Research Paper Volume 12, Issue 9 pp 8107—8119
Nur77 attenuates inflammatory responses and oxidative stress by inhibiting phosphorylated IκB-α in Parkinson’s disease cell model
- 1 Neurological Diseases Institute, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
- 2 Department of Neurology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
- 3 Department of Pharmacy, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology, Luoyang 471003, P.R. China
Received: December 13, 2019 Accepted: March 30, 2020 Published: May 13, 2020
https://doi.org/10.18632/aging.103128How to Cite
Copyright © 2020 Yan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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 α, nuclear factor κB (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-κB inhibitor / antioxidant) can also inhibit pro-inflammatory genes to a similar degree as Cytosporone B. Phosphorylated IκB-α can be inhibited by Cytosporone B, while silencing Nur77 can increase the protein expression level of phosphorylated IκB-α. After silencing IκB-α, 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 IκB-α phosphorylation expression in a Parkinson cell model. Nur77 may be a potential therapeutic target for Parkinson’s disease.