Bisphenol A Binds to Protein Disulfide Isomerase and Inhibits Its Enzymatic and Hormone-Binding Activities

• DOI: 10.1210/en.2005-1235
• Publication Date: 2006-03-17T01:25:16Z
• Authors: Toyoko Hiroi; Kazushi Okada; Susumu Imaoka; Mayuko Osada; Yoshihiko Funae
• Keywords: Male; 0301 basic medicine; Estradiol; Protein Disulfide-Isomerases; Recombinant Proteins; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Phenols; Animals; Triiodothyronine; Benzhydryl Compounds; Carrier Proteins; Protein Binding

Bisphenol A [2,2-bis-(4-hydroxyphenyl) propane; BPA] is a versatile industrial material for plastic products, but increasingly being recognized as pervasive pollutant well. Accumulating evidence indicates that the environmental contaminant BPA one of endocrine-disrupting chemicals potentially can adversely affect humans well wildlife. To define molecular aspects action, we first investigated molecules with which it physically interacts. High BPA-binding activity was detected in P2 membrane fraction prepared from rat brains. As determined by SDS-PAGE analysis, mass protein purified brain 53 kDa. The N-terminal amino acid sequence identical disulfide isomerase (PDI), multifunctional critically involved folding, assembly, and shedding many cellular proteins via its addition to considered function an intracellular hormone reservoir. Kd value binding recombinant PDI 22.6 +/- 6.6 microm. Importantly, L-T3 17beta-estradiol hormones competitively inhibited abolishing activities. In this paper report ubiquitous target propose subsequent inhibition might be mechanistically responsible various actions BPA.