Enhancement of stress-induced synthesis of hsp27 and alpha B crystallin by modulators of the arachidonic acid cascade.
The regulation by intrinsic factors of responses to stress of two small stress proteins, hsp27 and alpha B crystallin, was examined in C6 rat glioma cells. Levels of hsp27 and alpha B crystallin were low in C6 glioma cells in confluent cultures. However, levels of the two proteins increased after exposure of cells to heat (42 degrees C for 30 min) or arsenite (50 microM for 1 h) stress. When cells were exposed to arsenite or hear in the presence of indomethacin (50 microM), an inhibitor of cyclooxygenase, or in the presence of nordihydroguaiaretic acid (NDGA; 50 microM), an inhibitor of lipoxygenase, induction of hsp27 and alpha B crystallin was markedly stimulated as detected by specific immunoassays, Western blot analysis, and Northern blot analysis. The presence of melittin (1 microM), an activator of phospholipase A2, during the stress period also stimulated the induction of the two proteins. The expression of hsp70 to each stress was also enhanced in the presence of indomethacin, NDGA, or melittin. The gel mobility shift assay revealed that these chemicals prolonged the arsenite-induced activation of heat shock element (HSE)-binding activity of heat shock transcriptional factor (HSF) in cells. Induction of hsp27 and alpha B crystallin in adrenal glands of heat-stressed (42 degrees C for 15 min) rats was also enhanced by prior injection of aspirin, another inhibitor of cyclooxygenase. These results indicate that the responses to stress of hsp27 and alpha B crystallin, as well as the response of hsp70, are coupled with the metabolic activity of the arachidonic acid cascade and the mechanism for regulation of stress responses observed in C6 cells is operative in tissues and organs in vivo.
Ito
H
H
Department of Biochemistry, Aichi Human Service Center, Japan.
Hasegawa
K
K
Inaguma
Y
Y
Kozawa
O
O
Kato
K
K
D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D018053:Arsenites / Q000494:pharmacology; D001483:Base Sequence; D003459:Crystallins / Q000096:biosynthesis*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004789:Enzyme Activation; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D007213:Indomethacin / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008297:Male; D009637:Masoprocol / Q000494:pharmacology*; D008555:Melitten / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D018053:Arsenites; D003459:Crystallins; D016861:Cyclooxygenase Inhibitors; D006360:Heat-Shock Proteins; D016859:Lipoxygenase Inhibitors; D008555:Melitten; D016718:Arachidonic Acid; D009637:Masoprocol; D010741:Phospholipases A; D054467:Phospholipases A2; C015001:arsenite; D007213:Indomethacin