Contribution Of Rhoa/Rho-Kinase/Mek1/Erk1/2/Inos Pathway To Ischemia/Reperfusion-Induced Oxidative/Nitrosative Stress And Inflammation Leading To Distant And Target Organ Injury In Rats
| Autor: | Bahar Tunctan, C. Kemal Buharalioglu, Necmiye Canacankatan, Lülüfer Tamer Gümüş, Aysegul Gorur, Belma Korkmaz, Meltem Kacan, Tuba Cuez, Seyhan Şahan Fırat, Nehir Sucu, Özden Vezir, Lokman Ayaz, Demet Unsal, A. Nihal Sari |
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| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty RHOA MAP Kinase Signaling System Pyridines MAP Kinase Kinase 1 Nitric Oxide Synthase Type II Inflammation Hindlimb medicine.disease_cause Kidney chemistry.chemical_compound Internal medicine Malondialdehyde Peroxynitrous Acid medicine Animals Rats Wistar Muscle Skeletal Peroxidase Pharmacology rho-Associated Kinases NADPH oxidase biology Superoxide Dismutase Nitrotyrosine NADPH Oxidases Anatomy medicine.disease Catalase Amides Glutathione Rats Oxidative Stress Endocrinology chemistry Reperfusion Injury biology.protein Tyrosine medicine.symptom rhoA GTP-Binding Protein Reperfusion injury Peroxynitrite Oxidative stress |
| Popis: | The small G protein RhoA and its downstream effector Rho-kinase play an important role in various physiopathological processes including ischemia/reperfusion (I/R) injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase are important mediators of inflammation and organ injury following an initial localized I/R event. The aim of this study was to determine whether RhoA/Rho-kinase signaling pathway increases the expression and activity of MEK1, ERK1/2, iNOS, gp91(phox), and p47(phox), and peroxynitrite formation which result in oxidative/nitrosative stress and inflammation leading to hindlimb PR-induced injury in kidney as a distant organ and;,gastrocnemius muscle as a target organ. I/R-induced distant and target organ injury was performed by using the rat hindlimb tourniquet model, I/R caused an increase in the expression and/or activity of RhoA, MEK1, ERK1/2, iNOS, gp91(phox), p47(phox), and 3-nitrotyrosine and nitrotyrosine levels in the tissues. Although Rho-kinase activity was increased by I/R in the kidney, its activity was decreased in the muscle. Serum and tissue MDA levels and MPO activity were increased following I/R. PR also caused an increase in SOD and catalase activities associated with decreased GSH levels in the tissues. Y-27632, a selective Rho-kinase inhibitor, (100 mu g/kg, i.p.; 1 h before reperfusion) prevented the I/R-induced changes except Rho-kinase activity in the muscle. These results suggest that activation of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway associated with oxidative/nitrosative stress and inflammation contributes to hindlimb PR-induced distant organ injury in rats. It also seems that hindlimb I/R induces target organ injury via upregulation of RhoA/MEK1/ERK1/2/iNOS pathway associated with decreased Rho-kinase activity. (C) 2013 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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