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 Saade, Gary Hankins, Jayanth Ramadoss

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 2014

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Umbilicus
Nitric Oxide Synthase Type III
Post Translational Protein Processing
Oxidation-Reduction
Adenosine Triphosphate
Alcohols
Modulation
In Vitro Techniques
Blood Vessels
Switches
Phosphorylation
Glutathione Disulfide
Glutathione Reductase
Glutathione Transferase

Keywords

  • ATP
  • Endothelium
  • ENOS
  • FASD
  • Vascular

ASJC Scopus subject areas

  • Toxicology

Cite this

Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation. / Subramanian, Kaviarasan; Naik, Vishal D.; Sathishkumar, Kunju; Sawant, Onkar B.; Washburn, Shannon E.; Wu, Guoyao; Yallampalli, Chandra; Saade, George; Hankins, Gary; Ramadoss, Jayanth.

In: Reproductive Toxicology, Vol. 43, 01.2014, p. 94-101.

Research output: Contribution to journalArticle

Subramanian, Kaviarasan ; Naik, Vishal D. ; Sathishkumar, Kunju ; Sawant, Onkar B. ; Washburn, Shannon E. ; Wu, Guoyao ; Yallampalli, Chandra ; Saade, George ; Hankins, Gary ; Ramadoss, Jayanth. / Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation. In: Reproductive Toxicology. 2014 ; Vol. 43. pp. 94-101.
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