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 (arsenite) increased the level of heat shock protein 27 (hsp27). The effect of arsenite was dose-dependent in the range of 50 to 200 microM. Arsenite also stimulated arachidonic acid release dose-dependently in the range between 50 and 200 microM in these cells. Both indomethacin, an inhibitor of cyclooxygenase, and nordihydroguaiaretic acid, a lipoxygenase inhibitor, significantly enhanced the arsenite-induced accumulation of hsp27. Melittin, an activator of phospholipase A2, significantly enhanced the arsenite-induced accumulation of hsp27. 12-O-Tetradecanoylphorbol-13-acetate (TPA), a protein kinase C (PKC)-activating phorbol ester, 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 nor the formation of choline and phosphocholine in these cells. These results suggest that the response to stress of hsp27 is coupled with the metabolic activity of the arachidonic acid cascade, and the activation of PKC inhibits the induction of hsp27 through the suppression of arachidonic acid release in osteoblast-like cells.
Suzuki
A
A
First Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kozawa
O
O
Oiso
Y
Y
Kato
K
K
D016475:3T3 Cells; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D018053:Arsenites / Q000494:pharmacology; D002794:Choline / Q000096:biosynthesis; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D007213:Indomethacin / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D009637:Masoprocol / Q000494:pharmacology; D008555:Melitten / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000096:biosynthesis; D011493:Protein Kinase C / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D018053:Arsenites; D006360:Heat-Shock Proteins; D007295:Inositol Phosphates; D010713:Phosphatidylcholines; D008555:Melitten; D016718:Arachidonic Acid; D009637:Masoprocol; D000242:Cyclic AMP; D011493:Protein Kinase C; C015001:arsenite; D002794:Choline; D013755:Tetradecanoylphorbol Acetate; D007213:Indomethacin