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

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 (Pser1177)eNOS (P<0.001), whereas excitatory (Pser635)eNOS exhibited a main effect of alcohol (↓P=0.016) and ATP (↑P<0.001). Alcohol decreased (Pthr495)eNOS (P=0.004) levels, whereas inhibitory (Pser116)eNOS 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.

published proceedings

  • Reprod Toxicol

altmetric score

  • 0.25

author list (cited authors)

  • Subramanian, K., Naik, V. D., Sathishkumar, K., Sawant, O. B., Washburn, S. E., Wu, G., ... Ramadoss, J.

citation count

  • 5

complete list of authors

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

publication date

  • January 2014