کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2166842 1091895 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
High glucose-induced apoptosis through store-operated calcium entry and calcineurin in human umbilical vein endothelial cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
High glucose-induced apoptosis through store-operated calcium entry and calcineurin in human umbilical vein endothelial cells
چکیده انگلیسی

Diabetes mellitus causes multiple cardiovascular complications. Previous studies have shown that prolonged exposure (96 h) of human umbilical vein endothelial cells (HUVECs) to hyperglycemia causes a significant increase in apoptosis. We report here that this increase in apoptosis is associated with an increase in Ca2+ current (whole cell patch-clamp recorded) resulting from Ca2+ entry mediated by store-operated channels (SOCs). The number of apoptotic cells after prolonged high glucose (HG, 30 mmol/L) exposure was significantly reduced in the presence of the SOC inhibitor 2-APB or of La3+. A marked increase (∼80%) in Ca2+-dependent calcineurin (CN-A) phosphatase activity also occurred after prolonged HG exposure. Prolonged HG exposure-induced increase in CN-A activity was prevented by 2-APB, and selective CN-A phosphatase inhibition by FK506 or calmodulin inhibition by calmidazolium decreased HG-induced apoptosis. Blocking hydrogen peroxide production using catalase or inhibiting the tyrosine kinase pp60src during prolonged exposure to HG, resulted in a marked decrease in apoptosis and was further associated with a significant reduction in CN-A phosphatase activity. The results demonstrate a significant role for Ca2+ entry in HG-induced apoptosis in HUVECs, and suggest that this role is mediated via H2O2 generation and the action of the Ca2+-activated protein phosphatase calcineurin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 39, Issue 1, January 2006, Pages 47–55
نویسندگان
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