Carbocisteine inhibits oxidant-induced apoptosis in cultured human airway epithelial cells

Motoki Yoshida, Katsutoshi Nakayama, Hiroyasu Yasuda, Hiroshi Kubo, Kazuyoshi Kuwano, Hiroyuki Arai, Mutsuo Yamaya

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

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 2O2). 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 H2O2. Treatment with L-carbocisteine reduced the proportion of apoptotic cells. In contrast, H2O 2 did not increase the concentration of LDH in supernatants of epithelial cells. Exposure to H2O2 activated caspase-3 and caspase-9, and L-carbocisteine inhibited the H2O2-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 H2O2-induced cell apoptosis. Conclusions: These findings suggest that in human airway epithelium, L-carbocisteine may inhibit cell damage induced by H2O2 through the activation of Akt phosphorylation. L-carbocisteine may have antioxidant effects, as well as mucolytic activity, in inflamed airways.

Original languageEnglish
Pages (from-to)1027-1034
Number of pages8
JournalRespirology
Volume14
Issue number7
DOIs
Publication statusPublished - 2009 Sep 1

Keywords

  • Antioxidant
  • Apoptosis
  • Chronic obstructive pulmonary disease
  • Emphysema
  • Infection and inflammation
  • Mucolytic

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine

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