title: The inhibitory mechanism of Cordyceps sinensis on cigarette smoke extract-induced senescence in human bronchial epithelial cells.
abstract: OBJECTIVE
  Cellular senescence is a state of irreversible growth arrest induced either by telomere shortening (replicative senescence) or stress. The bronchial epithelial cell is often injured by inhaled toxic substances, such as cigarette smoke. In the present study, we investigated whether exposure to cigarette smoke extract (CSE) induces senescence of bronchial epithelial cells; and Cordyceps sinensis mechanism of inhibition of CSE-induced cellular senescence.
  
  
  METHODS
  Human bronchial epithelial cells (16HBE cells) cultured in vitro were treated with CSE and/or C. sinensis. p16, p21, and senescence-associated-galactosidase activity were used to detect cellular senescence with immunofluorescence, quantitative polymerase chain reaction, and Western blotting. Reactive oxygen species (ROS), PI3K/AKT/mTOR and their phosphorylated proteins were examined to testify the activation of signaling pathway by ROS fluorescent staining and Western blotting. Then, inhibitors of ROS and PI3K were used to further confirm the function of this pathway.
  
  
  RESULTS
  Cellular senescence was upregulated by CSE treatment, and C. sinensis can decrease CSE-induced cellular senescence. Activation of ROS/PI3K/AKT/mTOR signaling pathway was enhanced by CSE treatment, and decreased when C. sinensis was added. Blocking ROS/PI3K/AKT/mTOR signaling pathway can attenuate CSE-induced cellular senescence.
  
  
  CONCLUSIONS
  CSE can induce cellular senescence in human bronchial epithelial cells, and ROS/PI3K/AKT/mTOR signaling pathway may play an important role in this process. C. sinensis can inhibit the CSE-induced senescence.
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China; Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People's Republic of China.
authors.forename: Ailing
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Jinxiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Pulmonary Diseases, Weihai Municipal Hospital, Weihai, Shandong, People's Republic of China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Wenxiang
authors.initials: W
authors.lastname: Bi
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Liuzhao
authors.initials: L
authors.lastname: Cao
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Yahui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pulmonary Diseases, Qilu Hospital, Shandong University, Jinan, Shandong, People's Republic of China.
authors.forename: Liang
authors.initials: L
authors.lastname: Dong
mesh_terms: D001980:Bronchi / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D032661:Cordyceps / Q000737:chemistry*; D019610:Cytoprotection; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000302:isolation & purification / Q000494:pharmacology*; D010946:Plants, Medicinal; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D012906:Smoke; C546842:MTOR protein, human; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases
keywords: COPD; Cordyceps sinensis; ROS/PI3K/AKT/mTOR signaling pathway; senescence