TY - JOUR
T1 - Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation
AU - Subramanian, Kaviarasan
AU - Naik, Vishal D.
AU - Sathishkumar, Kunju
AU - Sawant, Onkar B.
AU - Washburn, Shannon E.
AU - Wu, Guoyao
AU - Yallampalli, Chandra
AU - Saade, George R.
AU - Hankins, Gary D.
AU - Ramadoss, Jayanth
PY - 2014/1
Y1 - 2014/1
N2 - 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.
AB - 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.
KW - ATP
KW - ENOS
KW - Endothelium
KW - FASD
KW - Vascular
UR - https://www.scopus.com/pages/publications/84890833665
UR - https://www.scopus.com/pages/publications/84890833665#tab=citedBy
U2 - 10.1016/j.reprotox.2013.11.006
DO - 10.1016/j.reprotox.2013.11.006
M3 - Article
C2 - 24300283
AN - SCOPUS:84890833665
SN - 0890-6238
VL - 43
SP - 94
EP - 101
JO - Reproductive Toxicology
JF - Reproductive Toxicology
ER -