Intracellular zinc depletion induces caspase activation and p21(Waf1/Cip1) cleavage in human epithelial cell lines

F. Chai, A. Q. Truong-Tran, A. Evdokiou, G. P. Young, P. D. Zalewski

    Research output: Contribution to journalShort survey

    39 Citations (Scopus)

    Abstract

    To better understand the mechanisms by which zinc deficiency induces epithelial cell death, studies were done of the effects of intracellular zinc depletion induced by the zinc chelator TPEN on apoptosis-related events in human malignant epithelial cell lines LIM1215 (colonic), NCI-H292 (bronchial), and A549 (alveolar type II). In TPEN-treated cells, depletion of zinc was followed by activation of caspase-3 (as demonstrated by enzymatic assay and Western blotting), DNA fragmentation, and morphologic changes. Increase in caspase-3 activity began 1-2 h after addition of TPEN, suggesting that zinc may suppress a step just before the activation of this caspase. Caspase-6, a mediator of caspase-3 processing, also increased, but later than caspase-3. Effects of TPEN on apoptosis were completely prevented by exogenous ZnSO4 and partially prevented by peptide caspase inhibitors. A critical substrate of caspase-3 may be the cell cycle regulator p21(Waf1/Cip1), which was rapidly cleaved in TPEN-treated cells to a 15-kDa fragment before further degradation.

    Original languageEnglish
    Pages (from-to)S85-S92
    Number of pages8
    JournalJournal of Infectious Diseases
    Volume182
    Issue number3 SUPPL. 1
    DOIs
    Publication statusPublished - Sep 2000

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