کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2601409 1133318 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Ethanol-induced expression of glutamate–cysteine ligase catalytic subunit gene is mediated by NF-κB
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Ethanol-induced expression of glutamate–cysteine ligase catalytic subunit gene is mediated by NF-κB
چکیده انگلیسی

Glutamate–cysteine ligase is a rate-limiting enzyme in the de novo synthesis of glutathione, a known scavenger of electrophiles and reactive oxygen species. Glutamate–cysteine ligase catalytic subunit (GCLC) is regulated transcriptionally by nuclear factor erythroid 2-related factor 2 (Nrf2). It has been reported that ethanol induces human GCLC production via Nrf2-mediated transactivation of the antioxidant-responsive element (ARE). Here, the luciferase reporter assay revealed the presence of an ethanol-responsive element in the human GCLC promoter; it spanned bases −1432 to −832 in hepatocytes and HepG2 cells transfected with cytochrome P450 2E1 (CYP2E1). The region lacked an ARE but had a putative nuclear factor-κB (NF-κB) element. NF-κB DNA-binding activity was activated in response to ethanol treatment. CYP2E1 expression was required for GCLC promoter-driven gene expression and the activation of NF-κB. Thus ethanol-induced GCLC transcription is mediated by not only Nrf2 but also NF-κB.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 185, Issue 2, 10 March 2009, Pages 110–115
نویسندگان
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