Effects of Intracellular Glutahione Levels on Human Insulin Gene Expression.

Accession number;01A0391388
Title;Effects of Intracellular Glutahione Levels on Human Insulin Gene Expression.
Author; OZAKI MASAKO (Nagasakidai I Daiichinaika) YAMASAKI HIRONORI (Nagasakidai I Daiichinaika) YAMAGUCHI YOSHIHIKO (Nagasakidai I Daiichinaika) KONDO HIDEAKI (Nagasakidai I Daiichinaika) FUJITA NARUHIRO (Nagasakidai I Daiichinaika) ABE TAKAHIRO (Nagasakidai I Daiichinaika) EGUCHI KATSUMI (Nagasakidai I Daiichinaika) KIJIMA HIROSHI (Tokaidai I Byotaishindankeibyorigaku) KONDO TAKAHITO (Nagasaki Univ.,Atomic Bomb Desease Inst.,Div. of Sci. Data Registry)
Journal Title;Journal of the Japan Diabetic Society
Journal Code:Z0279B
ISSN:0021-437X
VOL.44;NO.2;PAGE.127-133(2001)
Figure&Table&Reference;FIG.4, REF.19
Pub. Country;Japan
Language;Japanese
Abstract;Glutathione (GSH) is involved in deoxidation and elimination of hydrogen peroxide and other reactive oxygen species, and plays an important role in the antioxidant system. To investigate the effect of GSH on insulin gene expression, we established insulin secreting cells MIN 6 that stably transfected with the ribozyme against .GAMMA.-glutamylcysteine synthetase (.GAMMA.-GCS) an enzyme limiting GSH synthesis. Resultant cell lines exhibited suppressed intracellular GSH synthesis. We transiently transfected luciferase expression vector driven by preproinsulin gene promoter region-1998 to +237 to ribozyme transfected MIN 6 cells. Luciferase activity increased about 15 and 5 times in ribozyme transfected MIN 6 cells compared to untransfected MlN 6 cells and MOCK. Transfection with deletion constructs (-879 to +273) was shown 30% attenuation of insulin promoter activity in ribozyme transfected MIN 6 cells compared to that seen with the full promoter length, while activity was preserved in untransfected MIN 6 cells and MOCK. These results suggest that lowering of intracellular GSH may in part regulate insulin gene expression in insulin secreting cells. (author abst.)