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: Contribution to journalArticle

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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
Free Radical Scavengers
Membrane Fluidity
Membranes
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: Contribution to journalArticle

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