Disruption of the Circadian Clock Alters Antioxidative Defense via the SIRT1-BMAL1 Pathway in 6-OHDA-Induced Models of Parkinson's Disease.
Disruption of the Circadian Clock Alters Antioxidative Defense via the SIRT1-BMAL1 Pathway in 6-OHDA-Induced Models of Parkinson's Disease.
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在 6-OHDA 诱导的帕金森病模型中，昼夜节律时钟的破坏通过 SIRT1-BMAL1 途径改变抗氧化防御
DOI：
10.1155/2018/4854732
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发表时间：
2018
影响因子：
--
通讯作者：
Liu CF
中科院分区：
文献类型：
--
作者：
Wang Y;Lv D;Liu W;Li S;Chen J;Shen Y;Wang F;Hu LF;Liu CF
帕金森病（PD）是第二常见的神经退行性疾病，并且已知涉及昼夜节律功能障碍和氧化应激。尽管抗氧化防御受分子生物钟的调节，但很少有研究探讨它们在PD中的功能以及沉默信息调节因子1（SIRT 1）对它们的调节。我们推测PD模型中抗氧化活性的降低是通过SIRT 1通路导致分子生物钟功能障碍。我们用6-羟基多巴胺（6-OHDA）处理大鼠和SH-SY 5 Y细胞，并使用实时定量PCR测量核心昼夜节律钟和相关核受体基因的表达，以及SIRT 1，脑和肌肉Arnt样蛋白1（BMAL 1）和乙酰化BMAL 1的水平。我们发现，6-OHDA治疗改变了体内和体外的时钟和抗氧化分子的表达模式。我们还检测到乙酰化BMAL 1：BMAL 1的比例增加和SIRT 1水平降低。此外，白藜芦醇，SIRT 1的激活剂，减少BMAL 1的乙酰化，并抑制其与BMAL 1的结合，从而逆转由6-OHDA诱导的受损的抗氧化活性。这些结果表明，功能失调的生物钟有助于通过SIRT 1依赖性BMAL 1途径在PD中的异常抗氧化反应。
Parkinson's disease (PD) is the second most common neurodegenerative disease and is known to involve circadian dysfunction and oxidative stress. Although antioxidative defense is regulated by the molecular circadian clock, few studies have examined their function in PD and their regulation by silent information regulator 1 (SIRT1). We hypothesize that reduced antioxidative activity in models of PD results from dysfunction of the molecular circadian clock via the SIRT1 pathway. We treated rats and SH-SY5Y cells with 6-hydroxydopamine (6-OHDA) and measured the expression of core circadian clock and associated nuclear receptor genes using real-time quantitative PCR as well as levels of SIRT1, brain and muscle Arnt-like protein 1 (BMAL1), and acetylated BMAL1 using Western blotting. We found that 6-OHDA treatment altered the expression patterns of clock and antioxidative molecules in vivo and in vitro. We also detected an increased ratio of acetylated BMAL1:BMAL1 and a decreased level of SIRT1. Furthermore, resveratrol, an activator of SIRT1, decreased the acetylation of BMAL1 and inhibited its binding with CRY1, thereby reversing the impaired antioxidative activity induced by 6-OHDA. These results suggest that a dysfunctional circadian clock contributes to an abnormal antioxidative response in PD via a SIRT1-dependent BMAL1 pathway.
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影响因子：
5.1
作者：
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通讯作者：
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