کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1992071 1541065 2008 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Modification of microsomal 11β-HSD1 activity by cytosolic compounds: Glutathione and hexose phosphoesters
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Modification of microsomal 11β-HSD1 activity by cytosolic compounds: Glutathione and hexose phosphoesters
چکیده انگلیسی

11β-Hydroxysteroid dehydrogenase1(11β-HSD1) can serve either as an oxo-reductase or dehydrogenase determined by the redox state in the endoplasmic reticulum (ER). This bidirectional enzyme governs paracrine glucocorticoid production. Recent in vitro studies have underscored the key role of cytoplasmic glucose-6-phosphate (G6P) in controlling the flux direction of 11βHSD-1 by altering the intraluminal ER NADPH/NADP ratio. The hypothesis that other hexose phosphoesters or the plentiful cellular oxidative protector glutathione could also regulate microsomal 11βHSD-1 activity was tested. Fructose-6-phosphate increased the activity of 11β-HSD1 reductase in isolated rat and porcine liver microsomes but not porcine fat microsomes. Moreover, oxidized glutathione (GSSG) attenuated 11β-HSD1 reductase activity by 40% while reduced glutathione (GSH) activated the reductase in liver. Fat microsomes were unaffected because they lack glutathione reductase. Nonetheless, another oxidizing agent, hydrogen peroxide (0.5 mM), inhibited both fat and liver 11β-HSD1 reductase. Consistent with the major role of the redox state, 2.5 mM GSSG and hydrogen peroxide augmented the 11β-HSD1 dehydrogenase, antithetical to the reductase, by 20–30% in liver microsomes. Given the key role of reactive oxygen species and hexose phosphate accumulation in the pathoetiology of obesity and diabetes, these compounds might also modify 11β-HSD1 in these conditions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Steroid Biochemistry and Molecular Biology - Volume 111, Issues 1–2, July 2008, Pages 18–23
نویسندگان
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