In vitro fluorescence displacement investigation of thyroxine transportdisruption by bisphenol A
Jie Cao , Liang-Hong Guo , Bin Wan , Yin Wei
DOI:
Received March 29, 2010,Revised May 18, 2010, Accepted , Available online
Volume 23,2011,Pages 315-321
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Bisphenol A (BPA) is a chemical with high production volume and wide applications in many industries. Although BPA is known
as an endocrine disruptor, its toxic mechanisms have not been fully characterized. Due to its structural similarity to thyroid hormones
thyroxine (T4) and triiodothyronine (T3), one possible mechanism of BPA toxicity is disruption of hormone transport by competitive
binding with the transport proteins. In this study, the binding interactions of BPA, T4, and T3 with three thyroid hormone transport
proteins, human serum albumin (HSA), transthyretin (TTR), and thyroxine-binding globulin (TBG) were investigated by fluorescence
measurement. Using two site-specific fluorescence probes dansylamide and dansyl-L-proline, the binding constants of BPA with HSA
at drug site I and site II were determined as 2.90 104 and 3.14 104 L/mol, respectively. By monitoring the intrinsic fluorescence
of tryptophan, a binding constant of 4.70 103 L/mol was obtained. Similarly, by employing 8-anilino-1-naphthalenesulfonic acid as
fluorescence probe, the binding a nity of BPA with TTR and TBG was measured to be 3.10 105 and 5.90 105 L/mol, respectively.
In general, BPA showed lower binding a nity with the proteins than T3 did, and even lower a nity than T4. Using these binding
constants, the amount of BPA which would bind to the transport proteins in human plasma was estimated. These results suggest that
the concentrations of BPA commonly found in human plasma are probably not high enough to interfere with T4 transport.
