PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons.

PKCδ mediates paraquat-induced Nox1 expression in dopaminergic neurons.
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PKCδ介导了多巴胺能神经元中帕拉奎特诱导的NOX1表达。

DOI:
10.1016/j.bbrc.2013.06.085
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发表时间:
2013-08-02
影响因子:
3.1
通讯作者:
Kim, Yoon-Seong
Kim, Yoon-Seong
中科院分区:
生物学4区
文献类型:
--
作者:
Cristovao, Ana Clara;Barata, Joana;Je, Goun;Kim, Yoon-Seong

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我们之前的工作表明,(NADPH) 氧化酶 (Nox),特别是 Nox1,在百草枯 (PQ) 引起的氧化应激和随后的多巴胺能细胞死亡中发挥重要作用。在非神经元和神经胶质细胞中,蛋白激酶 C δ (PKCδ) 显示出调节 Nox 系统活性的能力。在此,我们的目的是研究在暴露于 PQ 的多巴胺能神经元中,PKCδ 是否也可以调节 Nox1 表达。化学抑制剂 Rottlerin 和短干扰 RNA (siRNA) 分别用于抑制或选择性敲低 PKCδ。这些研究是使用暴露于 PQ 的永生化大鼠中脑多巴胺能细胞系(N27 细胞)进行的,在与 Rottlerin 预孵育或用 PKCδ-siRNA 转染后。我们观察到抑制或敲除 PKCδ 显着降低 PQ 诱导的 Nox1 转录物和蛋白水平、ROS 生成以及随后的多巴胺能细胞死亡。结果表明,PKCδ 在 PQ 引发的 Nox1 介导的氧化应激的调节中发挥作用,并可能在帕金森病的发病机制中发挥作用。
Our previous works have shown that the (NADPH) oxidase (Nox) enzyme, in particular Nox1, plays an important role in oxidative stress and subsequent dopaminergic cell death elicited by paraquat (PQ). In non-neuronal and glial cells, protein kinase C δ (PKCδ) shows the ability to regulate the activity of the Nox system. Herein we aimed to investigate if also in dopaminergic neurons exposed to PQ, PKCδ can regulate Nox1expression. The chemical inhibitor, rottlerin, and short interference RNA (siRNA) were used to inhibit or selectively knockdown PKCδ, respectively. The studies were performed using the immortalized rat mesencephalic dopaminergic cell line (N27 cells) exposed to PQ, after pre-incubation with rottlerin or transfected with PKCδ-siRNA. We observed that inhibition or knockdown of PKCδ significantly reduced PQ induced Nox1 transcript and protein levels, ROS generation and subsequent dopaminergic cell death. The results suggest that PKCδ plays a role in the regulation of Nox1-mediated oxidative stress elicited by PQ and could have a role in the pathogenesis of Parkinson’s disease.
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