RESTORATION OF THE GLUCOCORTICOID RECEPTOR FUNCTION BY THE PHOSPHODIESTER COMPOUND OF VITAMIN-C AND VITAMIN-E, EPC-K1 (L-ASCORBIC-ACID -2-(4,8,12-TRIMETHYLTRIDECYL)-2H-1-BENZOPYRAN-6-YL HYDROGEN PHOSPHATE] POTASSIUM-SALT), VIA A REDOX-DEPENDENT MECHANISM

Citation
K. Okamoto et al., RESTORATION OF THE GLUCOCORTICOID RECEPTOR FUNCTION BY THE PHOSPHODIESTER COMPOUND OF VITAMIN-C AND VITAMIN-E, EPC-K1 (L-ASCORBIC-ACID -2-(4,8,12-TRIMETHYLTRIDECYL)-2H-1-BENZOPYRAN-6-YL HYDROGEN PHOSPHATE] POTASSIUM-SALT), VIA A REDOX-DEPENDENT MECHANISM, Biochemical pharmacology, 56(1), 1998, pp. 79-86
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Pharmacy",Biology
Journal title
ISSN journal
0006-2952
Volume
56
Issue
1
Year of publication
1998
Pages
79 - 86
Database
ISI
SICI code
0006-2952(1998)56:1<79:ROTGRF>2.0.ZU;2-#
Abstract
We examined the effect of the novel antioxidant EPC-K1 (L-ascorbic aci d 2-[3,4-dihydro-2,5,7,8-tetramethyl-2-(4,8,1 2-trimethyltridecyl)-2H- 1-benzopyran-6-yl hydrogen phosphate] potassium salt) on glu cocortico id receptor function. We used cloned CHOpMTGR cells in which human glu cocorticoid receptor cDNA was stably transfected and the glucocorticoi d receptor was expressed at high levels. We recently suggested that gl ucocorticoid-mediated gene expression is modulated via the cellular re dox state [Makino et at., J Clin Invest 98: 2469-2477, 1996]. In the p resent study, this issue was clearly evidenced by the finding that cel lular treatment with H2O2 decreased the ligand binding and transcripti onal activity of the glucocorticoid receptor, and we showed that these inhibitory effects of H2O2 were effectively titrated by the addition of EPC-K1. Moreover, DNA-binding activity of the bacterially expressed DNA-binding domain of the glucocorticoid receptor was repressed by th e thiol-oxidizing reagent diamide; EPC-K1 also counteracted this repre ssive effect of diamide. Thus, the redox state was indicated to influe nce glucocorticoid receptor function at various steps, and EPC-K1 may be useful in restoring the cellular glucocorticoid-responsiveness in o xidative conditions. BIOCHEM PHARMACOL 56;1:79-86, 1998. (C) 1998 Else vier Science Inc.