PROTEIN-KINASE-C ACTIVATION INHIBITS STRESS-INDUCED SYNTHESIS OF HEAT-SHOCK-PROTEIN-27 IN OSTEOBLAST-LIKE CELLS - FUNCTION OF ARACHIDONIC-ACID

Exposure of osteoblast-like MC3T3-E1 cells to sodium arsenite (arsenit e) increased the level of heat shock protein 27 (hsp27). The effect of arsenite was dose-dependent in the range of 50 to 200 mu M. Arsenite also stimulated arachidonic acid release dose-dependently in the range between 50 and 200 mu M in these cells. Both indomethacin, an inhibit or of cyclooxygenase, and nordihydroguaiaretic acid, a lipoxygenase in hibitor, significantly enhanced the arsenite-induced accumulation of h sp27. Melittin, an activator of phospholipase A(2), Significantly enha nced the arsenite-induced accumulation of hsp27. 12-O-Tetradecanoylpho rbol-13-acetate (TPA), a protein kinase C (PKC)-activating phorbol est er, inhibited the arsenite-induced accumulation of hsp27. In contrast, 4 alpha-phorbol 12,13-didecanoate (4 alpha-PDD), a PKC-nonactivating phorbol ester, had little effect. TPA suppressed the arsenite-induced arachidonic acid release, but 4 alpha-PDD had little effect. Arsenite no longer affected cAMP accumulation, inositol phosphates formation no r the formation of choline and phosphocholine in these cells. These re sults suggest that the response to stress of hsp27 is coupled with the metabolic activity of the arachidonic acid cascade, and the activatio n of PKC inhibits the induction of hsp27 through the suppression of ar achidonic acid release in osteoblast-like cells. (C) 1996 Wiley-Liss, Inc.