کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5558929 1561231 2016 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Carbon monoxide releasing molecule induces endothelial nitric oxide synthase activation through a calcium and phosphatidylinositol 3-kinase/Akt mechanism
ترجمه فارسی عنوان
مولکول آزاد سازی مونوکسید کربن باعث فعال سازی سنتاز نیتریک اکسید اندوتلیال از طریق مکانیسم کلسیم و فسفاتیدیلینواستیل 3-کیناز / آکت
کلمات کلیدی
مونوکسید کربن، سنتاز اکسید نیتریک اندوتلیال، کلسیم، آکت،
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
چکیده انگلیسی

The production of nitric oxide (NO) by endothelial NO synthase (eNOS) plays a major role in maintaining vascular homeostasis. This study elucidated the potential role of carbon monoxide (CO)-releasing molecules (CORMs) in NO production and explored the underlying mechanisms in endothelial cells. We observed that 25 μM CORM-2 could increase NO production and stimulate an increase in the intracellular Ca2 + level. Furthermore, ethylene glycol-bis(β-aminoethyl ether)-N,N,N′,N′-tetra acetic acid caused CORM-2-induced NO production, which was abolished by 1,2-bis(2-aminophenoxy) ethane-N,N,N′,N′-tetraacetic acid tetraacetoxy-methyl ester (BAPTA-AM), indicating that intracellular Ca2 + release plays a major role in eNOS activation. The inhibition of the IP3 receptor diminished the CORM-2-induced intracellular Ca2 + increase and NO production. Furthermore, CORM-2 induced eNOS Ser1179 phosphorylation and eNOS dimerization, but it did not alter eNOS expression. CORM-2 (25 μM) also prolonged Akt phosphorylation, lasting for at least 12 h. Pretreatment with phosphatidylinositol 3-kinase inhibitors (wortmannin or LY294002) inhibited the increases in NO production and phosphorylation but did not affect eNOS dimerization. CORM-2-induced eNOS Ser1179 phosphorylation was intracellularly calcium-dependent, because pretreatment with an intracellular Ca2 + chelator (BAPTA-AM) inhibited this process. Although CORM-2 increases intracellular reactive oxygen species (ROS), pretreatment with antioxidant enzyme catalase and N-acetyl-cysteine did not abolish the CORM-2-induced eNOS activity or phosphorylation, signifying that ROS is not involved in this activity. Hence, CORM-2 enhances eNOS activation through intracellular calcium release, Akt phosphorylation, and eNOS dimerization.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Vascular Pharmacology - Volume 87, December 2016, Pages 209-218
نویسندگان
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