Hydrogen sulfide inhibits MPP(+)-induced apoptosis in PC12 cells.
Hydrogen sulfide inhibits MPP(+)-induced apoptosis in PC12 cells.
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DOI：
10.1016/j.lfs.2009.05.023
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发表时间：
2009-08
期刊：
影响因子：
6.1
通讯作者：
Wei-lan Yin;Jianqin He;Bi Hu;Zhi-Sheng Jiang;Xiao-Qing Tang
中科院分区：
文献类型：
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作者：
Wei-lan Yin;Jianqin He;Bi Hu;Zhi-Sheng Jiang;Xiao-Qing Tang
硫化氢（H2S）是一种众所周知的细胞毒性气体。最近，它已被证明可以保护神经元免受谷氨酸、次氯酸（HOCl）和β -淀粉样蛋白引起的氧化应激。本研究的目的是探讨H2S对1-甲基-4-苯基吡啶离子（MPP+）诱导的大鼠嗜铬细胞瘤细胞系PC12细胞凋亡的保护作用及其分子机制。主要方法采用常规的3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑还原法测定细胞活力。碘化丙啶染色后采用Hoechst 33258核染色和流式细胞术（FCM）检测细胞凋亡。用罗丹明123 （Rh123）探针测定线粒体膜电位（MMP），用FCM法用二氢霍达明探针测定活性氧（ROS）。smpp +降低细胞活力，诱导PC12细胞凋亡，同时MMP的耗散和ROS的过量产生。氢硫化钠（NaHS）， H2S供体，保护PC12细胞免受MPP+诱导的细胞毒性和凋亡，不仅通过减少MMP的损失，而且通过减弱细胞内ROS的增加。H2S对MPP+诱导的PC12细胞毒性和凋亡具有明显的保护作用，这与H2S抑制MPP+诱导的MMP耗散和ROS过量产生有关。这些发现可以显著推进与氧化应激相关的神经退行性疾病的治疗方法，如帕金森病。
AIMSHydrogen sulfide (H2S) is a well-known cytotoxic gas. Recently it has been shown to protect neurons against oxidative stress caused by glutamate, hypochlorous acid (HOCl), and beta-amyloid. The aim of the present study is to explore the cytoprotection of H2S against 1-methyl-4-phenylpyridinium ion (MPP+)-induced apoptosis and the molecular mechanisms underlying in PC12 cells, a rat cell line derived from pheochromocytoma cells.MAIN METHODSCell viability was determined by the conventional 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assay. Apoptosis was assessed by Hoechst 33258 nuclear staining and flow cytometric (FCM) analysis after propidium iodide staining. The mitochondrial membrane potential (MMP) was measured by rhodamine 123 (Rh123) probe and reactive oxygen species (ROS) were measured by dihydrorhodamine probe using FCM analysis.KEY FINDINGSMPP+reduced the cell viability and induced apoptosis of PC12 cells along with dissipation of MMP as well as overproduction of ROS. Sodium hydrosulfide (NaHS), a H2S donor, protected PC12 cells against MPP+-induced cytotoxicity and apoptosis not only by reducing the loss of MMP, but also by attenuating an increase in intracellular ROS.SIGNIFICANCEH2S significantly protected PC12 cells against cytotoxicity and apoptosis induced by MPP+, which was associated with the inhibition by H2S of MPP+-induced dissipation of MMP and overproduction of ROS. These findings can significantly advance therapeutic approaches to the neurodegenerative diseases which are associated with oxidative stress, such as Parkinson's disease.