高等学校化学学报 ›› 2015, Vol. 36 ›› Issue (11): 2322.doi: 10.7503/cjcu20150723

• 有机化学 • 上一篇    下一篇

一种新型化合物的合成及对PC12高分化细胞的神经保护作用

胡爽1, 滕利荣1, 张峻榕1, 孟珈同1, 庄哲2, 杜梦妍1, 王迪1(), 寮渭巍2()   

  1. 1. 吉林大学生命科学学院, 长春 130012
    2. 化学学院有机化学系, 长春 130012
  • 出版日期:2015-11-10 发布日期:2015-10-21
  • 作者简介:联系人简介: 王 迪, 男, 博士, 讲师, 主要从事生物天然大分子及化学合成小分子药理毒理方面的研究. E-mail:jluwangdi@outlook.com;寮渭巍, 男, 博士, 教授, 主要从事有机合成方面的研究. E-mail:wliao@jlu.edu.cn
  • 基金资助:
    国家自然科学基金(批准号: 81402955)资助

Synthesis of a Novel Compound and Mediated Neuro-protection in Differentiated PC12 Cells via Mitochondria Related Pathway

HU Shuang1, TENG Lirong1, ZHANG Junrong1, MENG Jiatong1, ZHUANG Zhe2, DU Mengyan1, WANG Di1,*(), LIAO Weiwei2,*()   

  1. 1. School of Life Sciences, College of Chemistry,Jilin University, Changchun 130012, China
    2. Department of Organic Chemistry, College of Chemistry,Jilin University, Changchun 130012, China
  • Online:2015-11-10 Published:2015-10-21
  • Contact: WANG Di,LIAO Weiwei E-mail:jluwangdi@outlook.com;wliao@jlu.edu.cn

摘要:

研究了一种新合成化合物(3h8b)的神经保护作用及初步分子机制. 该化合物具有缓解神经毒素6-羟基多巴胺(6-OHDA)和L-谷氨酸(L-Glu)诱导高分化PC12细胞损伤的作用. 可有效改善神经毒素对高分化PC12细胞的损伤, 明显增强细胞活力, 降低细胞核凋亡比率, 抑制细胞内钙离子过载. 经3h8b处理之后, 神经毒素引起的细胞内线粒体膜电位异常显著恢复. 进一步的实验表明, 3h8b可以逆转神经毒素造成的Bcl-2和Bcl-xL抑制性表达. 实验证实3h8b通过线粒体相关途经对高分化PC12细胞起保护作用, 为通过化学合成法获得具有治疗神经退行性病变作用的新型化合物提供了理论依据.

关键词: 神经保护, 6-羟基多巴胺, L-谷氨酸, 线粒体

Abstract:

The neuro-protective effect of a new synthetic compound named 3h8b on differentiated PC12(DPC12) cells against neurotoxins 6-hydroxydopamine(6-OHDA)- and L-glutamic acid(L-Glu)-induced cell injury and potential mechanisms were investigated. Data show that 3h8b significantly enhanced cell viability, improved nucleus morphological apoptotic alterations, and relieved intracellular Ca2+ overload caused by neurotoxins in DPC12 cells. The abnormal alteration of mitochondria in neurotoxins-treated cells was strongly restored by 3h8b. Further experiments demonstrate that 3h8b reverses neurotoxins-suppressed levels of B-cell lymphoma 2(Bcl-2) and Bcl-xL. All these results indicate that mitochondria related pathway is essential for the neuro-protective effect of the novel synthetic compound 3h8b against neurotoxins-induce toxicity in DPC12 cells.

Key words: Neuroprotection, 6-Hydroxydopamine, L-glutamate, Mitochondria

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