Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation
•Chronic in vitro binge alcohol exposure dysregulates the exquisite coordination and regulation of umbilical endothelial vascular adaptations.•Binge-like alcohol has detrimental effects on all four major eNOS multi-site phosphorylation sites.•There is an interactive effect of alcohol and the endogen...
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| Veröffentlicht in: | Reproductive toxicology (Elmsford, N.Y.) N.Y.), 2014-01, Vol.43, p.94-101 |
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| creator | 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 |
| description | •Chronic in vitro binge alcohol exposure dysregulates the exquisite coordination and regulation of umbilical endothelial vascular adaptations.•Binge-like alcohol has detrimental effects on all four major eNOS multi-site phosphorylation sites.•There is an interactive effect of alcohol and the endogenous eNOS activating agonist ATP on eNOS multi-site phosphorylation state.•Alcohol modulates eNOS-related redox switch post-translational modifications.•Major role for the reproductive vascular system in pathogenesis of Fetal Alcohol Spectrum Disorders.
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 |
| doi_str_mv | 10.1016/j.reprotox.2013.11.006 |
| format | Article |
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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.</description><identifier>ISSN: 0890-6238</identifier><identifier>EISSN: 1873-1708</identifier><identifier>DOI: 10.1016/j.reprotox.2013.11.006</identifier><identifier>PMID: 24300283</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adenosine Triphosphate - pharmacology ; ATP ; Binge Drinking - metabolism ; Cells, Cultured ; Endothelium ; eNOS ; Ethanol - pharmacology ; FASD ; Glutathione - metabolism ; Glutathione Disulfide - metabolism ; Human Umbilical Vein Endothelial Cells - drug effects ; Human Umbilical Vein Endothelial Cells - metabolism ; Humans ; Nitric Oxide Synthase Type III - metabolism ; Oxidation-Reduction ; Protein Processing, Post-Translational - drug effects ; Umbilical Cord - metabolism ; Vascular</subject><ispartof>Reproductive toxicology (Elmsford, N.Y.), 2014-01, Vol.43, p.94-101</ispartof><rights>2013 Elsevier Inc.</rights><rights>Copyright © 2013 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c471t-f87f58580de946b2e423381fd2a25cdaf197b3d9b9132f339d430d68983779493</citedby><cites>FETCH-LOGICAL-c471t-f87f58580de946b2e423381fd2a25cdaf197b3d9b9132f339d430d68983779493</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S089062381300381X$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,776,780,881,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24300283$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Subramanian, Kaviarasan</creatorcontrib><creatorcontrib>Naik, Vishal D.</creatorcontrib><creatorcontrib>Sathishkumar, Kunju</creatorcontrib><creatorcontrib>Sawant, Onkar B.</creatorcontrib><creatorcontrib>Washburn, Shannon E.</creatorcontrib><creatorcontrib>Wu, Guoyao</creatorcontrib><creatorcontrib>Yallampalli, Chandra</creatorcontrib><creatorcontrib>Saade, George R.</creatorcontrib><creatorcontrib>Hankins, Gary D.</creatorcontrib><creatorcontrib>Ramadoss, Jayanth</creatorcontrib><title>Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation</title><title>Reproductive toxicology (Elmsford, N.Y.)</title><addtitle>Reprod Toxicol</addtitle><description>•Chronic in vitro binge alcohol exposure dysregulates the exquisite coordination and regulation of umbilical endothelial vascular adaptations.•Binge-like alcohol has detrimental effects on all four major eNOS multi-site phosphorylation sites.•There is an interactive effect of alcohol and the endogenous eNOS activating agonist ATP on eNOS multi-site phosphorylation state.•Alcohol modulates eNOS-related redox switch post-translational modifications.•Major role for the reproductive vascular system in pathogenesis of Fetal Alcohol Spectrum Disorders.
