(283g) Investigation of Cardioprotective Effects of Soy-Derived Phytoestrogens by Proteomic Analysis

Epidemiological observations comparing populations from different ethnic groups and countries suggest that higher consumption of soy-containing foods contributes to the lower incidence of cardiovascular disease in the Asian population than in the American population. Genistein, which constitutes the major part of the total phytoestrogens in soy, is thought to have a potential role in improving risk factors for cardiovascular disease. Although phytoestrogens are generally accepted as beneficial for the cardiovascular system, scientific certainty about the relationship between soy and cardiovascular diseases is still lacking. Several studies have suggested that soy-derived genistein may potentially exert their effects in cardiomyocytes via many means including estrogen receptor-dependent and independent mechanisms. Genistein was also reported to have other cellular effects including inhibition of cell cycle progression, inhibition of angiogenesis, attenuation of oxidant damage, kinase modulation, and regulation of growth factors. Moreover, the biological activity of genistein is likely to vary substantially in dose- and cell type-specific manners. Due to this complex nature of cellular responses to genistein, a more powerful approach to evaluate the mechanism systematically is needed.

Our first study has focused on cultured rat cardiomyocytes as a model system. 2D electrophoresis for both hydrophobic and hydrophilic protein fractions has been employed to compare the protein profiles of genistein-treated and control samples, and differentially expressed proteins have been analyzed by mass spectrometry. More than eighty proteins were shown to be differentially expressed when cardiomyocytes were treated with 1 µM or 50 µM of genistein. In our second study, iTRAQ labeling coupled with a SCX-RP LC-MS shotgun approach is used to compare the protein profiles of genistein-treated and control cardiac muscle tissue samples from SD rats with and without ischemic preconditioning. Results from IMAC-based phosphopeptide enrichment method development for cardiac tissue will also be discussed.