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Microglial peroxiredoxin V acts as an inducible anti‐inflammatory antioxidant through cooperation with redox signaling cascades
Author(s) -
Sun HuNan,
Kim SunUk,
Huang Song Mei,
Kim JinMan,
Park YoungHo,
Kim SeokHo,
Yang HeeYoung,
Chung KyoungJin,
Lee TaeHoon,
Choi Hoon Sung,
Min Ju Sik,
Park MoonKi,
Kim SangKeun,
Lee SangRae,
Chang KyuTae,
Lee SangHo,
Yu DaeYeul,
Lee DongSeok
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2010.06691.x
Subject(s) - microglia , microbiology and biotechnology , nadph oxidase , reactive oxygen species , peroxiredoxin , signal transduction , nitric oxide , nitric oxide synthase , chemistry , mitochondrial ros , apocynin , biology , inflammation , biochemistry , immunology , enzyme , peroxidase , organic chemistry
J. Neurochem . (2010) 114 , 39–50. Abstract 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.