title: TGF-beta(1) modulates NOS expression and phosphorylation of Akt/PKB in rat myocytes exposed to hypoxia-reoxygenation.
abstract: Myocardial hypoxia-reoxygenation (H-R) is associated with upregulation of inducible nitric oxide synthase (iNOS), decrease in endothelial NOS (eNOS), and increase in protein kinase B (PKB). Previous work also shows that transforming growth factor-beta(1) (TGF-beta(1)) can attenuate myocardial injury induced by H-R. We examined the modulation of NOS and PKB expression in response to H-R by TGF- beta(1). Myocytes from Sprague-Dawley rat hearts were cultured and exposed to hypoxia (95% N(2)-5% CO(2), PO(2) ~30 mmHg) for 24 h and reoxygenation (95% air-5% CO(2)) for 3 h. Myocytes were then examined for lactate dehydrogenase (LDH) release, iNOS activity (conversion of L-[(3)H]arginine to L-[(3)H]citrulline), iNOS and eNOS expression, and PKB phosphorylation. H-R alone resulted in myocyte injury, upregulation of iNOS activity and expression, decrease in eNOS expression, and increase in PKB phosphorylation (all P < 0.05 vs. cells cultured in normoxic conditions). Treatment of myocytes with TGF-beta(1) (1 ng/ml) resulted in a reduction in LDH release, attenuation of the alterations in NOS expression (both iNOS and eNOS), and PKB phosphorylation in response to H-R (all P < 0.05 vs. H-R alone). These observations suggest that TGF-beta(1) decreases H-R injury and attenuates alterations in NOS and PKB phosphorylation in myocytes exposed to H-R.
authors.affiliation: Department of Medicine and Physiology, University of Arkansas and Central Arkansas Veterans Health Care System, Little Rock, Arkansas 72205-7199, USA.
authors.forename: H
authors.initials: H
authors.lastname: Chen
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.forename: T
authors.initials: T
authors.lastname: Saldeen
authors.forename: J L
authors.initials: JL
authors.lastname: Mehta
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017207:Rats, Sprague-Dawley; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D011518:Proto-Oncogene Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; C494920:Akt1 protein, rat; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D010100:Oxygen