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Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart.
- Source :
-
Molecules (Basel, Switzerland) [Molecules] 2017 Mar 08; Vol. 22 (3). Date of Electronic Publication: 2017 Mar 08. - Publication Year :
- 2017
-
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.
- Subjects :
- Animals
Lactate Dehydrogenases metabolism
Lipopolysaccharides administration & dosage
Male
Nitric Oxide metabolism
Nitric Oxide Synthase metabolism
Oxidation-Reduction
Rats
Tyrosine analogs & derivatives
Tyrosine biosynthesis
Endotoxins administration & dosage
Ischemic Preconditioning, Myocardial
Myocardial Ischemia metabolism
Peroxynitrous Acid biosynthesis
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1420-3049
- Volume :
- 22
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Molecules (Basel, Switzerland)
- Publication Type :
- Academic Journal
- Accession number :
- 28282895
- Full Text :
- https://doi.org/10.3390/molecules22030433