Recombinant Albumin and Transthyretin Transport Proteins from Two Gull Species and Human: Chlorinated and Brominated Contaminant Binding and Thyroid Hormones

Abstract

Environmentally relevant concentrations of selected polychlorinated biphenyl (PCB) and polybrominated diphenyl ether (PBDE) flame retardant congeners and their hydroxylated (OH) and methoxylated (MeO) analogues that can perturb thyroid hormone-dependent processes were comparatively examined with respect to competitive binding with thyroxine (T(4)) and 3,5,3'-triiodothyronine (T(3)) thyroid hormones (THs) on recombinant human and gull albumin and transthyretin transport proteins. The liver tissue was from glaucous gulls (Larus hyperboreus) from Norway and herring gulls (Larus argentatus) from the Great Lakes of North America. We isolated, cloned, sequenced, purified, and expressed the cDNA (cDNA) of albumin from liver of herring and glaucous gull. Albumin amino acid sequences were identical for both gull species. Concentration-dependent, competitive binding curves were generated for T(4) and T(3) binding alone and for selected substrates using gull and human recombinant albumin (recALB). Human recALB had high preference for T(4) relative to T(3), whereas it was reversed for gull recALB. Binding assays with recALB and recTTR gull proteins showed that relative to 2,2',4,4'-tetrabromoDE (BDE-47) and 2,2',3,4',5,5',6-heptaCB (CB-187) and the MeO-substituted (4-MeO-CB187 and 6-MeO-BDE47) analogues, 4-OH-CB187, 6-OH-BDE47, and 4'-OH-BDE49 had the greatest binding affinity and potency, and that competitive binding was greater for T(3) relative to T(4). These results indicate that xenobiotic ligand binding to human ALB or TTR cannot be used as a surrogate for gull binding interactions. The combination of TH-like brominated diphenyl ether backbone (relative to the chlorinated biphenyl backbone), and the presence of OH-group produced a more effective competitive ligand on human and gull recALB and recTTR relative to both T(3) and T(4). This suggests the possibility that OH-substituted organohalogen contaminants may be an exposure concern to the thyroid system in free-ranging gulls as well as for humans.

Phytotoxicity of Brominated Diphenyl Ether-47 (BDE-47) and Its Hydroxylated and Methoxylated Analogues (6-OH-BDE-47 and 6-MeO-BDE-47) to Maize (Zea mays L.)

“…19 Furthermore, it has been reported that 6-OH-BDE-47 has a greater affinity than either BDE-47 or 6-MeO-BDE-47 for transport protein transthyretin, inducing a decrease in plasma thyroid hormone thyroxine levels. 17,20 Results obtained from in vitro exper-imentation and molecular dynamics simulation demonstrated that OH-PBDEs displayed greater estrogenicities than their corresponding PBDEs and MeO-PBDEs analogues, which was especially true for 6-OH-BDE-47. 21 Although research on the toxic effects of PBDEs, OH-PBDEs, and MeO-PBDEs has shown great progress, most studies have focused on their neurotoxicity, endocrine disruption, and genotoxicity on aquatic species and mammals.…”

Effect of reduced food intake on toxicokinetics of halogenated organic contaminants in herring gull (Larus argentatus) chicks

“…In conclusion, the results of the present study show that reduced food intake mobilizes a wide range of HOCs to organs of toxicological sensitivity such as brain and liver. Second, the results indicate that enzyme induction increases de novo synthesis of OH-PCBs (and possibly other contaminant metabolites), which have greater toxicological impacts compared to parent POPs, for example, toward the thyroid system [12,13].…”

“…Some OH and MeSO 2 metabolites are retained in the body, and their toxic potential toward the endocrine system is higher than that of the parent compounds [10,11]. For example, some OH-PCBs show structural similarities to thyroid hormones, and may have a higher affinity to thyroid hormone transport proteins in seabirds than thyroid hormones [12,13].…”

The effects of early postnatal exposure to a low dose of decabromodiphenyl ether (BDE-209) on serum metabolites in male mice

“…Brominated dioxin/furan (PBDD/Fs) have been detected as photochemical degradation products of PBDEs, and the detection of debrominated and hydroxylated metabolites of PBDEs has been reported in previous studies (WHO, 1998;Meerts et al, 2001;Ucán-Marin et al, 2010). It was reported that decreased spermatogenic activity in the testes and defective or necrotic spermatocytes in the epididymis were found in Wistar rats following daily oral administration of brominated dioxin (WHO, 1998).…”