Involvement of caspases in 4-hydroxy-alkenal-induced apoptosis in human leukemic cells

W. Zhang, Q. He, L. L. Chan, F. Zhou, M. El Naghy, E. B. Thompson, N. H. Ansari

    Research output: Contribution to journalArticlepeer-review

    44 Scopus citations

    Abstract

    4-Hydroxynonenal (HNE), a reactive and cytotoxic end-product of lipid peroxidation, has been suggested to be a key mediator of oxidative stress-induced cell death and in various cell types has been shown to induce apoptosis. We have demonstrated that HNE, at micromolar concentrations, induces dose- and time-dependent apoptosis in a leukemic cell line (CEM-C7). Interestingly, much higher concentrations of HNE (>15-fold) were required to induce apoptosis in leukocytes obtained from normal individuals. We also demonstrate that HNE causes a decrease in clonogenicity of CEM-C7 cells. Furthermore, our data characterize the caspase cascade involved in HNE-induced apoptosis in CEM-C7 cells. Using specific fluorogenic substrates and irreversible peptide inhibitors, we demonstrate that caspase 2, caspase 3, and caspase 8 are involved in HNE-induced apoptosis, and that caspase 2 is the first initiator caspase that activates the executioner caspase 3, either directly or via activation of caspase 8. Our studies also suggest the involvement of another executioner caspase, which appears to be similar to caspase 8 but not caspases 2 and 3, in its specificity. The demonstration of decreased clonogenicity by HNE in the leukemic cells, and their higher susceptibility to HNE-induced apoptosis as compared to the normal cells, suggests that such compounds may have potential for leukemia chemotherapy.

    Original languageEnglish (US)
    Pages (from-to)699-706
    Number of pages8
    JournalFree Radical Biology and Medicine
    Volume30
    Issue number6
    DOIs
    StatePublished - Mar 15 2001

    Keywords

    • 4-Hydroxynonenal
    • Apoptosis
    • Caspases
    • Free radicals
    • Leukemia
    • Oxidative stress

    ASJC Scopus subject areas

    • Biochemistry
    • Physiology (medical)

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