title: Bronchiolar epithelial catalase is diminished in smokers with mild COPD.
abstract: This study aimed to investigate bronchiolar catalase expression and its relationship with smoking and/or chronic obstructive pulmonary disease (COPD) in humans and to determine the dynamic change of bronchiolar catalase expression in response to cigarette smoke in mice. Lung tissue was obtained from 36 subjects undergoing surgery for peripheral tumours, consisting of life-long nonsmokers and smokers with or without COPD. Male C57BL/6 mice were subjected to cigarette smoke exposure for up to 3 months followed by a 28-day cessation period. We quantified bronchiolar catalase mRNA using laser capture microdissection and quantitative reverse transcription-polymerase chain reaction. C22 club cells (Clara cells) in culture were exposed to cigarette smoke extract and monitored for viability when catalase expression was decreased by siRNA. Catalase was decreased at mRNA and protein levels in bronchiolar epithelium in smokers with COPD. In mice, bronchiolar catalase is temporarily upregulated at 1 day after cigarette smoke exposure but is downregulated by repeated cigarette smoke exposure, and is not restored long after withdrawal once emphysema is developed. Decreasing catalase expression in C22 cells resulted in greater cigarette smoke extract-induced cell death. Bronchiolar catalase reduction is associated with COPD. Regulation of catalase depends on the duration of cigarette smoke exposure, and plays a critical role for protection against cigarette smoke-induced cell damage.
authors.affiliation: Division of Pulmonary Medicine, Dept of Medicine, Keio University School of Medicine, Tokyo, Japan. tbetsuyaku@z5.keio.jp
authors.forename: Tomoko
authors.initials: T
authors.lastname: Betsuyaku
authors.forename: Satoshi
authors.initials: S
authors.lastname: Fuke
authors.forename: Takashi
authors.initials: T
authors.lastname: Inomata
authors.forename: Kichizo
authors.initials: K
authors.lastname: Kaga
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Morikawa
authors.forename: Nao
authors.initials: N
authors.lastname: Odajima
authors.forename: Tracy
authors.initials: T
authors.lastname: Adair-Kirk
authors.forename: Masaharu
authors.initials: M
authors.lastname: Nishimura
mesh_terms: D000368:Aged; D000818:Animals; D001980:Bronchi / Q000201:enzymology*; D002374:Catalase / Q000378:metabolism*; D004195:Disease Models, Animal; D004848:Epithelium / Q000201:enzymology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008168:Lung / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology* / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D012333:RNA, Messenger; C577219:CAT protein, human; D002374:Catalase