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Although the detailed molecular mechanisms are not fully understood, cellular energy status is one of the most crucial determinants for cell senescence. Creatine kinase (CK) is a constitutive enzyme, playing regulatory roles in energy homeostasis of cells. Among two isozymes, brain-type CK (CKB) is the predominant CK in lung tissue. In this study, we investigated the role of CKB in cigarette smoke extract (CSE)\u2013induced cellular senescence in human bronchial epithelial cells (HBECs). Primary HBECs and Beas2B cells were used. Protein carbonylation was evaluated as a marker of oxidative protein damage. Cellular senescence was evaluated by senescence-associated \u03b2-galactosidase staining. CKB inhibition was examined by small interfering RNA and cyclocreatine. Secretion of IL-8, a hallmark of senescence-associated secretary phenotype, was measured by ELISA. CKB expression levels were reduced in HBECs from patients with COPD compared with that of HBECs from nonsmokers. CSE induced carbonylation of CKB and subsequently decreased CKB protein levels, which was reversed by a proteasome inhibitor. CKB inhibition alone induced cell senescence, and further enhanced CSE-induced cell senescence and IL-8 secretion. CSE-induced oxidation of CKB is a trigger for proteasomal degradation. Concomitant loss of enzymatic activity regulating energy homeostasis may lead to the acceleration of bronchial epithelial cell senescence, which is implicated in the pathogenesis of COPD.<\/jats:p>","DOI":"10.1165\/rcmb.2011-0214oc","type":"journal-article","created":{"date-parts":[[2011,10,7]],"date-time":"2011-10-07T01:58:17Z","timestamp":1317952697000},"page":"306-312","source":"Crossref","is-referenced-by-count":46,"title":["Involvement of Creatine Kinase B in Cigarette Smoke\u2013Induced Bronchial Epithelial Cell Senescence"],"prefix":"10.1093","volume":"46","author":[{"given":"Hiromichi","family":"Hara","sequence":"first","affiliation":[{"name":"Division of Respiratory diseases, Department of Internal Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Araya","sequence":"additional","affiliation":[{"name":"Division of Respiratory diseases, Department of Internal 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