通过细胞外 thioredoxin 的 TRPC 通道激活.
Shang-Zhong Xu1, Piruthivi Sukumar, Fanning Zeng
1Institute of Membrane and Systems Biology, Garstang Building, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, UK.
Nature
|January 4, 2008
概括
细胞外硫素通过打破二硫化物桥梁来激活TRPC5和TRPC1离子通道. 这种新发现的机制将硫素与细胞功能联系起来,特别是在类风湿性关节炎中.
科学领域:
- 离子通道生物学 离子通道生物学
- 分子细胞生物学分子细胞生物学
- 类风湿病学 类风湿病学
背景情况:
- 哺乳动物暂时受体潜力 (TRP) 通道作为细胞传感器.
- 确定TRP通道的内源激活剂和细胞功能是一个关键的研究目标.
- 细胞外的铁素,一种氧化还原蛋白,在很大程度上是未知的细胞外点.
研究的目的:
- 研究TRPC5和TRPC1通道的激活机制.
- 确定细胞外 thioredoxin 在调节这些通道中的作用.
- 探索对类风湿性关节炎的影响.
主要方法:
- 生物化学试验,以研究由硫素激活通道.
- 对同胞细胞中TRPC5和TRPC1表达的分析.
- 功能性研究涉及道阻塞和分泌活动测量.
主要成果:
- 降低的硫素激活TRPC5同质多元和TRPC5-TRPC1异质多元通道.
- 激活通过TRPC5.5细胞外循环中的二硫化物桥梁的破坏而发生.
- TRPC5和TRPC1在类风湿性关节炎细胞中表达,并由雷多克辛激活.
- 阻断这些通道会影响细胞分泌活动.
结论:
- 已经确定了一种涉及细胞外 thioredoxin 的新型离子通道激活机制.
- 这种机制将细胞外的硫素与细胞功能联系起来,这可能与类风湿性关节炎有关.
- TRPC5-TRPC1通道代表了炎症性关节疾病的新治疗点.
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