title: Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation.
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.
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Kaviarasan
authors.initials: K
authors.lastname: Subramanian
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Vishal D
authors.initials: VD
authors.lastname: Naik
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Kunju
authors.initials: K
authors.lastname: Sathishkumar
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors.forename: Onkar B
authors.initials: OB
authors.lastname: Sawant
authors.affiliation: Department of Physiology and Pharmacology, Texas A&M University, College Station, TX, USA.
authors.forename: Shannon E
authors.initials: SE
authors.lastname: Washburn
authors.affiliation: Department of Animal Sciences, Texas A&M University, College Station, TX, USA.
authors.forename: Guoyao
authors.initials: G
authors.lastname: Wu
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Chandra
authors.initials: C
authors.lastname: Yallampalli
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Saade
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Gary D
authors.initials: GD
authors.lastname: Hankins
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Medical Branch, Galveston, TX, USA. Electronic address: jaramado@utmb.edu.
authors.forename: Jayanth
authors.initials: J
authors.lastname: Ramadoss
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D063425:Binge Drinking / Q000378:metabolism; D002478:Cells, Cultured; D000431:Ethanol / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014470:Umbilical Cord / Q000378:metabolism
chemical_list: D000431:Ethanol; D000255:Adenosine Triphosphate; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; D005978:Glutathione; D019803:Glutathione Disulfide
keywords: ATP; Endothelium; FASD; Vascular; eNOS