently, our group and others reported that members of MAP kinases family, the extracellular signal-regulated kinases 1/2 (ERK1/2), are activated by phosphorylation in mitochondria. To investigate a putative nongenomic ERK mitochondrial effect on steroidogenesis, MA-10 cells were arrested in G1 phase and stimulated with 8Br-cAMP (0.5mM) in the presence or absence of two inhibitors of MEK1/2 (MAP kinase kinase, upstream ERK kinase), PD98056 and U0126. Both compounds inhibited 8Br-cAMP stimulated-steroid production without affecting hormonal basal level or PKA activity. MEK1/2 and ERK1/2 resulted phosphorylated with maximal activity after 5 min of stimulation that decreased up to 1 h, without modifying total kinase expression. A similar time-course activation of constitutive ERK1/2 was found in purified non-contaminated mitochondria as assessed by Western blot or by co-localization in immunocytochemistry with mitotracker red, a mitochondrial dye. This pattern of cAMP activation was inhibited by H-89, a permeable PKA inhibitor. It is surmised that sustained mitochondrial ERK activity via PKA is required to StAR-dependent cholesterol transport and steroidogenesis in cAMP-stimulated MA-10 cells.