基础医学与临床 ›› 2016, Vol. 36 ›› Issue (5): 577-580.

• 研究论文 •    下一篇

葡萄糖氧化酶诱导的氧化应激抑制α4β2烟碱型乙酰胆碱受体电流

赵君君1,郑媛1,渠静1,杨慧2,张建亮3   

  1. 1. 首都医科大学
    2. 首都医科大学北京神经科学研究所 北京神经再生与修复研究重点实验室
    3. 首都医科大学神经生物学系
  • 收稿日期:2015-07-17 修回日期:2015-12-02 出版日期:2016-05-05 发布日期:2016-04-26
  • 通讯作者: 张建亮 E-mail:jlzhang@ccmu.edu.cn
  • 基金资助:
    国家自然科学基金;国家自然科学基金;北京市教委科技计划重点项目;北京市属高等学校青年拔尖人才培育计划

The oxidative stress induced by glucose oxidase suppresses the current of α4β2 nicotinic acetylcholine receptor

  • Received:2015-07-17 Revised:2015-12-02 Online:2016-05-05 Published:2016-04-26
  • Supported by:
    National Natural Science Foundation of China;National Natural Science Foundation of China

摘要: 目的 探究葡萄糖氧化酶(GO)引起的氧化应激对α4β2烟碱型乙酰胆碱受体(nAChR)电流的影响。方法 在HEK293T细胞共转染α4和β2质粒48 h后进行实验。分为对照组(control组)、3.5 kU/L的GO处理组(GO组)、3.5 kU/L的GO与450 kU/L的过氧化氢酶(CAT)共处理组(CAT组)。使用DCFH-DA荧光探针以及激光共聚焦显微镜来检测活性氧(ROS)的产生;采用全细胞膜片钳检测α4β2 nAChR的电流变化,给予1、10 和30 μmol/L ACh检测受体功能,给予10 μmol/L ACh检测电流变化。结果 全细胞膜片钳记录到呈ACh剂量依赖性的电流;GO处理HEK293T细胞1 h后可显著地增强细胞活性氧的水平(P<0.001);对照组电流在10次给药中都保持稳定,GO组的电流在连续10次的ACh给药下逐渐降低(P<0.01);CAT组反转GO引起的α4β2 nAChR电流下降(P<0.01)。结论 GO引起的氧化应激状态导致α4β2 nAChR电流逐渐下降,α4β2 nAChR电流的下降与ROS的增多密切相关。

关键词: 活性氧, 氧化应激, 烟碱型乙酰胆碱受体

Abstract: Objective To investigate the effect of oxidative stress induced by glucose oxidase (GO) on the current of α4β2 nicotinic acetylcholine receptor (nAChR). Methods HEK293T cells were co-transfected with plasmid α4 and β2 after 48 h. Experimental groups were divided into control group, GO group and CAT group. To measure the level of reactive oxygen species (ROS), we used confocal microscopy to detect fluorescence intensity by DCFH-DA fluorescent probe; the currents of α4β2 nAChR were detected by whole-cell patch clamp. 1 μmol/L, 10 μmol/L and 30 μmol/L ACh were used to detect the receptor function. 10 μmol/L ACh was used to detect current changes. Results The currents from α4β2 nAChR in HEK293T cells were increased in a dose-dependent manner; the treatment of 3.5 kU/L GO for 1 h significantly incresed the level of ROS in HEK293T cells (P <0.001); with the consecutive application of ACh, the currents in control group were still stable after 10 times administration, while the GO-induced oxidative stress could gradually lead to the currents of α4β2 nAChR run-down (P <0.01); the 450 kU/L of catalase (CAT) could prevent the currents running down (P <0.01). Conclusion The GO-induced oxidative stress could cause α4β2 nAChR currents gradually run down. ROS may play an important role in the current run-down of α4β2 nAChR.

Key words: reactive oxygen species, oxidative stress, nicotinic acetylcholine receptor

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