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- Title
Microglial peroxiredoxin V acts as an inducible anti-inflammatory antioxidant through cooperation with redox signaling cascades.
- Authors
Hu-Nan Sun; Sun-Uk Kim; Song MeI Huang; Jin-Man Kim; Young-Ho ParK; Seok-Ho Kim; Hee-Young Yang; Kyoung-Jin Chung; Tae-Hoon Lee; Hoon Sung Choi; Ju Sik Min; Moon-Ki Park; Sang-Keun Kim; Sang-Rae Lee; Kyu-Tae Chang; Sang-Ho Lee; Dae-Yeul Yu; Dong-Seok Lee
- Abstract
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.
- Subjects
MICROGLIA; ANTIOXIDANTS; OXIDATION-reduction reaction; REACTIVE oxygen species; FREE radicals; POLYSACCHARIDES; NITRIC oxide
- Publication
Journal of Neurochemistry, 2010, Vol 114, Issue 1, p39
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2010.06691.x