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Nutrient-Gene Interactions

Hepatic Cytochrome p450-2A and Phosphoribosylpyrophosphate Synthetase-Associated Protein mRNA Are Induced in Gerbils after Consumption of Isoflavone-Containing Protein^{1 ,,2}

Orsolya Mezei^*, Chris N. Chou, Kathleen J. Kennedy, Claudia Tovar-Palacio and Neil F. Shay^*3

^* Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556 and Department of Food Science and Human Nutrition, University of Illinois, Urbana, IL 61801

³To whom correspondence should be addressed. E-mail: nshay1{at}nd.edu.

Soy intake reduces cholesterol levels, but neither the exact component in soy causing this reduction nor the mechanism by which cholesterol is reduced is known with certainty. In this study, a genetic screen was performed to identify hepatic mRNA in gerbils regulated by soy or soy isoflavones. Gerbils were fed casein, an alcohol-washed soy-based diet (containing low levels of isoflavones), and the soy-based diet supplemented with an isoflavone-containing soy extract. After feeding for 28 d, gerbils were killed, hepatic RNA was isolated, and genes that were differentially expressed in any of the three dietary conditions were identified. Fifteen different mRNA were originally selected, including two mRNA that were studied further and shown to be highly regulated. Messenger RNA levels for both cytochrome P450-2A and phosphoribosylpyrophosphate synthetase-associated protein were up-regulated in a dose-dependent manner when soy replaced casein in the diet at 0, 33, 67 and 100% of original casein levels. A subsequent experiment used purified amino acid mixtures resembling the percentage amino acid composition of soy and casein to ensure that isoflavone-free protein sources could be tested. Using these mixtures, a 2 x 2 x 2 design tested: natural vs. synthetic protein sources, casein- vs. soy-based diets, and isoflavone extract-supplemented or supplement-free diets. This design demonstrated that these two mRNA were again significantly up-regulated more than twofold (P < 0.05) in gerbils fed all diets containing isoflavones. Induction of these two mRNA by soy may be due to the aryl hydrocarbon receptor element in the promoter region of both genes.

KEY WORDS: • soy • isoflavones • gene expression • cholesterol • mRNA

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