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

Kaviarasan Subramanian, Vishal D. Naik, Kunju Sathishkumar, Onkar B. Sawant, Shannon E. Washburn, Guoyao Wu, Chandra Yallampalli, George R. Saade, Gary D. Hankins, Jayanth Ramadoss

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

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 (↓P=0.016) and ATP (↑P<0.001). Alcohol decreased Pthr495eNOS (P=0.004) levels, whereas inhibitory Pser116eNOS exhibited an alcohol main effect in both basal and stimulated states (↑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 (↓P=0.031) and glutathione-S-transferase (↓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.

Original languageEnglish (US)
Pages (from-to)94-101
Number of pages8
JournalReproductive Toxicology
Volume43
DOIs
StatePublished - Jan 1 2014

Keywords

  • ATP
  • ENOS
  • Endothelium
  • FASD
  • Vascular

ASJC Scopus subject areas

  • Toxicology

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