Hydroxylated polychlorinated biphenyls (PCBs) interact with protein disulfide isomerase and inhibit its activity.
Protein disulfide isomerase (PDI) is a catalyst of isomerization of substrate protein intra- and extra-molecular disulfide bridges and also has 3,3',5-triiodo-l-thyronine (T(3))-binding activity and molecular chaperone-like activity. We previously found that halogenated derivatives of bisphenol A as well as bisphenol A itself bind to PDI and thereby suppress the oxidative refolding of reduced RNaseA by PDI. Polychlorinated biphenyls (PCBs) are environmental endocrine-disrupting chemicals that cause various abnormalities in many organs such as the central nervous system. PCBs are metabolized to hydroxylated compounds (HO-PCBs) in humans and other animals, and HO-PCBs gain toxicity by metabolism. In the present study, 2',3,3',4',5'-pentachlorobiphenyl (penCB), 2',3,3',5,5',6'-hexachlorobiphenyl (hexCB), and their 4-hydroxylated metabolites (HO-penCB and HO-hexCB, respectively) were used to examine whether they interact with PDI and inhibit its activity. HO-penCB and HO-hexCB markedly inhibited the binding of T(3) to PDI. However, nonhydroxylated PCBs did not show any interaction with PDI. The effects of PCBs and HO-PCBs on PDI activity were also investigated using an RNaseA refolding assay. Both HO-PCBs inhibited the oxidative refolding of reduced RNaseA by PDI. We also assessed the effects of HO-PCBs and PCBs on the chaperone activity of PDI, which was measured by a thermal aggregation assay, and found that neither HO-PCBs nor PCBs have significant inhibitory or promoting effects. These findings suggest that the metabolites of PCBs have the potential to cause defective protein folding via PDI.
Nanobiotechnology Research Center and Department of Bioscience, School of Science and Technology, Kwansei Gakuin University, 2-1 Gakuen, Sanda, Hyogo 669-1337, Japan. bhp46831@kwansei.ac.jp
Kazushi
K
Okada
Shoko
S
Hashimoto
Yoshihiko
Y
Funae
Susumu
S
Imaoka
D000818:Animals; D045744:Cell Line, Tumor; D006900:Hydroxylation; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D017510:Protein Folding; D051381:Rats
D011078:Polychlorinated Biphenyls; D019704:Protein Disulfide-Isomerases