Central Laboratory, Shunde Hospital, Southern Medical University (The First People's Hospital of Shunde Foshan), Foshan, 528300 Guangdong, China.
Department of Neurology, Nanfang Hospital, Southern Medical University/The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong 510515, China.
Neural Plast. 2020 Nov 17;2020:8872296. doi: 10.1155/2020/8872296. eCollection 2020.
Astrocytes are a major constituent of the central nervous system (CNS). Astrocytic oxidative stress contributes to the development of Parkinson's disease (PD). Maintaining production of antioxidant and detoxification of reactive oxygen and nitrogen species (ROS/RNS) in astrocytes is critical to prevent PD. Study has illuminated that ascorbic acid (AA) stimulates dopamine synthesis and expression of tyrosine hydroxylase in human neuroblastoma cells. However, the role and regulatory mechanisms of AA on detoxification of astrocytes are still unclear. The purpose of our study is in-depth study of the regulatory mechanism of AA on detoxification of astrocytes. We found that AA pretreatment decreased the expression of ROS and inducible nitric oxide synthase (iNOS) in MPP-treated astrocytes. In contrast, the expression levels of antioxidative substances-including superoxide dismutase (SOD), glutathione (GSH), and glutamate-cysteine ligase modifier (GCLM) subunit-were upregulated after AA pretreatment in MPP-treated astrocytes. However, inhibition of NF-B prevented such AA induced increases in antioxidative substances following MPP treatment in astrocytes, suggesting that AA improved antioxidative function of astrocytes through inhibiting NF-B-mediated oxidative stress. Furthermore, studies revealed that AA preadministration also suppressed NF-B and upregulated the expression levels of antioxidative substances in the midbrain of MPTP-treated mice. Additionally, pretreatment of AA alleviated MPTP-induced PD-like pathology in mice. Taken together, our results demonstrate that preadministration of AA improves the antioxidative function of astrocytes through suppressing NF-B signaling, following alleviated the pathogenesis of PD which induced by MPTP. Hence, our findings elucidate a novel protective mechanism of AA in astrocytes.
星形胶质细胞是中枢神经系统 (CNS) 的主要组成部分。星形胶质细胞的氧化应激有助于帕金森病 (PD) 的发展。维持星形胶质细胞中抗氧化剂的产生和活性氧和氮物种 (ROS/RNS) 的解毒对于预防 PD 至关重要。研究表明，抗坏血酸 (AA) 可刺激人神经母细胞瘤细胞中多巴胺的合成和酪氨酸羟化酶的表达。然而，AA 对星形胶质细胞解毒的作用及其调节机制尚不清楚。我们的研究目的是深入研究 AA 对星形胶质细胞解毒的调节机制。我们发现 AA 预处理可降低 MPP 处理的星形胶质细胞中 ROS 和诱导型一氧化氮合酶 (iNOS) 的表达。相比之下，AA 预处理可上调 MPP 处理的星形胶质细胞中抗氧化物质的表达水平，包括超氧化物歧化酶 (SOD)、谷胱甘肽 (GSH) 和谷氨酸半胱氨酸连接酶修饰亚基 (GCLM)。然而，NF-B 的抑制可防止 AA 诱导的 MPP 处理后星形胶质细胞中抗氧化物质的增加，表明 AA 通过抑制 NF-B 介导的氧化应激来改善星形胶质细胞的抗氧化功能。此外，研究表明 AA 预处理还可抑制 MPTP 处理的小鼠中 NF-B 的表达并上调抗氧化物质的表达水平。此外，AA 的预处理可减轻 MPTP 诱导的 PD 样病理。总之，我们的研究结果表明，AA 通过抑制 NF-B 信号通路，改善星形胶质细胞的抗氧化功能，从而减轻 MPTP 诱导的 PD 发病机制，从而阐明了 AA 在星形胶质细胞中的一种新的保护机制。
