Contribution of MEK1/ERK1/2/iNOS Pathway to Oxidative Stress and Decreased Caspase-3 Activity in Endotoxemic Rats
| Autor: | C. Kemal Buharalioglu, Abdullah T. Demiryürek, Seyhan Sahan-Firat, A. Nihal Sari, Belma Korkmaz, Bahar Tunctan, Tuba Cuez |
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| Rok vydání: | 2012 |
| Předmět: |
Male
Antioxidant Lipopolysaccharide MAP Kinase Signaling System medicine.medical_treatment Immunology MAP Kinase Kinase 1 Nitric Oxide Synthase Type II Aorta Thoracic Apoptosis Pharmacology medicine.disease_cause Antioxidants chemistry.chemical_compound Heart Rate Nitriles Butadienes medicine Animals Immunology and Allergy Enzyme Inhibitors Rats Wistar Protein kinase A Glutathione Peroxidase Mitogen-Activated Protein Kinase 3 biology Caspase 3 Superoxide Dismutase Kinase Thiourea General Medicine Endotoxemia Enzyme assay Rats Endotoxins Nitric oxide synthase Oxidative Stress Glutathione Reductase Biochemistry chemistry biology.protein Oxidative stress |
| Zdroj: | Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry. 11:243-252 |
| ISSN: | 1871-5230 |
| DOI: | 10.2174/1871523011202030243 |
| Popis: | Oxidative stress and apoptosis are the states that can contribute to the pathogenesis of sepsis. In this study we aimed to investigate whether mitogen-activated protein kinase kinase 1 (MEK1)/extracellular signal-regulated kinase 1/2 (ERK1/2)/inducible nitric oxide synthase (iNOS) pathway plays a role in oxidative stress and apoptosis in endotoxemic rats. Systemic total antioxidant, SOD, GPx, and GR activities as markers of oxidative stress, and tissue caspase-3 enzyme activity as a marker of apoptosis were measured in sera and thoracic aortae of male Wistar rats sacrificed 4 h after being treated with saline (vehicle) or lipopolysaccharide (LPS) (10 mg/kg, i.p.). A decrease in total antioxidant activity and caspase-3, SOD, GPx, and GR enzyme activities was occured by LPS. These changes caused by LPS were prevented when a selective iNOS inhibitor, 1,3-PBIT (10 mg/kg, i.p.) or a selective inhibitor of ERK1/2 phosphorylation by MEK1, U0126 (5 mg/kg, i.p.) were given 1 h after administration of LPS. Our results suggest that decreased activity of MEK1/ERK1/2/iNOS pathway prevents oxidative stress by increasing systemic antioxidant enzyme activities and restores decreased caspase-3 activity in thoracic aorta in endotoxemic rat. |
| Databáze: | OpenAIRE |
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