Contrasting effects of midazolam on induction of heat shock protein 27 by vasopressin and heat in aortic smooth muscle cells.
We previously showed that vasopressin stimulates the induction of heat shock protein (HSP) 27, a low molecular-weight HSP, through protein kinase C activation in aortic smooth muscle A10 cells. In the present study, we examined the effects of midazolam, an intravenous anesthetic, on the HSP27 induction stimulated by vasopressin, heat, or sodium arsenite (arsenite) in A10 cells. Midazolam inhibited the accumulation of HSP27 induced by vasopressin or 12-O-tetradecanoylphorbol 13-acetate (TPA), a direct activator of protein kinase C. Midazolam also reduced the vasopressin-induced level of the mRNA for HSP27. In contrast, midazolam enhanced the HSP27-accumulation induced by heat or arsenite. Midazolam also enhanced the heat-increased level of the mRNA for HSP27. However, midazolam had no effect on the dissociation of the aggregated form of HSP27 following stimulation by vasopressin, heat, or arsenite. These results suggest that midazolam suppresses vasopressin-stimulated HSP27 induction in vascular smooth muscle cells, and that this inhibitory effect is exerted at a point downstream from protein kinase C. In contrast, midazolam enhanced heat- or arsenite-stimulated HSP27 induction. Thus, midazolam has dual effects on the HSP27 induction stimulated by various stresses in vascular smooth muscle cells.
Tanabe
K
K
Department of Pharmacology, Gifu University School of Medicine, Gifu, Japan.
Kozawa
O
O
Niwa
M
M
Yamomoto
T
T
Matsuno
H
H
Ito
H
H
Kato
K
K
Dohi
S
S
Uematsu
T
T
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000166:cytology; D018053:Arsenites / Q000494:pharmacology; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000096:biosynthesis* / Q000235:genetics; D006358:Hot Temperature; D008874:Midazolam / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology*
D018686:Anesthetics, Intravenous; D018053:Arsenites; D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D014667:Vasopressins; C015001:arsenite; D013755:Tetradecanoylphorbol Acetate; D008874:Midazolam