Experimental and Computational Studies Investigating Trehalose Protection of HepG2 Cells from Palmitate Induced Toxicity
Sukit Leekumjorn 1, Yifei Wu 2, Amadeu K Sum 1 and Christina Chan 2*
1 Virginia Polytechnic Institute & State University
2 Michigan State University
* To whom correspondence should be addressed. E-mail: krischan{at}egr.msu.edu.
Submitted on August 28, 2007
Revised on September 21, 2007
Accepted on 20 November 2007
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Abstract |
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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 palmitate induced 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.
Key Words:
HepG2 cells, experiments, membrane fluidity, palmitate, simulations, toxicity
