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3α-乙酰氧基-桉叶-1,4(15),11(13)-三烯-12,6α-内酯对多巴胺诱导的人神经母细胞瘤 SH-SY5Y 细胞凋亡的神经保护作用。

Neuroprotective effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide against dopamine-induced apoptosis in the human neuroblastoma SH-SY5Y cell line.

机构信息

Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul 151-742, Republic of Korea.

出版信息

Neurochem Res. 2011 Nov;36(11):1991-2001. doi: 10.1007/s11064-011-0523-1. Epub 2011 Jun 18.

Abstract

Dopamine (DA), as a neurotoxin, can elicit severe Parkinson's disease-like syndrome by elevating intracellular reactive oxygen species (ROS) levels and apoptotic activity. We examined the inhibitory effects of 3α-acetoxyeudesma-1,4(15),11(13)-trien-12,6α-olide (AETO), purified from the leaves of Laurus nobilis L., on DA-induced apoptosis and α-synuclein (α-syn) formation in dopaminergic SH-SY5Y cells. AETO decreased the active form of caspase-3 and the levels of p53, which were accompanied by increased levels of Bcl-2 in a dose-dependent manner. Flow cytometric and Western blot analysis showed that AETO significantly inhibited DA-induced apoptosis along with suppression of intracellular tyrosinase activity, ROS generation, quinoprotein, and α-syn formation (P < 0.01). These results indicate that AETO inhibited DA-induced apoptosis, which is closely related to the suppression of intracellular tyrosinase activity and the formation of α-syn, ROS, and quinoprotein in SH-SY5Y cells.

摘要

多巴胺(DA)作为一种神经毒素,可通过提高细胞内活性氧(ROS)水平和促凋亡活性引发严重的帕金森病样综合征。我们研究了从月桂叶中分离出的 3α-乙酰氧基桉叶-1,4(15),11(13)-三烯-12,6α-内酯(AETO)对多巴胺诱导的凋亡和α-突触核蛋白(α-syn)形成在多巴胺能 SH-SY5Y 细胞中的抑制作用。AETO 呈剂量依赖性降低 caspase-3 的活性形式和 p53 的水平,同时增加 Bcl-2 的水平。流式细胞术和 Western blot 分析表明,AETO 可显著抑制多巴胺诱导的细胞凋亡,同时抑制细胞内酪氨酸酶活性、ROS 生成、醌蛋白和 α-syn 形成(P<0.01)。这些结果表明,AETO 抑制多巴胺诱导的凋亡与抑制细胞内酪氨酸酶活性以及 SH-SY5Y 细胞中 α-syn、ROS 和醌蛋白的形成密切相关。

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