Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension.
Redox Regulation of Ion Channels and Receptors in Pulmonary Hypertension.
复制标题
DOI：
10.1089/ars.2018.7699
复制
发表时间：
2019-09
影响因子：
6.6
通讯作者：
Laura Weise-Cross;T. Resta;Nikki L. Jernigan
中科院分区：
文献类型：
--
作者：
Laura Weise-Cross;T. Resta;Nikki L. Jernigan
肺动脉高压（PH）的特征是由于血管收缩和正常低压肺血管重建引起的血管阻力升高。氧化还原应激通过改变膜受体、K+通道和细胞内Ca 2+稳态的调节和活性而促成这种疾病的病理生理学。最近的进展：抗氧化剂疗法在治疗PH方面的成功有限，导致人们越来越认识到，除了氧化应激之外，还原应激在肺血管细胞的代谢和细胞信号传导功能障碍中起作用。线粒体和NADPH氧化酶产生的活性氧对K+电导和膜电位以及受体操作和储存操作的Ca 2+进入有实质性影响。关键问题一些特定的氧化还原变化导致的氧化，S-亚硝基化，S-谷胱甘肽是已知的调节膜受体和离子通道的活性在PH。然而，许多网站的调节，已阐明在非肺细胞类型尚未在肺血管系统中进行测试，并缺乏上下文特异性的分子机制。未来的方向在这里，我们回顾什么是已知的膜受体和离子通道的氧化还原调节PH。进一步调查所涉及的机制，需要更好地了解PH的病因，并制定更好的有针对性的治疗策略。
SIGNIFICANCE Pulmonary hypertension (PH) is characterized by elevated vascular resistance due to vasoconstriction and remodeling of the normally low-pressure pulmonary vasculature. Redox stress contributes to the pathophysiology of this disease by altering the regulation and activity of membrane receptors, K+ channels, and intracellular Ca2+ homeostasis. Recent Advances: Antioxidant therapies have had limited success in treating PH, leading to a growing appreciation that reductive stress, in addition to oxidative stress, plays a role in metabolic and cell signaling dysfunction in pulmonary vascular cells. Reactive oxygen species generation from mitochondria and NADPH oxidases has substantial effects on K+ conductance and membrane potential, and both receptor-operated and store-operated Ca2+ entry. CRITICAL ISSUES Some specific redox changes resulting from oxidation, S-nitrosylation, and S-glutathionylation are known to modulate membrane receptor and ion channel activity in PH. However, many sites of regulation that have been elucidated in nonpulmonary cell types have not been tested in the pulmonary vasculature, and context-specific molecular mechanisms are lacking. FUTURE DIRECTIONS Here, we review what is known about redox regulation of membrane receptors and ion channels in PH. Further investigation of the mechanisms involved is needed to better understand the etiology of PH and develop better targeted treatment strategies.