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.</description><subject>Adenosine Triphosphate - pharmacology</subject><subject>ATP</subject><subject>Binge Drinking - metabolism</subject><subject>Cells, Cultured</subject><subject>Endothelium</subject><subject>eNOS</subject><subject>Ethanol - pharmacology</subject><subject>FASD</subject><subject>Glutathione - metabolism</subject><subject>Glutathione Disulfide - metabolism</subject><subject>Human Umbilical Vein Endothelial Cells - drug effects</subject><subject>Human Umbilical Vein Endothelial Cells - metabolism</subject><subject>Humans</subject><subject>Nitric Oxide Synthase Type III - metabolism</subject><subject>Oxidation-Reduction</subject><subject>Protein Processing, Post-Translational - drug effects</subject><subject>Umbilical Cord - metabolism</subject><subject>Vascular</subject><issn>0890-6238</issn><issn>1873-1708</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkd1uEzEQhS0EoqHwCpVfYBd7vdm1bxBVBbRSJbgo15bXHjcTNnZkO1H6NH1VnIZWcMWVf-acMx5_hFxw1nLGh4_rNsE2xRIPbce4aDlvGRtekQWXo2j4yORrsmBSsWbohDwj73JeM8b6UY1vyVnXC8Y6KRbk8SYUSMYW3AMF78GWTKOnGOgeS4p0wnAPzYy_gJrZxlWcqQmOXt79oDHQ3WbCGa2ZKQQXywpmrPtQnWhpPKADmh9CWZkMdBtzaUoyIc-mYAxVuIkOfbUfj_kpN4GLh-P97iR6T954M2f48Gc9Jz-_frm7um5uv3-7ubq8bWw_8tJ4OfqlXErmQPXD1EHfCSG5d53pltYZz9U4CacmxUXnhVCu_oAbpJJiHFWvxDn5dMrd7qYNOAuhvnTW24Qbkx50NKj_rQRc6fu410JxJdmyBgynAJtizgn8i5czfUSm1_oZmT4i05zriqwaL_7u_GJ7ZlQFn08CqPPvEZLOFiFYcJgqLu0i_q_Hb2XesVQ</recordid><startdate>20140101</startdate><enddate>20140101</enddate><creator>Subramanian, Kaviarasan</creator><creator>Naik, Vishal D.</creator><creator>Sathishkumar, Kunju</creator><creator>Sawant, Onkar B.</creator><creator>Washburn, Shannon E.</creator><creator>Wu, Guoyao</creator><creator>Yallampalli, Chandra</creator><creator>Saade, George R.</creator><creator>Hankins, Gary D.</creator><creator>Ramadoss, Jayanth</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope></search><sort><creationdate>20140101</creationdate><title>Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c471t-f87f58580de946b2e423381fd2a25cdaf197b3d9b9132f339d430d68983779493</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Adenosine Triphosphate - pharmacology</topic><topic>ATP</topic><topic>Binge Drinking - metabolism</topic><topic>Cells, Cultured</topic><topic>Endothelium</topic><topic>eNOS</topic><topic>Ethanol - pharmacology</topic><topic>FASD</topic><topic>Glutathione - metabolism</topic><topic>Glutathione Disulfide - metabolism</topic><topic>Human Umbilical Vein Endothelial Cells - drug effects</topic><topic>Human Umbilical Vein Endothelial Cells - metabolism</topic><topic>Humans</topic><topic>Nitric Oxide Synthase Type III - metabolism</topic><topic>Oxidation-Reduction</topic><topic>Protein Processing, Post-Translational - drug effects</topic><topic>Umbilical Cord - metabolism</topic><topic>Vascular</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Subramanian, Kaviarasan</creatorcontrib><creatorcontrib>Naik, Vishal D.</creatorcontrib><creatorcontrib>Sathishkumar, Kunju</creatorcontrib><creatorcontrib>Sawant, Onkar B.</creatorcontrib><creatorcontrib>Washburn, Shannon E.</creatorcontrib><creatorcontrib>Wu, Guoyao</creatorcontrib><creatorcontrib>Yallampalli, Chandra</creatorcontrib><creatorcontrib>Saade, George R.</creatorcontrib><creatorcontrib>Hankins, Gary D.</creatorcontrib><creatorcontrib>Ramadoss, Jayanth</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Subramanian, Kaviarasan</au><au>Naik, Vishal D.</au><au>Sathishkumar, Kunju</au><au>Sawant, Onkar B.</au><au>Washburn, Shannon E.</au><au>Wu, Guoyao</au><au>Yallampalli, Chandra</au><au>Saade, George R.</au><au>Hankins, Gary D.</au><au>Ramadoss, Jayanth</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation</atitle><jtitle>Reproductive toxicology (Elmsford, N.Y.)</jtitle><addtitle>Reprod Toxicol</addtitle><date>2014-01-01</date><risdate>2014</risdate><volume>43</volume><spage>94</spage><epage>101</epage><pages>94-101</pages><issn>0890-6238</issn><eissn>1873-1708</eissn><abstract>•Chronic in vitro binge alcohol exposure dysregulates the exquisite coordination and regulation of umbilical endothelial vascular adaptations.•Binge-like alcohol has detrimental effects on all four major eNOS multi-site phosphorylation sites.•There is an interactive effect of alcohol and the endogenous eNOS activating agonist ATP on eNOS multi-site phosphorylation state.•Alcohol modulates eNOS-related redox switch post-translational modifications.•Major role for the reproductive vascular system in pathogenesis of Fetal Alcohol Spectrum Disorders.
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.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24300283</pmid><doi>10.1016/j.reprotox.2013.11.006</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Reproductive toxicology (Elmsford, N.Y.), 2014-01, Vol.43, p.94-101 |
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| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Adenosine Triphosphate - pharmacology ATP Binge Drinking - metabolism Cells, Cultured Endothelium eNOS Ethanol - pharmacology FASD Glutathione - metabolism Glutathione Disulfide - metabolism Human Umbilical Vein Endothelial Cells - drug effects Human Umbilical Vein Endothelial Cells - metabolism Humans Nitric Oxide Synthase Type III - metabolism Oxidation-Reduction Protein Processing, Post-Translational - drug effects Umbilical Cord - metabolism Vascular |
| title | Interactive effects of in vitro binge-like alcohol and ATP on umbilical endothelial nitric oxide synthase post-translational modifications and redox modulation |
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