APOPTOSIS IN HUMAN LUNG EPITHELIAL CELLS: TRIGGERING BY PARAQUAT AND MODULATION BY ANTIOXIDANTS

Authors

  • Graziella Cappelletti,

    Corresponding author
    1. Dipartimento di Biologia, Università degli Studi di Milano, Via Celoria 26, 20133, Milano, Italy
      Dipartimento di Biologia, Università degli Studi di Milano, Via Celoria 26, 20133, Milano, Italy
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  • Maria Grazia Maggioni,

    1. Dipartimento di Biologia, Università degli Studi di Milano, Via Celoria 26, 20133, Milano, Italy
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  • Rosalba Maci

    1. Dipartimento di Biologia, Università degli Studi di Milano, Via Celoria 26, 20133, Milano, Italy
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Dipartimento di Biologia, Università degli Studi di Milano, Via Celoria 26, 20133, Milano, Italy

Abstract

Recent results have shown that apoptosis is an important feature of the normal and injured lung epithelium, but little conclusive evidence is available about the exact intracellular mechanisms involved. In this work, we studied apoptotic cell death in the established human lung epithelial cell line, A549, by evaluating the ability of the pulmonary toxin, paraquat (1,1′-dimethyl-4,4′-bipyridylium dichloride), to act as a trigger, and assessing the ability of ascorbic acid and N-acetyl-cysteine (NAC) to modulate the process. The analysis of nuclear and cellular morphology along with TUNEL staining showed that paraquat is an inducer of apoptosis. A549 cells incubated with sublethal doses of paraquat for up to 24h showed no apoptotic features but, their following incubation in paraquat-free medium resulted in a time-dependent appearance of apoptosis. The antioxidants, ascorbic acid and NAC, proved effective in reducing paraquat-induced apoptosis, and therefore were seen as protective agents. Finally, we propose an experimental model for investigating some of the key steps in the apoptotic programme in alveolar cells.

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