Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation

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• 作者：Kaviarasan Subramanian ; Vishal D. Naik ; Kunju Sathishkumar ; Onkar B. Sawant ; Shannon E. Washburn ; Guoyao Wu ; Ch ; ra Yallampalli ; George R. Saade ; Gary D. Hankins ; Jayanth Ramadoss
• 关键词：Endothelium ; eNOS ; ATP ; Vascular ; FASD
• 刊名：Reproductive Toxicology
• 出版年：January, 2014
• 年：2014
• 卷：43
• 期：Complete
• 页码：94-101
• 全文大小：1942 K

文摘

Alcohol dysregulates the regulation of reproductive vascular adaptations. We herein investigated chronic in vitro binge-like alcohol effects on umbilical endothelial nitric oxide synthase (eNOS) multi-site phosphorylation and related redox switches under basal (unstimulated) and stimulated (with ATP) states. Alcohol decreased endothelial excitatory ^Pser1177eNOS (P < 0.001), whereas excitatory ^Pser635eNOS exhibited a main effect of alcohol (鈫?em>P = 0.016) and ATP (鈫?em>P < 0.001). Alcohol decreased ^Pthr495eNOS (P = 0.004) levels, whereas inhibitory ^Pser116eNOS exhibited an alcohol main effect in both basal and stimulated states (鈫?em>P = 0.005). Total eNOS was reduced by alcohol (P = 0.038). In presence of ATP, alcohol inhibited ERK activity (P = 0.002), whereas AKT exhibited no alcohol effect. Alcohol main effect on S-nitroso-glutathione reductase (鈫?em>P = 0.031) and glutathione-S-transferase (鈫?em>P = 0.027) were noted. Increased protein glutathiolation was noted, whereas no alcohol effect on GSH, GSSG, NOX2 or SOD expression was noted. Thus, alcohol effects on multi-site post-translational modifications and redox switches related to vasodilatory eNOS underscore the necessity for investigating alcohol-induced gestational vascular dysfunction.