Synergistic effect of cAMP and palmitate in promoting altered mitochondrial function and cell death in HepG2 cells

Linxia Zhang, Linsey C. Seitz, Amy M. Abramczyk, Christina Chan

    Research output: Research - peer-reviewArticle

    • 24 Citations

    Abstract

    Saturated free fatty acids (FFAs), e.g. palmitate, have long been shown to induce toxicity and cell death in various types of cells. In this study, we demonstrate that cAMP synergistically amplifies the effect of palmitate on the induction of cell death in human hepatocellular carcinoma cell line, HepG2 cells. Elevation of cAMP level in palmitate-treated cells led to enhanced mitochondrial fragmentation, mitochondrial reactive oxygen species (ROS) generation and mitochondrial biogenesis. Mitochondrial fragmentation precedes mitochondrial ROS generation and mitochondrial biogenesis, and may contribute to mitochondrial ROS overproduction and subsequent mitochondrial biogenesis. Fragmentation of mitochondria also facilitated the release of cytotoxic mitochondrial proteins, such as Smac, from the mitochondria and subsequent activation of caspases. However, cell death induced by palmitate and cAMP was caspase-independent and mainly necrotic.

    LanguageEnglish (US)
    Pages716-727
    Number of pages12
    JournalExperimental Cell Research
    Volume316
    Issue number5
    DOIs
    StatePublished - Mar 10 2010

    Profile

    Palmitates
    Hep G2 Cells
    Cell Death
    Organelle Biogenesis
    Reactive Oxygen Species
    Caspases
    Mitochondria
    Mitochondrial Proteins
    Nonesterified Fatty Acids
    Hepatocellular Carcinoma
    Fatty Acids
    Cell Line

    Keywords

    • Apoptosis
    • cAMP
    • Mitochondria
    • Necrosis
    • Palmitate

    ASJC Scopus subject areas

    • Cell Biology

    Cite this

    Synergistic effect of cAMP and palmitate in promoting altered mitochondrial function and cell death in HepG2 cells. / Zhang, Linxia; Seitz, Linsey C.; Abramczyk, Amy M.; Chan, Christina.

    In: Experimental Cell Research, Vol. 316, No. 5, 10.03.2010, p. 716-727.

    Research output: Research - peer-reviewArticle

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