title: Cardioprotective actions of an N-terminal fragment of annexin-1 in rat myocardium in vitro.
abstract: We have previously shown that the glucocorticoid dexamethasone prevents the cardiodepressant actions of interferon-gamma plus lipopolysaccharide in cardiac tissue in vitro. We now demonstrate that an N-terminal fragment of annexin-1 (Ac2-26, 1 microM), a putative mediator of glucocorticoid actions, completely protects against interferon-gamma+lipopolysaccharide-induced depression of the inotropic response to isoprenaline in rat isolated papillary muscles. However, Ac2-26 does not preserve resting contractile function. Fifteen hours incubation with interferon-gamma+lipopolysaccharide also markedly induced mRNA expression (by real time polymerase chain reaction, PCR) of both the nitric oxide synthase 2 (NOS2) isoform of nitric oxide synthase (by 6.7 +/- 1.7-fold, P < 0.01) and cyclo-oxygenase-2 (by 3.4 +/- 0.6-fold, P < 0.05) in cardiomyocytes. Pretreatment with Ac2-26 (1 microM) prevented the induction of cyclo-oxygenase-2 mRNA, but not NOS2 mRNA, whereas dexamethasone (1 microM) suppressed the expression of both NOS2 mRNA and cyclo-oxygenase-2 mRNA. Co-incubation of dexamethasone with an anti-annexin-1 antibody did not attenuate the suppression of NOS2 mRNA. Thus, Ac2-26 reproduces some, but not all, of the cardioprotective effects of glucocorticoids in vitro in the absence of neutrophils. These protective actions are independent of changes in NOS2 expression.
authors.affiliation: Howard Florey Institute and the Department of Physiology, C/- The University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Rebecca H
authors.initials: RH
authors.lastname: Ritchie
authors.forename: XiaoLu
authors.initials: X
authors.lastname: Sun
authors.forename: Justin L
authors.initials: JL
authors.lastname: Bilszta
authors.forename: Lerna M
authors.initials: LM
authors.lastname: Gulluyan
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Dusting
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000737:chemistry / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D017305:Annexin A1; D002316:Cardiotonic Agents; D007527:Isoenzymes; D008070:Lipopolysaccharides; D010446:Peptide Fragments; D012333:RNA, Messenger; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D007545:Isoproterenol