Alpha2 adrenoreceptor agonist regulates protein kinase C-induced heat shock protein 27 phosphorylation in C6 glioma cells.
Dexmedetomidine (Dexmd), a potent and highly specific alpha(2) adrenoreceptor agonist, is an efficient therapeutic agent for sedation. Dexmd has been recently reported to have a neuroprotective effect. Heat shock protein (HSP) 27, a low-molecular weight HSP has been shown to be expressed following cerebral ischemia in astrocytes but not in neurons. HSP27 expression is involved in ischemic tolerance of the brain. This study investigated the effect of Dexmd on HSP27 in rat C6 glioma cells. 12-O-tetradecanoylphorbol-13-actate (TPA), a direct activator of protein kinase C (PKC), stimulated the phosphorylation of HSP27 at Ser82, but not Ser15 in a time-dependent manner. Prostaglandin (PG) E(1) or PGE(2) which activates the adenylyl cyclase-cAMP system as well as forskolin and dibutyryl-cAMP, suppressed the TPA-induced phosphorylation of HSP27. Dexmd reversed the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system. Therefore, these results strongly suggest that Dexmd reverses the suppression of HSP27 phosphorylation by the adenylyl cyclase-cAMP system activation through the inhibition of its system in C6 cells. alpha(2) Adrenoreceptor agonists may therefore show a neuroprotective effect through the modification of HSP27 phosphorylation induced by PKC activation.
Tanabe
Kumiko
K
Department of Anesthesiology and Pain Medicine, Gifu University Graduate School of Medicine, Gifu, Japan. kumiko-t@m2.gyao.ne.jp
Takai
Shinji
S
Matsushima-Nishiwaki
Rie
R
Kato
Kanefusa
K
Dohi
Shuji
S
Kozawa
Osamu
O
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000527:Alprostadil / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D045744:Cell Line, Tumor; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D020927:Dexmedetomidine / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology; D004347:Drug Interactions; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D005910:Glioma; D006360:Heat-Shock Proteins / Q000378:metabolism*; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000494:pharmacology*; D051381:Rats; D012694:Serine / Q000378:metabolism; D013997:Time Factors
D000316:Adrenergic alpha-Agonists; D006360:Heat-Shock Proteins; D010703:Phorbol Esters; D005576:Colforsin; D012694:Serine; D003994:Bucladesine; D020927:Dexmedetomidine; C032974:12-O-retinoylphorbol-13-acetate; D000242:Cyclic AMP; D011493:Protein Kinase C; D000527:Alprostadil; D015232:Dinoprostone