کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10768843 1050816 2005 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E−/− mice
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Depressed glutathione synthesis precedes oxidative stress and atherogenesis in Apo-E−/− mice
چکیده انگلیسی
Glutathione is a vital intracellular antioxidant. The enzymes involved in its synthesis and utilisation are tightly regulated, but the importance of glutathione regulation in atherogenesis is poorly understood. Here, we establish that glutathione is severely (∼80%) depleted very early (10 weeks) in the atheroma-prone aortic arch of male apoprotein E-deficient (Apo-E−/−) mice compared to age-matched wild-type controls. Importantly, this event pre-empts lipid peroxidation and detectable atheroma by several months. Depletion of glutathione was associated with excessive oxidant burden and reduced transcription and activity of the rate-limiting enzyme for glutathione synthesis, γ-glutamylcysteine ligase, together with the glutathione-dependent antioxidant enzyme, glutathione peroxidase. Depletion via reduced synthesis of glutathione precedes lipid peroxidation and atherogenesis in Apo-E−/− mice. We suggest that glutathione deficiency is central to the failure of the intracellular antioxidant defences and is causally implicated in the pathogenesis of atherosclerosis. Modification of the glutathione pathway may present a novel and important therapeutic target in the prevention and treatment of atherosclerosis.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 338, Issue 3, 23 December 2005, Pages 1368-1373
نویسندگان
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