WATANABE Yoko, Ph.D. / Assistant Professor
Division of Pharmaceutical Health Biosciences
Department of Pharmaceutical Sciences
1. Metabolic modification of nuclear receptors caused by environmental chemicals.
2. Effect of environmental chemicals on transcriptional activities of nuclear receptors.
Nuclear receptor transcriptional activities of various environmental chemicals are metabolically activated. For example, the estrogen receptor (ER) and antiandrogen receptor transcriptional activities of Benzophenone-3, a representative UV absorbant, are activated by oxidative metabolism. In contrast, the ERα and ERβ agonistic activities of butylparaben (used as antimicrobial agents) may be diminished by carboxylesterase. Indeed, 4-hydroxybenzoic acid itself showed little estrogenic activity. PPARs are involved in variety of disease conditions, such as obesity and metabolic syndrome.
1. Fujino C, Watanabe Y, Sanoh S, Hattori S, Nakajima H, Uramaru N, Kojima H, Yoshinari K, Ohta S, Kitamura S. Comparative study of the effect of 17 parabens on PXR-, CAR- and PPARα-mediated transcriptional activation. Food Chem.Toxicol., 133, 110792 (2019).
2. Fujino C, Tamura Y, Tange S, Nakajima H, Sanoh S, Watanabe Y, Uramaru N, Kojima H, Yoshinari K, Ohta S, Kitamura S. Metabolism of methiocarb and carbaryl by rat and human livers and plasma, and effect on their PXR, CAR and PPARα activities. J Toxicol Sci., 41, 677-691, (2016).
3. Watanabe Y., Kojima H., Takeuchi S., Uramaru N., Sanoh S., Sugihara K., Kitamura S., Ohta S., Metabolism of UVfilter benzophenone-3 by rat and human liver microsomes and its effect on endocrine-disrupting activity. Toxicol. Appl. Pharmacol., 282, 119-128 (2015).
4. Watanabe Y., Kojima H., Takeuchi S., Uramaru N., Ohta S., Kitamura S., Comparative study ontranscriptional activity of 17parabens mediated by estrogen receptor α and β and androgen receptor. Food Chem.Toxicol., 57, 227-234 (2013).