کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2570545 1128590 2008 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Glutathione level regulates HNE-induced genotoxicity in human erythroleukemia cells
چکیده انگلیسی

4-Hydroxy-trans-2-nonenal (HNE) is one of the most abundant and toxic lipid aldehydes formed during lipid peroxidation by reactive oxygen species. We have investigated the genotoxic effects of HNE and its regulation by cellular glutathione (GSH) levels in human erythroleukemia (K562) cells. Incubation of K562 cells with HNE (5–10 μM) significantly elicited a 3- to 5-fold increased DNA damage in a time- and dose-dependent manner as measured by comet assay. Depletion of GSH in cells by l-buthionine-[S,R]-sulfoximine (BSO) significantly increased HNE-induced DNA damage, whereas supplementation of GSH by incubating the cells with GSH-ethyl ester significantly decreased HNE-induced genotoxicity. Further, overexpression of mGSTA4-4, a HNE-detoxifying GST isozyme, significantly prevented HNE-induced DNA damage in cells, and ablation of GSTA4-4 and aldose reductase with respective siRNAs further augmented HNE-induced DNA damage. These results suggest that the genotoxicity of HNE is highly dependent on cellular GSH/GST/AR levels and favorable modulation of the aldehyde detoxification system may help in controlling the oxidative stress-induced complications.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology and Applied Pharmacology - Volume 227, Issue 2, 1 March 2008, Pages 257–264
نویسندگان
, , , ,