کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2894184 1172429 2007 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Macrophage NADPH oxidase activation, impaired cholesterol fluxes, and increased cholesterol biosynthesis in diabetic mice: A stimulatory role for d-glucose
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Macrophage NADPH oxidase activation, impaired cholesterol fluxes, and increased cholesterol biosynthesis in diabetic mice: A stimulatory role for d-glucose
چکیده انگلیسی

Diabetes is clearly associated with accelerated atherosclerosis development, but molecular mechanisms involved in diabetes-induced atherosclerosis remain to be clarified. The aim of this study was to identify cellular mechanisms involved in diabetes-induced macrophage foam cell formation, the hallmark of early atherogenesis. Mouse peritoneal macrophages (MPMs) isolated from Balb-C streptozotocin-induced diabetic mice, exhibited significantly higher total peroxides, lipid peroxides and paraoxonase 2 (PON2) activity by 290%, 61% and 55%, respectively, compared to non-diabetic mice. In vitro studies revealed that glucose-induced oxidative stress was obtained by d-glucose, but not by l-glucose and it involved activation of the NADPH oxidase complex, and up-regulation of the macrophage PON2.Next, MPMs isolated from Balb-C diabetic mice, compared to control Balb-C mice, demonstrated increased cholesterol content by 4.2-fold associated with increased cholesterol biosynthesis and increased uptake of oxidized LDL (Ox-LDL) by 5.9-fold and 31%, respectively. These effects on cellular cholesterol metabolism were associated with up-regulation of the scavenger receptors for Ox-LDL (CD-36 and SR-A), and of HMG-CoA reductase (cholesterol biosynthesis rate limiting enzyme). Finally, using pravastatin (inhibitor of HMG-CoA reductase) and the antioxidant Vitamin E, we have shown that d-glucose-induced macrophage oxidative stress is secondary to its stimulatory effect on macrophage cholesterol biosynthesis.In conclusion, macrophages from diabetic mice demonstrate increased oxidative stress associated with activation of NADPH oxidase and up-regulation of cellular PON2, as well as increased macrophages cholesterol uptake and biosynthesis (increased expression of CD-36 and HMG-CoA reductase). The above mechanisms in diabetic mice could be the result of the effect of high d-glucose on macrophages.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Atherosclerosis - Volume 195, Issue 2, December 2007, Pages 277–286
نویسندگان
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