کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514626 1118475 2008 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Expression of cytochrome P450 2A5 in a glucose-6-phosphate dehydrogenase-deficient mouse model of oxidative stress
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Expression of cytochrome P450 2A5 in a glucose-6-phosphate dehydrogenase-deficient mouse model of oxidative stress
چکیده انگلیسی

Murine hepatic cytochrome P450 2A5 (CYP2A5), unlike most CYP enzymes, is upregulated during hepatitis and hepatotoxic conditions, but the common stimulus for its induction remains unknown. We investigated the involvement of oxidative stress in the regulation of CYP2A5 expression using an oxidative stress-sensitive glucose-6-phosphate dehydrogenase (G6PD)-deficient mouse model. Treatment of deficient and wild-type mice with the prototypical CYP2A5-inducer pyrazole for 72 h led to a significantly greater degree of induction of CYP2A5 mRNA, protein and activity in deficient mice, with the greatest increase observed in animals homozygous for the deficiency. However, markers of oxidative stress including protein carbonyl, 8-hydroxydeoxyguanosine, malondiadehyde and 4-hydroxyalkenal levels were unaltered with pyrazole treatment. Furthermore, CYP2A5 expression was not altered in G6PD-deficient mice treated with the pro-oxidant menadione whereas DNA, lipid, and protein markers of oxidative stress were significantly increased. The antioxidant polyethylene glycol-conjugated catalase, while decreasing oxidative stress in menadione-treated mice, did not prevent the induction of CYP2A5 by pyrazole. Finally, the ER stress marker protein, GRP78, was increased following pyrazole treatment in G6PD-deficient compared to wild-type mice. These findings do not support a central role for generalized cellular oxidative stress in the regulation of CYP2A5 and suggest that additional factors related to G6PD-deficiency, such as ER stress, may be involved.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 75, Issue 5, 1 March 2008, Pages 1230–1239
نویسندگان
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