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Nur77 attenuates inflammatory responses and oxidative stress by inhibiting phosphorylated I?B-? in Parkinson's disease cell model.


ABSTRACT: Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Silencing Nur77 with siRNA can aggravate intracellular LDH release, increase the expression of pro-inflammatory genes (such as tumor necrosis factor ?, nuclear factor ?B (p65), monocyte chemotactic protein 1, interleukin-6), and decrease cell survival, decrease expression of nuclear factor E2-related factor(Nrf2), heme oxygenase 1, NADPH quinineoxidoreductase-1. Cytosporone B (Nur77 agonist) has the opposite effect to Nur77 silencing. PDTC (NF-?B inhibitor / antioxidant) can also inhibit pro-inflammatory genes to a similar degree as Cytosporone B. Phosphorylated I?B-? can be inhibited by Cytosporone B, while silencing Nur77 can increase the protein expression level of phosphorylated I?B-?. After silencing I?B-?, both Cytosporone B and siNur77 did not affect pro-inflammatory genes and antioxidant stress. These findings reveal the first evidence that Nur77 exerts anti-inflammatory and antioxidant stress effects by inhibiting I?B-? phosphorylation expression in a Parkinson cell model. Nur77 may be a potential therapeutic target for Parkinson's disease.

SUBMITTER: Yan J 

PROVIDER: S-EPMC7244064 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Nur77 attenuates inflammatory responses and oxidative stress by inhibiting phosphorylated IκB-α in Parkinson's disease cell model.

Yan Junqiang J   Huang Jiarui J   Wu Jiannan J   Fan Hua H   Liu Anran A   Qiao Liang L   Shen Mengmeng M   Lai Xiaoyi X  

Aging 20200513 9


Neuroinflammation and oxidative stress play key roles in the pathological development of Parkinson's disease (PD). Nerve growth factor-induced gene B (Nur77) is closely related to dopamine neurotransmission, and its pathogenesis is unclear. This study aims to investigate the role and mechanism of Nur77 in a cell model of Parkinson's disease. Silencing Nur77 with siRNA can aggravate intracellular LDH release, increase the expression of pro-inflammatory genes (such as tumor necrosis factor α, nucl  ...[more]

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