A reappraisal of the role of Zn2+ in TGF-β1-induced apoptosis in primary hepatocytes

Salmaan H. Inayat-Hussain, G. M. Cohen, K. Cain

    Research output: Contribution to journalArticle

    12 Citations (Scopus)

    Abstract

    There is now a wealth of information regarding the apoptotic mode of cell death and its importance in toxicological studies in many mammalian organs including the liver. In this study, we investigated the modulatory effects of the heavy metal Zn2 + on transforming growth factor-β1 (TGF- β1-induced apoptosis in primary rat hepatocytes. Apoptosis induced by TGF- β1 (1 ng/ml) in hepatocytes was accompanied by nuclear condensation as assessed morphologically by staining with Hoechst 33258 and DNA cleavage as detected biochemically by in situ end-labeling, field inversion and conventional gel electrophoresis. Pretreatment with 100 μmol/L Zn2 + abrogated the nuclear condensation, in situ end-labeling, and DNA laddering in TGF-β1-treated hepatocytes. Surprisingly, Zn2 + did not inhibit the formation of high-molecular-weight DNA fragments (30-50 kbp to 250-300 kbp). These data provide evidence that Zn2 + exerts its effects on the endonucleases that act downstream in the execution phase of TGF-β1-induced apoptosis in hepatocytes.

    Original languageEnglish
    Pages (from-to)381-387
    Number of pages7
    JournalCell Biology and Toxicology
    Volume15
    Issue number6
    DOIs
    Publication statusPublished - 1999

    Fingerprint

    Hepatocytes
    Apoptosis
    Labeling
    Condensation
    DNA
    Bisbenzimidazole
    DNA Cleavage
    Endonucleases
    Pulsed Field Gel Electrophoresis
    Transforming Growth Factors
    Cell death
    Heavy Metals
    Electrophoresis
    Liver
    Toxicology
    Rats
    Cell Death
    Molecular Weight
    Gels
    Molecular weight

    Keywords

    • Apoptosis
    • Hepatocytes
    • In situ end-labeling
    • TGF-β
    • Zn

    ASJC Scopus subject areas

    • Cell Biology
    • Toxicology

    Cite this

    A reappraisal of the role of Zn2+ in TGF-β1-induced apoptosis in primary hepatocytes. / Inayat-Hussain, Salmaan H.; Cohen, G. M.; Cain, K.

    In: Cell Biology and Toxicology, Vol. 15, No. 6, 1999, p. 381-387.

    Research output: Contribution to journalArticle

    Inayat-Hussain, Salmaan H. ; Cohen, G. M. ; Cain, K. / A reappraisal of the role of Zn2+ in TGF-β1-induced apoptosis in primary hepatocytes. In: Cell Biology and Toxicology. 1999 ; Vol. 15, No. 6. pp. 381-387.
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