title: Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart.
abstract: Administration of low-dose endotoxin (lipopolysaccharide, LPS) 24 h before a lethal ischemia induces pharmacological late preconditioning. The exact mechanism of this phenomenon is not clear. Here we aimed to investigate whether low-dose LPS exerts late effects on peroxynitrite formation and activation of Akt, Erk, and STAT3 in the heart. Male Wistar rats were injected with LPS (S. typhimurium; 0.5 mg/kg i.p.) or saline. Twenty-four hours later, hearts were isolated, perfused for 10 min, and then used for biochemical analyses. LPS pretreatment enhanced cardiac formation of the peroxynitrite marker 3-nitrotyrosine. LPS pretreatment also increased cardiac levels of the peroxynitrite precursor nitric oxide (NO) and superoxide. The activities of Ca2+-independent NO synthase and xanthine oxidoreductase increased in LPS-pretreated hearts. LPS pretreatment resulted in significantly enhanced phosphorylation of STAT3 and non-significantly increased phosphorylation of Akt without affecting the activation of Erk. In separate experiments, isolated working hearts were subjected to 30 min global ischemia and 20 min reperfusion. LPS pretreatment significantly improved ischemia-reperfusion-induced deterioration of cardiac function. We conclude that LPS pretreatment enhances cardiac peroxynitrite formation and activates STAT3 24 h later, which may contribute to LPS-induced late preconditioning.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. pipicz.marton@med.u-szeged.hu.
authors.forename: Márton
authors.initials: M
authors.lastname: Pipicz
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. gokf1@leicester.ac.uk.
authors.forename: Gabriella F
authors.initials: GF
authors.lastname: Kocsis
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary.
authors.forename: László
authors.initials: L
authors.lastname: Sárváry-Arantes
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. bencsik.peter@med.u-szeged.hu.|Pharmahungary 2000 Ltd., Dóm tér. 9., H-6720 Szeged, Hungary. bencsik.peter@med.u-szeged.hu.
authors.forename: Péter
authors.initials: P
authors.lastname: Bencsik
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. varga.zoltan@med.semmelweis-univ.hu.|Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér. 4., H-1089 Budapest, Hungary. varga.zoltan@med.semmelweis-univ.hu.
authors.forename: Zoltán V
authors.initials: ZV
authors.lastname: Varga
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. peter.ferdinandy@pharmahungary.com.|Pharmahungary 2000 Ltd., Dóm tér. 9., H-6720 Szeged, Hungary. peter.ferdinandy@pharmahungary.com.|Department of Pharmacology and Pharmacotherapy, Semmelweis University, Nagyvárad tér. 4., H-1089 Budapest, Hungary. peter.ferdinandy@pharmahungary.com.
authors.forename: Péter
authors.initials: P
authors.lastname: Ferdinandy
authors.affiliation: Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, Hungary. csont.tamas@med.u-szeged.hu.
authors.forename: Tamás
authors.initials: T
authors.lastname: Csont
mesh_terms: D000818:Animals; D004731:Endotoxins / Q000008:administration & dosage*; D019157:Ischemic Preconditioning, Myocardial; D045022:Lactate Dehydrogenases / Q000378:metabolism; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000096:biosynthesis*; D051381:Rats; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D050796:STAT3 Transcription Factor; D030421:Peroxynitrous Acid; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine; D045022:Lactate Dehydrogenases; D019001:Nitric Oxide Synthase
keywords: ONOO−; SAFE pathway; XOR; cardioprotection; iNOS; oxidative stress