MOLECULAR EVENTS TRIGGERED BY HEAT SHOCK IN STEROIDOGENIC CELLS.

A. GOROSTIZAGA, P. MALOBERTI, L. BRION, V. SALGADO, C. PODEROSO, F. CORNEJO MACIEL, E.J. PODESTÁ, CRISTINA PAZ.

New Orleans, USA

Conferencia; XIth Adrenal Cortex Conference; 2004

Bernard Schimmer and Alexander Brownie, members of the Organizing Committee

MOLECULAR EVENTS TRIGGERED BY HEAT SHOCK IN STEROIDOGENIC CELLS A. Gorostizaga, P. Maloberti, L. Brion, V. Salgado, C. Poderoso, F. Cornejo Maciel, E.J. Podestá and Cristina Paz Dpt. Biochemistry, School of Medicine, University of Buenos Aires, Argentina MAPK phosphatase-1 (MKP-1), a phosphatase specifically involved in the inactivation of MAPK family members, is induced by mitogenic stimuli and stress conditions. Here we describe the effect of heat shock (HS, 10 min, 45 °C ) on MKP-1 mRNA and protein levels and on MAPKs activities in steroidogenic cells. In MA-10 cells, Northern and Western blot analysis showed a transient increase on MKP-1 messenger and protein levels. The effect on the messenger was significant 15 min after treatment, maximal at 60 min (3 fold) and declined thereafter. Western blot analysis performed with antibodies against the phosphorylated forms of ERK1/2 and JNK revealed that HS also produced the transient activation of these kinases. Comparison of the temporal profiles of MKP-1 protein induction and MAPKs phospho-dephosphorylation suggests that MKP-1 induction could contribute to ERK1/2 and JNK inactivation after HS. Furthermore, HS produced a strong HSP72 induction. In Y1 cells, HS also modified MAPKs phosphorylation state, and produced a less evident induction of HSP72. In addition to the already described MKP-1 induction by ACTH/cAMP and its role in steroidogenesis, here we demonstrate the induction of this enzyme by a stress condition. In this case, MKP-1 could be involved in the adaptation of the cells to the injury through the modulation of MAPKs activities.