c-Jun降低了肺动脉光滑肌细胞中电压关闭的K(+) 通道活动
1Department of Medicine, University of California, San Diego, San Diego, CA 92103-8382, USA.
Circulation
|September 26, 2001
概括
转录因子c-Jun降低了肺动脉光滑肌细胞 (PASMCs) 中的电压通道 (K(v)) 活动. 这种K(v) 电流的减少导致了膜脱极化,的增加,并增强了PASMC的扩散.
科学领域:
- 分子生物学分子生物学
- 心血管生理学心血管生理学
- 细胞生物学 细胞生物学
背景情况:
- 电压化 (K(v)) 通道调节膜电位 (E(m),影响细胞质自由2+) 度 ([Ca(2+) ] (cyt)).
- 肺动脉光滑肌细胞 (PASMCs) 中[Ca2+][cyt]的升高促进血管收缩和增殖.
- 在此之前,c-Jun在调节PASMC中的K (v) 通道活性方面的作用尚不清楚,这是一个刺激增殖的转录因子.
研究的目的:
- 为了研究c-Jun对PASMCs中的K (v) 通道活性的影响.
- 确定c-Jun对膜潜力和PASMC扩散的影响.
主要方法:
- 使用腺病毒载体在初级培养PASMC中过度表达c-Jun.
- 使用电生理学测量K(v) 电流 (I(K(V))) 的情况.
- 单细胞RT-PCR评估了Kv1.5mRNA水平,并测量了 [3H] 提米丁结合的增殖.
主要成果:
- 在PASMCs中,c-Jun的过度表达降低了K(v) 电流和Kv1.5 mRNA水平.
- c-Jun上调Kvbeta(2) 蛋白质表达和加速I(K(V)) 失活.
- 过度表达c-Jun的PASMCs表现出膜脱极化和增加的扩散.
结论:
- c-Jun介导的PASMC扩散与减少的K (v) 通道活性有关.
- 降低K(v) 电流导致膜去极化,提高[Ca(2+) ](cyt).
- 这种机制增强了PASMC的生长,这表明c-Jun在肺高血压中发挥了作用.
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