Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart
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 activat...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2017-03-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | http://www.mdpi.com/1420-3049/22/3/433 |
| _version_ | 1819109241911246848 |
|---|---|
| author | Márton Pipicz Gabriella F. Kocsis László Sárváry-Arantes Péter Bencsik Zoltán V. Varga Péter Ferdinandy Tamás Csont |
| author_facet | Márton Pipicz Gabriella F. Kocsis László Sárváry-Arantes Péter Bencsik Zoltán V. Varga Péter Ferdinandy Tamás Csont |
| author_sort | Márton Pipicz |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T03:22:42Z |
| format | Article |
| id | doaj.art-c5098fd7b9384846a1604de79c0a533e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-22T03:22:42Z |
| publishDate | 2017-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c5098fd7b9384846a1604de79c0a533e2022-12-21T18:40:42ZengMDPI AGMolecules1420-30492017-03-0122343310.3390/molecules22030433molecules22030433Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat HeartMárton Pipicz0Gabriella F. Kocsis1László Sárváry-Arantes2Péter Bencsik3Zoltán V. Varga4Péter Ferdinandy5Tamás Csont6Department of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryDepartment of Biochemistry, Faculty of Medicine, University of Szeged, Dóm tér. 9., H-6720 Szeged, HungaryAdministration 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.http://www.mdpi.com/1420-3049/22/3/433oxidative stressONOO−iNOSXORSAFE pathwaycardioprotection |
| spellingShingle | Márton Pipicz Gabriella F. Kocsis László Sárváry-Arantes Péter Bencsik Zoltán V. Varga Péter Ferdinandy Tamás Csont Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart Molecules oxidative stress ONOO− iNOS XOR SAFE pathway cardioprotection |
| title | Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart |
| title_full | Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart |
| title_fullStr | Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart |
| title_full_unstemmed | Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart |
| title_short | Low-Dose Endotoxin Induces Late Preconditioning, Increases Peroxynitrite Formation, and Activates STAT3 in the Rat Heart |
| title_sort | low dose endotoxin induces late preconditioning increases peroxynitrite formation and activates stat3 in the rat heart |
| topic | oxidative stress ONOO− iNOS XOR SAFE pathway cardioprotection |
| url | http://www.mdpi.com/1420-3049/22/3/433 |
| work_keys_str_mv | AT martonpipicz lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT gabriellafkocsis lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT laszlosarvaryarantes lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT peterbencsik lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT zoltanvvarga lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT peterferdinandy lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart AT tamascsont lowdoseendotoxininduceslatepreconditioningincreasesperoxynitriteformationandactivatesstat3intheratheart |