Experimental and computational studies investigating trehalose protection of HepG2 cells from palmitate-induced toxicity

Sukit Leekumjorn, Yifei Wu, Amadeu K. Sum, Christina Chan

    Research output: Research - peer-reviewArticle

    • 25 Citations

    Abstract

    Understanding the mechanism of saturated fatty acid-induced hepatocyte toxicity may provide insight into cures for diseases such as obesity-associated cirrhosis. Trehalose, a nonreducing disaccharide shown to protect proteins and cellular membranes from inactivation or denaturation caused by different stress conditions, also protects hepatocytes from palmitateinduced toxicity. Our results suggest that trehalose serves as a free radical scavenger and alleviates damage from hydrogen peroxide secreted by the compromised cells. We also observe that trehalose protects HepG2 cells by interacting with the plasma membrane to counteract the changes in membrane fluidity induced by palmitate. The experimental results are supported by molecular dynamics simulations of model cell membranes that closely reflect the experimental conditions. Simulations were performed to understand the specific interactions between lipid bilayers, palmitate, and trehalose. The simulations results reveal the early stages of how palmitate induces biophysical changes to the cellular membrane and the role of trehalose in protecting the membrane structure.

    LanguageEnglish (US)
    Pages2869-2883
    Number of pages15
    JournalBiophysical Journal
    Volume94
    Issue number7
    DOIs
    StatePublished - Apr 2008

    Profile

    Trehalose
    Palmitates
    Hep G2 Cells
    Hepatocytes
    Cell Membrane
    Membranes
    Free Radical Scavengers
    Membrane Fluidity
    Disaccharides
    Lipid Bilayers
    Molecular Dynamics Simulation
    Hydrogen Peroxide
    Membrane Proteins
    Fibrosis
    Fatty Acids
    Obesity

    ASJC Scopus subject areas

    • Biophysics

    Cite this

    Experimental and computational studies investigating trehalose protection of HepG2 cells from palmitate-induced toxicity. / Leekumjorn, Sukit; Wu, Yifei; Sum, Amadeu K.; Chan, Christina.

    In: Biophysical Journal, Vol. 94, No. 7, 04.2008, p. 2869-2883.

    Research output: Research - peer-reviewArticle

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