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Carbocisteine inhibits oxidant‐induced apoptosis in cultured human airway epithelial cells
Author(s) -
YOSHIDA Motoki,
NAKAYAMA Katsutoshi,
YASUDA Hiroyasu,
KUBO Hiroshi,
KUWANO Kazuyoshi,
ARAI Hiroyuki,
YAMAYA Mutsuo
Publication year - 2009
Publication title -
respirology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 85
eISSN - 1440-1843
pISSN - 1323-7799
DOI - 10.1111/j.1440-1843.2009.01594.x
Subject(s) - apoptosis , wortmannin , protein kinase b , respiratory epithelium , caspase , microbiology and biotechnology , cell culture , caspase 3 , medicine , pi3k/akt/mtor pathway , epithelium , biology , programmed cell death , biochemistry , pathology , genetics
Background and objective: Increased oxidant levels have been associated with exacerbations of COPD, and L‐carbocisteine, a mucolytic agent, reduces the frequency of exacerbations. The mechanisms underlying the inhibitory effects of L‐carbocisteine on oxidant‐induced COPD exacerbations were examined in an in vitro study of human airway epithelial cells. Methods: In order to examine the antioxidant effects of L‐carbocisteine, human tracheal epithelial cells were treated with L‐carbocisteine and exposed to hydrogen peroxide (H 2 O 2 ). Cell apoptosis was assessed using a cell death detection ELISA, and the pathways leading to cell apoptosis were examined by measurement of caspase‐3 and caspase‐9 by western blot analysis with fluorescent detection. Results: The proportion of apoptotic cells in human tracheal epithelium was increased in a concentration‐ and time‐dependent manner, following exposure to H 2 O 2 . Treatment with L‐carbocisteine reduced the proportion of apoptotic cells. In contrast, H 2 O 2 did not increase the concentration of LDH in supernatants of epithelial cells. Exposure to H 2 O 2 activated caspase‐3 and caspase‐9, and L‐carbocisteine inhibited the H 2 O 2 ‐induced activation of these caspases. L‐carbocisteine activated Akt phosphorylation, which modulates caspase activation, and the inhibitors of Akt, LY294002 and wortmannin, significantly reversed the inhibitory effects of L‐carbocisteine on H 2 O 2 ‐induced cell apoptosis. Conclusions: These findings suggest that in human airway epithelium, L‐carbocisteine may inhibit cell damage induced by H 2 O 2 through the activation of Akt phosphorylation. L‐carbocisteine may have antioxidant effects, as well as mucolytic activity, in inflamed airways.