Journal of neurochemistry, 2010-07, Vol.114 (1), p.39-50
2010
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- Autor(en) / Beteiligte
- Titel
- Microglial peroxiredoxin V acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades
- Ist Teil von
- Journal of neurochemistry, 2010-07, Vol.114 (1), p.39-50
- Ort / Verlag
- Oxford, UK: Oxford, UK : Blackwell Publishing Ltd
- Erscheinungsjahr
- 2010
- Quelle
- Electronic Journals Library
- Beschreibungen/Notizen
- J. Neurochem. (2010) 114, 39-50. Reactive oxygen species (ROS) actively participate in microglia-mediated pathogenesis as pro-inflammatory molecules. However, little is known about the involvement of specific antioxidants in maintaining the microglial oxidative balance. We demonstrate that microglial peroxiredoxin (Prx) 5 expression is up-regulated by lipopolysaccharide (LPS) through activation of the ROS-sensitive signaling pathway and is involved in attenuation of both microglial activation and nitric oxide (NO) generation. Unlike in stimulation of oxidative insults with paraquat and hydrogen peroxide, Prx V expression is highly sensitive to LPS-stimulation in microglia. Reduction of ROS level by treatment with either NADPH oxidase inhibitor or antioxidant ablates LPS-mediated Prx V up-regulation in BV-2 microglial cells and is closely associated with the activation of the c-jun N-terminal kinase (JNK) signaling pathway. This suggests the involvement of ROS/JNK signaling in LPS-mediated Prx V induction. Furthermore, NO induces Prx V up-regulation that is ablated by the addition of inducible nitric oxide synthase inhibitor or deleted mutation of inducible nitric oxide synthase in LPS-stimulated microglia. Therefore, these results suggest that Prx V is induced by cooperative action among the ROS, RNS, and JNK signaling cascades. Interestingly, knockdown of Prx V expression causes the acceleration of microglia activation, including augmented ROS generation and JNK-dependent NO production. In summary, we demonstrate that Prx V plays a key role in the microglial activation process through modulation of the balance between ROS/NO generation and the corresponding JNK cascade activation.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-3042eISSN: 1471-4159DOI: 10.1111/j.1471-4159.2010.06691.xTitel-ID: cdi_proquest_miscellaneous_746157499
- Format
- –
- Schlagworte
- Animals, Antioxidants, Biological and medical sciences, Bones, joints and connective tissue. Antiinflammatory agents, Cell physiology, Cells, Cultured, c‐jun N‐terminal kinase, Fundamental and applied biological sciences. Psychology, Gene Knockdown Techniques, Inflammatory diseases, JNK Mitogen-Activated Protein Kinases - physiology, lipopolysaccharide, Lipopolysaccharides - pharmacology, Male, Medical sciences, Mice, Mice, Inbred ICR, microglia, Microglia - metabolism, mitogen-activated protein kinase, Molecular and cellular biology, Mutation, NADPH Oxidases - antagonists & inhibitors, NADPH Oxidases - physiology, neuroglia, nitric oxide, Nitric Oxide - biosynthesis, Nitric Oxide Synthase Type II - antagonists & inhibitors, Nitric Oxide Synthase Type II - genetics, Oxidation-Reduction, peroxiredoxin V, Peroxiredoxins - biosynthesis, Peroxiredoxins - genetics, Peroxiredoxins - physiology, Pharmacology. Drug treatments, Reaction kinetics, Reactive Nitrogen Species - metabolism, reactive oxygen species, Reactive Oxygen Species - metabolism, Signal Transduction, Up-Regulation