Cruciferous nutraceutical 3H-1,2-dithiole-3-thione protects human primary astrocytes against neurocytotoxicity elicited by MPTP, MPP(+), 6-OHDA, HNE and acrolein.
Cruciferous nutraceutical 3H-1,2-dithiole-3-thione protects human primary astrocytes against neurocytotoxicity elicited by MPTP, MPP(+), 6-OHDA, HNE and acrolein.
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十字花科营养保健品 3H-1,2-二硫醇-3-硫酮可保护人原代星形胶质细胞免受 MPTP、MPP( )、6-OHDA、HNE 和丙烯醛引起的神经细胞毒性。
DOI：
10.1007/s11064-009-9978-8
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发表时间：
2009
影响因子：
4.4
通讯作者：
Misra,HaraP
中科院分区：
文献类型：
--
作者：
Jia,Zhenquan;Zhu,Hong;Li,Yunbo;Misra,HaraP
星形胶质细胞在维持正常脑功能和为神经元提供营养支持方面发挥着重要作用。它们还遭受一系列毒性损害，是促氧化剂的主要目标，例如 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)、1-甲基-4-苯基吡啶鎓 (MPP+)、6-羟基多巴胺 (6-OHDA)、4-羟基-2-壬烯醛 (HNE) 和丙烯醛。最近，我们观察到细胞抗氧化剂和 2 相酶可以被 3H-1,2-二硫醇-3-硫酮 (D3T)（十字花科蔬菜中的一种营养保健品）上调，对抗人神经母细胞瘤细胞系 (SH-SY5Y) 中的许多促氧化剂。然而，星形胶质细胞中D3T对上述细胞因子的调节及其在改善上述神经毒素的神经毒性作用中的作用尚未被研究。在这项研究中，我们发现，将人原代星形胶质细胞与微摩尔浓度 (5–100 μM) 的 D3T 孵育 24 小时，会导致还原型谷胱甘肽 (GSH)、谷胱甘肽还原酶 (GR) 和 2 相酶 NAD(P)H:醌氧化还原酶 1 (NQO1) 的水平显着增加。 D3T 处理还引起这些细胞中 γ-谷氨酰半胱氨酸连接酶催化亚基 (GCLC)、GR 和 NQO1 mRNA 表达的时间依赖性增加。研究发现，用 D3T 预处理星形胶质细胞可显着防止 MPTP、MPP+、6-OHDA、HNE 和丙烯醛引起的神经细胞毒性。总而言之，这项研究首次证明，在人类星形胶质细胞中，十字花科营养保健品 D3T 有效诱导细胞 GSH 系统和 2 相酶 NQO1，同时这些细胞对各种神经毒物引起的损伤的抵抗力显着增强。这项研究的结果可能对新型神经保护策略的开发具有重要意义。
Astrocytes possess important roles in maintaining normal brain function and providing trophic support to the neurons. They also suffer a range of toxic insults, being a chief target of prooxidants such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), 1-methyl-4-phenylpyridinium (MPP+), 6-hydroxydopamine (6-OHDA), 4-hydroxy-2-nonenal (HNE), and acrolein. Recently, we have observed that the cellular antioxidants and phase 2 enzymes can be upregulated by 3H-1,2-dithiole-3-thione (D3T), a nutraceutical found in cruciferous vegetables, against many prooxidants in human neuroblastoma cell lines (SH-SY5Y). However, the regulation of the above cellular factors by D3T in astrocytes and their role in ameliorating the neurotoxic effects of the above neurotoxins have not been investigated. In this study, we show that incubation of human primary astrocytes with micromolar concentrations (5–100 μM) of D3T for 24 h resulted in significant increases in the levels of reduced glutathione (GSH), glutathione reductase (GR), and the phase 2 enzyme NAD(P)H:quinone oxidoreductase 1 (NQO1). D3T treatment also caused time-dependent increases in mRNA expression of the gamma-glutamylcysteine ligase catalytic subunit (GCLC), GR, and of NQO1 in these cells. Pretreatment of astrocytes with D3T was found to afford remarkable protection against the neurocytotoxicity elicited by MPTP, MPP+, 6-OHDA, HNE and acrolein. Taken together, this study demonstrates for the first time that in human astrocytes, the cruciferous nutraceutical D3T potently induces the cellular GSH system and the phase 2 enzyme NQO1, which is accompanied by dramatically increased resistance of these cells to the damage induced by various neurotoxicants. The results of this study may have important implications for the development of novel neuroprotective strategies.