Involvement of Bcl-2 family in apoptosis and signal pathways induced by cigarette smoke extract in the human airway smooth muscle cells.
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-kappaB (NF-kappaB) 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-kappaB expression caused by CSE may play important roles in apoptosis and inhibition of cell growth in HASMCs.
Hu
Weihua
W
Department of Respiratory Medicine, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Xie
Jungang
J
Zhao
Jianping
J
Xu
Yongjian
Y
Yang
Shifang
S
Ni
Wang
W
D000111:Acetylcysteine / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053222:Fas Ligand Protein / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008168:Lung / Q000166:cytology*; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D012906:Smoke / Q000009:adverse effects*; D013859:Thiocarbamates / Q000494:pharmacology; D014026:Nicotiana / Q000737:chemistry*; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; C494819:BAD protein, human; C494826:BAX protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; D011759:Pyrrolidines; C498143:RELA protein, human; D017382:Reactive Oxygen Species; D012906:Smoke; D013859:Thiocarbamates; D051996:Transcription Factor RelA; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D019014:fas Receptor; C020972:pyrrolidine dithiocarbamic acid; D000111:Acetylcysteine