Thrombin-induced oxidative stress contributes to the death of hippocampal neurons: Role of neuronal NADPH oxidase
| Autor: | Byung K. Jin, Keun W. Park |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
Neurotoxins
Hippocampal formation Protein oxidation medicine.disease_cause Hippocampus Antioxidants Rats Sprague-Dawley Cellular and Molecular Neuroscience Thrombin medicine Animals Neurotoxin Enzyme Inhibitors Cells Cultured Neurons NADPH oxidase Cell Death Dose-Response Relationship Drug biology Neurodegeneration Neurotoxicity NADPH Oxidases Phosphoproteins medicine.disease Molecular biology Rats Oxidative Stress Nerve Degeneration biology.protein Heredodegenerative Disorders Nervous System Female Reactive Oxygen Species Oxidative stress medicine.drug |
| Zdroj: | Journal of Neuroscience Research. 86:1053-1063 |
| ISSN: | 1097-4547 0360-4012 |
| Popis: | The present study investigated whether thrombin can induce the production of reactive oxygen species (ROS) through activation of neuronal NADPH oxidase and whether this contributes to oxidative damage and consequently to neurodegeneration. Immunocytochemical and biochemical evidence demonstrated that, in neuron-enriched hippocampal cultures, thrombin induces neurodegeneration in a dose-dependent manner. In parallel, ROS production was evident as assessed by analyzing DCF and hydroethidine. Real-time PCR analysis, at various time points after thrombin treatment, also demonstrated that expression of NADPH oxidase subunits (p47phox and p67phox) occurs. In addition, Western blot analysis and double-label immunocytochemistry showed an up-regulation in the expression of cytosolic components (Rac 1 and p67phox), the translocation of cytosolic proteins (p47phox and p67phox) to the membrane, and the localization of gp91phox or p47phox expression in hippocampal neurons of cultures and CA1 layer. The thrombin-induced ROS production, protein oxidation, and loss of cultured hippocampal neurons were partially attenuated by an NADPH oxidase inhibitor and/or by several antioxidants. Collectively, the present study is the first to demonstrate that, in cultured hippocampal neurons, thrombin-induced neurotoxicity is, at least in part, caused by neuronal NADPH oxidase-mediated oxidative stress. This strongly suggests that thrombin can act as an endogenous neurotoxin, and inhibitors of thrombin and/or antioxidants can be useful agents for treating oxidative stress-mediated hippocampal neurodegenerative diseases, such as Alzheimer's disease. © 2008 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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