Intrinsic pathway of hydroquinone induced apoptosis occurs via both caspase-dependent and caspase-independent mechanisms

Salmaan H. Inayat-Hussain, David Ross

    Research output: Contribution to journalArticle

    24 Citations (Scopus)

    Abstract

    The role of mitochondria and apical caspases in apoptosis induced by the benzene metabolite hydroquinone (HQ) remains to be elucidated. Here, we investigated the involvement of mitochondria and activation of the apical caspases-8 and -9 in HQ induced apoptosis in myeloperoxidase (MPO)-rich HL-60 and MPO-deficient Jurkat T cells. Treatment of HL-60 and Jurkat cells with HQ resulted in apoptosis as assessed by phosphatidyl serine (PS) exposure, loss of mitochondrial transmembrane potential (MTP), release of cytochrome c, and processing of apical caspases-8 and -9 and executioner caspase-3. In HQ-treated HL-60 cells, pretreatment with the pan-caspase inhibitor benzyloxycarbonyl-Val- Ala-Asp-fluoromethyl ketone (ZVAD), which did not inhibit PS exposure, also failed to abrogate the loss of MTP and release of cytochrome c. However, complete processing of caspase-9 was inhibited in the presence of ZVAD. In marked contrast, in HQ-treated Jurkat cells, ZVAD significantly abrogated PS exposure, loss of MTP, and caspase-9 processing but not release of cytochrome c. Although ZVAD-sensitive caspase-8 processing occurred in both cell types, pretreatment with either fas-receptor blocking ZB4 or fas-ligand NOK1 neutralizing antibodies did not inhibit HQ-induced apoptosis. In conclusion, our results demonstrate that HQ induced apoptosis in Jurkat cells occurs via a ZVAD-inhibitable, caspase-dependent process, while in HL-60 cells, apoptosis occurs predominantly via caspase-independent mechanisms. Our results emphasize that both caspase-dependent and independent mechanisms should be considered in the intrinsic apoptotic pathway induced by HQ.

    Original languageEnglish
    Pages (from-to)420-427
    Number of pages8
    JournalChemical Research in Toxicology
    Volume18
    Issue number3
    DOIs
    Publication statusPublished - 1 Mar 2005

    Fingerprint

    Caspases
    Apoptosis
    Jurkat Cells
    Caspase 9
    Caspase 8
    HL-60 Cells
    Phosphatidylserines
    Cytochromes c
    Membrane Potentials
    Mitochondria
    Processing
    Peroxidase
    CD95 Antigens
    Fas Ligand Protein
    Caspase Inhibitors
    T-cells
    hydroquinone
    Metabolites
    Benzene
    Neutralizing Antibodies

    ASJC Scopus subject areas

    • Drug Discovery
    • Organic Chemistry
    • Chemistry(all)
    • Toxicology
    • Health, Toxicology and Mutagenesis

    Cite this

    Intrinsic pathway of hydroquinone induced apoptosis occurs via both caspase-dependent and caspase-independent mechanisms. / Inayat-Hussain, Salmaan H.; Ross, David.

    In: Chemical Research in Toxicology, Vol. 18, No. 3, 01.03.2005, p. 420-427.

    Research output: Contribution to journalArticle

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