Rho-kinase (ROCK-1 and ROCK-2) upregulation in oleic acid-induced lung injury and its restoration by Y-27632
| Autor: | Ali Özdülger, Caglar Yildirim, Kansu Büyükafşar, Murat Bayram Kaplan, Havva Kubat, Leyla Cinel, Ulas Degirmenci, Lülüfer Tamer, Rukiye Nalan Tiftik, Oguz Koksel |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Male
Pyridines Blotting Western Protein Serine-Threonine Kinases Lung injury Pharmacology Nitric oxide Random Allocation chemistry.chemical_compound Western blot Malondialdehyde medicine Animals Enzyme Inhibitors Rats Wistar Tyrosine Lung Rho-associated protein kinase Nitrites Peroxidase rho-Associated Kinases Nitrates Dose-Response Relationship Drug biology medicine.diagnostic_test Intracellular Signaling Peptides and Proteins Amides Rats Up-Regulation Oleic acid chemistry Biochemistry Myeloperoxidase Injections Intravenous biology.protein Female Oleic Acid |
| Zdroj: | European Journal of Pharmacology. 510:135-142 |
| ISSN: | 0014-2999 |
| Popis: | The possible contribution of Rho/Rho-kinase signalling in oleic acid (100 mg kg −1 , i.v., for 4 h)-induced lung injury was investigated in rats. Furthermore, the possible protective effect of the administration of a Rho-kinase inhibitor, (+)-( R )- trans -4-(1-aminoethyl)- N -(4-pyridyl) cyclohexanecarboxamide dihydrochloride monohydrate (Y-27632, 0.5–5 mg kg −1 , i.v., 15 min before the administration of oleic acid), was also examined. Western blot analysis as well as histopathological examination revealed that Rho-kinase (ROCK-1 and ROCK-2) was upregulated in lungs obtained from oleic acid-administrated rats. In addition, the markers of oxidative and nitrosative stress, i.e., malondialdehyde, myeloperoxidase, 3-nitro- l -tyrosine and nitrite/nitrate, in serum and lung tissue were also increased in the injury group. Treatment of rats with 5 mg kg −1 Y-27632 reversed the oleic acid-induced lung damage, which was demonstrated by histopathological assessment and confirmed in Western blot experiments: ROCK-blots were more intense in the oleic acid group than in control and Y-27632 treatment reversed ROCK upregulation. In addition, malondialdehyde, myeloperoxidase, 3-nitro- l -tyrosine and nitrite/nitrate were also normalized after the administration of Y-27632 (0.5 mg kg −1 and 5 mg kg −1 ). These findings suggest that ROCK-1 and ROCK-2 are involved in oleic acid-induced lung damage in rats, and that inhibition of this enzyme by Y-27632 may have a protective effect against such damage. Consequently, Rho kinase inhibitors may be potential therapeutic agents in the treatment of acute respiratory distress syndrome (ARDS). |
| Databáze: | OpenAIRE |
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