Pretreatment of Ascorbic Acid Inhibits MPTP-Induced Astrocytic Oxidative Stress through Suppressing NF-κB Signaling.
Pretreatment of Ascorbic Acid Inhibits MPTP-Induced Astrocytic Oxidative Stress through Suppressing NF-κB Signaling.
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抗坏血酸预处理通过抑制 NF-κ B 信号传导抑制 MPTP 诱导的星形胶质细胞氧化应激
DOI：
10.1155/2020/8872296
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发表时间：
2020
影响因子：
3.1
通讯作者：
Qu S
中科院分区：
文献类型：
--
作者：
Zeng X;Xu K;Wang J;Xu Y;Qu S
星形胶质细胞是中枢神经系统（CNS）的主要组成部分。星形胶质细胞氧化应激有助于帕金森病（PD）的发展。维持星形胶质细胞中活性氧和活性氮（ROS/RNS）的抗氧化和解毒作用对预防PD至关重要。研究表明，抗坏血酸刺激人神经母细胞瘤细胞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和调控机制尚不清楚。我们的研究目的是深入研究AA对星形胶质细胞解毒的调控机制。我们发现AA预处理降低了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。相反，在MPP+处理的星形胶质细胞中，AA预处理后抗氧化物质（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物（GCLM）亚基）的表达水平上调。然而，MPP+处理后，抑制NF-κB可阻止AA诱导的星形胶质细胞抗氧化物质的增加，提示AA通过抑制NF-κB介导的氧化应激来改善星形胶质细胞的抗氧化功能。此外，体内研究表明，AA预给药还能抑制mptp处理小鼠中脑NF-κB和上调抗氧化物质的表达水平。此外，AA预处理可减轻mptp诱导的小鼠pd样病理。综上所述，我们的研究结果表明，预给药AA可通过抑制NF-κB信号传导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。因此，我们的研究结果阐明了AA对星形胶质细胞的一种新的保护机制。
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-κB prevented such AA induced increases in antioxidative substances following MPP+ treatment in astrocytes, suggesting that AA improved antioxidative function of astrocytes through inhibiting NF-κB-mediated oxidative stress. Furthermore, in vivo studies revealed that AA preadministration also suppressed NF-κB 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-κB signaling, following alleviated the pathogenesis of PD which induced by MPTP. Hence, our findings elucidate a novel protective mechanism of AA in astrocytes.
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作者：
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通讯作者：
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