Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells英文文献资料.docVIP

Advances in Biological Chemistry, 2012, 2, 92-105 ABC /10.4236/abc.2012.22012 Published Online May 2012 (http://www.SciRP.org/journal/abc/) Apoptosis-inducing activity of endocrine-disrupting chemicals in cultured PC12 cells Harue Sasaya 1,2 , Kazuya Yasuzumi , Hiroki Maruoka 1 1,3 , Ayumi Fujita 1 , Yuichi Kato 1 , Taiki Waki 1 , 1 1* Koji Shimoke , Toshihiko Ikeuchi 1 Department of Life Science and Biotechnology, Faculty of Chemistry, Materials and Bioengineering and Strategic Research Base, Kansai University, Osaka, Japan 2 Division of Natural Products Chemistry, Institute of Natural Medicine, University of Toyama, Toyama, Japan Technology Research Laboratory, Kurabo Industries Ltd., Osaka, Japan 3 Email: ikeuchi@kansai-u.ac.jp * Received 20 January 2012; revised 9 February 2012; accepted 29 February 2012 ABSTRACT Keywords: Endocrine-Disrupting Chemicals; ER Stress; Apoptosis; Estrogen Receptor; PC12 Cells Endocrine-disrupting chemicals (EDCs) are known to exert estrogen-like effects that are similar to those made by naturally produced hormones or by inhibi- tion of the receptors in the cell receiving the hor- mones. Recently, several reports have indicated that EDCs can affect the developing central nervous sys- tem. In our current study, we report that some EDCs induce apoptosis in cultured PC12 cells and can be classified into three groups. Bisphenol A (BPA), p- nonylphenol (NP) and tributyltin chloride (TBT) were found to induce endoplasmic reticulum (ER) stress-associated apoptosis and activate the unfolded protein response (UPR) system, whereas benomyl (beno) induced non-ER stress-associated apoptosis. The half-maximal apoptosis-inducing concentrations (IC50) of these EDCs were 160 μM for BPA, 25.6 μM for NP, 640 nM for TBT and 48 μM for beno. Al- though these concentrations are higher than those found in