Article: L-arginine enhances nitrative stress and exacerbates tumor necrosis factor-α toxicity to human endothelial cells in culture: Prevention by propofol

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TitleL-arginine enhances nitrative stress and exacerbates tumor necrosis factor-α toxicity to human endothelial cells in culture: Prevention by propofol
AuthorsXia, Z1 3
Luo, T1
Liu, HM1 3
Wang, F1
Xia, ZY1
Irwin, MG3
Vanhoutte, PM2 3
KeywordsApoptosis
L-arginine
Nitrative stress
Propofol
Tumor necrosis factor-a
Issue Date2010
PublisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/
CitationJournal Of Cardiovascular Pharmacology, 2010, v. 55 n. 4, p. 358-367 [How to Cite?]
DOI: http://dx.doi.org/10.1097/FJC.0b013e3181d265a3
AbstractSupplementation of L-arginine, a nitric oxide precursor, during the late phase of myocardial ischemia/reperfusion increases myocyte apoptosis and exacerbates myocardial injury, but the underlying mechanism is unclear. During myocardial ischemia/reperfusion, apoptosis of endothelial cells precedes that of cardiomyocyte. Tumor necrosis factor-α (TNF) production is increased during myocardial ischemia/reperfusion, which may exacerbate myocardial injury by inducing endothelial cell apoptosis. We postulated that L-arginine may exacerbate TNF-induced endothelial cell apoptosis by enhancing peroxynitrite-mediated nitrative stress. Cultured human umbilical vein endothelial cells were either not treated (control) or treated with TNF alone or with TNF in the presence of L-arginine, the nonselective nitric oxide synthase inhibitor N (omega)-nitro-L-arginine (L-NNA), propofol (an anesthetic that scavenges peroxynitrite), or L-arginine plus propofol, respectively, for 24 hours. TNF increased intracellular superoxide and hydrogen peroxide production accompanied by increases of inducible nitric oxide synthase (iNOS) protein expression and nitric oxide production. This was accompanied by increased protein expression of nitrotyrosine, a fingerprint of peroxynitrite and an index of nitrative stress, and increased endothelial cell apoptosis. L-arginine did not enhance TNF-induced increases of superoxide and peroxynitrite production but further increased TNF-induced increase of nitrotyrosine production and exacerbated TNF-mediated cell apoptosis. L-NNA and propofol, respectively, reduced TNF-induced nitrative stress and attenuated TNF cellular toxicity. The L-arginine-mediated enhancement of nitrative stress and TNF toxicity was attenuated by propofol. Thus, under pathological conditions associated with increased TNF production, L-arginine supplementation may further exacerbate TNF cellular toxicity by enhancing nitrative stress. © 2010 by Lippincott Williams & Wilkins.
ISSN0160-2446
2011 Impact Factor: 2.287
2011 SCImago Journal Rankings: 0.219
DOIhttp://dx.doi.org/10.1097/FJC.0b013e3181d265a3
ISI Accession Number IDWOS:000277307900008
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorXia, Z
dc.contributor.authorLuo, T
dc.contributor.authorLiu, HM
dc.contributor.authorWang, F
dc.contributor.authorXia, ZY
dc.contributor.authorIrwin, MG
dc.contributor.authorVanhoutte, PM
dc.date.accessioned2011-10-28T02:42:25Z
dc.date.available2011-10-28T02:42:25Z
dc.date.issued2010
dc.description.abstractSupplementation of L-arginine, a nitric oxide precursor, during the late phase of myocardial ischemia/reperfusion increases myocyte apoptosis and exacerbates myocardial injury, but the underlying mechanism is unclear. During myocardial ischemia/reperfusion, apoptosis of endothelial cells precedes that of cardiomyocyte. Tumor necrosis factor-α (TNF) production is increased during myocardial ischemia/reperfusion, which may exacerbate myocardial injury by inducing endothelial cell apoptosis. We postulated that L-arginine may exacerbate TNF-induced endothelial cell apoptosis by enhancing peroxynitrite-mediated nitrative stress. Cultured human umbilical vein endothelial cells were either not treated (control) or treated with TNF alone or with TNF in the presence of L-arginine, the nonselective nitric oxide synthase inhibitor N (omega)-nitro-L-arginine (L-NNA), propofol (an anesthetic that scavenges peroxynitrite), or L-arginine plus propofol, respectively, for 24 hours. TNF increased intracellular superoxide and hydrogen peroxide production accompanied by increases of inducible nitric oxide synthase (iNOS) protein expression and nitric oxide production. This was accompanied by increased protein expression of nitrotyrosine, a fingerprint of peroxynitrite and an index of nitrative stress, and increased endothelial cell apoptosis. L-arginine did not enhance TNF-induced increases of superoxide and peroxynitrite production but further increased TNF-induced increase of nitrotyrosine production and exacerbated TNF-mediated cell apoptosis. L-NNA and propofol, respectively, reduced TNF-induced nitrative stress and attenuated TNF cellular toxicity. The L-arginine-mediated enhancement of nitrative stress and TNF toxicity was attenuated by propofol. Thus, under pathological conditions associated with increased TNF production, L-arginine supplementation may further exacerbate TNF cellular toxicity by enhancing nitrative stress. © 2010 by Lippincott Williams & Wilkins.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationJournal Of Cardiovascular Pharmacology, 2010, v. 55 n. 4, p. 358-367 [How to Cite?]
DOI: http://dx.doi.org/10.1097/FJC.0b013e3181d265a3
dc.identifier.doihttp://dx.doi.org/10.1097/FJC.0b013e3181d265a3
dc.identifier.epage367
dc.identifier.hkuros184516
dc.identifier.hkuros171203
dc.identifier.isiWOS:000277307900008
dc.identifier.issn0160-2446
2011 Impact Factor: 2.287
2011 SCImago Journal Rankings: 0.219
dc.identifier.issue4
dc.identifier.openurl
dc.identifier.pmid20125033
dc.identifier.scopuseid_2-s2.0-77951742414
dc.identifier.spage358
dc.identifier.urihttp://hdl.handle.net/10722/142303
dc.identifier.volume55
dc.languageeng
dc.publisherLippincott Williams & Wilkins. The Journal's web site is located at http://www.cardiovascularpharm.com/
dc.publisher.placeUnited States
dc.relation.ispartofJournal of Cardiovascular Pharmacology
dc.relation.referencesReferences in Scopus
dc.subject.meshApoptosis - drug effects
dc.subject.meshArginine - pharmacology
dc.subject.meshOxidative Stress - drug effects
dc.subject.meshPropofol - pharmacology
dc.subject.meshTumor Necrosis Factor-alpha - pharmacology
dc.subjectApoptosis
dc.subjectL-arginine
dc.subjectNitrative stress
dc.subjectPropofol
dc.subjectTumor necrosis factor-a
dc.titleL-arginine enhances nitrative stress and exacerbates tumor necrosis factor-α toxicity to human endothelial cells in culture: Prevention by propofol
dc.typeArticle
Author Affiliations
  1. Hubei General Hospital
  2. Chonbuk National University
  3. The University of Hong Kong