Involvement of Bcl-2 Family in Apoptosis and Signal Pathways Induced by Cigarette Smoke Extract in the Human Airway Smooth Muscle Cells
Involvement of Bcl-2 Family in Apoptosis and Signal Pathways Induced by Cigarette Smoke Extract in the Human Airway Smooth Muscle Cells
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DOI：
10.1089/dna.2008.0782
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发表时间：
2009-01-01
影响因子：
3.1
通讯作者：
Ni, Wang
中科院分区：
文献类型：
--
作者：
Hu, Weihua;Xie, Jungang;Ni, Wang
慢性阻塞性肺疾病（COPD）是一种高度流行的气道疾病，其特征在于肺部对有害颗粒和气体的异常炎症反应。吸烟仍然是COPD发展的主要危险因素;然而，关于其对人气道平滑肌细胞（HASMCs）的影响知之甚少。本研究的目的是探讨香烟烟雾提取物（CSE）诱导HASMC凋亡的分子机制，结果表明CSE以剂量和时间依赖的方式增加HASMC活性氧（ROS）水平和细胞凋亡，而ROS清除剂N-乙酰半胱氨酸（N-acetyl-cysteine）可阻断CSE诱导HASMC的ROS水平和细胞凋亡。此外，Bax，Bad和Fas的表达增加，但Bcl-2和核因子κ B（NF-κ B B）的减少，在CSE诱导的HASMCs凋亡中呈剂量和时间依赖性。CSE可通过线粒体途径和死亡受体途径抑制HASMCs的生长并诱导其凋亡。CSE引起的氧化应激和NF-κ B B表达抑制可能在HASMCs凋亡和细胞生长抑制中起重要作用。
Chronic obstructive pulmonary disease ( COPD) is a highly prevalent airway disease characterized by an abnormal inflammatory response of the lungs to noxious particles and gases. Cigarette smoking remains a major risk factor for COPD development; however, little is known about its effect on human airway smooth muscle cells (HASMCs). The aim of this study is to examine whether apoptosis is involved in cigarette smoke extract (CSE)-induced HASMC death and the molecular mechanisms underlying it. Our studies have shown that CSE increased the level of reactive oxygen species (ROS) and cell apoptosis of HASMCs in a dose- and time-dependent manner, and the ROS scavenger N-acetyl-cysteine abrogated the effect of ROS level and apoptosis on HASMCs. Further, the expression of Bax, Bad, and Fas was increased but Bcl-2 and nuclear factor kappa B (NF-kappa B) was decreased in a dose- and time-dependent fashion in CSE-induced apoptosis in HASMCs. Taken together, CSE could inhibit the cell growth and induce apoptosis of HASMCs through both the mitochondrial pathway and death receptor pathway. Oxidative stress and inhibition of NF-kappa B expression caused by CSE may play important roles in apoptosis and inhibition of cell growth in HASMCs.