Interactions of flurochemicals with rat liver fatty acid-binding protein
Interactions of flurochemicals with rat liver fatty acid-binding protein
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DOI：
10.1016/s0300-483x(02)00081-1
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发表时间：
2002-07-15
期刊：
影响因子：
4.5
通讯作者：
Seacat, AM
中科院分区：
文献类型：
--
作者：
Luebker, DJ;Hansen, KJ;Seacat, AM
肝脏脂肪酸结合蛋白（L-FABP）是一种丰富的细胞内脂质载体蛋白。测试了以下假设：全氟辛烷磺酸 (PFOS)、全氟辛酸 (PFOA) 和某些相关的全氟辛烷磺酰胺基含氟化合物 (PFOSA) 会干扰 L-FABP 对脂肪酸的结合亲和力。 PFOA、PFOS、N-乙基全氟辛烷磺酰胺 (N-EtFOSA)、N-乙基全氟辛烷磺酰胺乙醇 (N-EtFOSE) 和强过氧化物酶体增殖剂 Wyeth-14643 (WY) 抑制 11-(5-二甲基氨基萘磺酰基)-十一烷酸 (DAUDA) 与 -L-FABP 结合的相对有效性为确定。 DAUDA-L-FABP 复合物的解离常数 (Kd) 为 0.47 nM。在竞争性结合测定中，PFOS 对 DAUDA-L-FABP 结合表现出最高水平的抑制作用，其次是 N-EtFOSA、WY，以及具有相同 IC(50) 的 N-EtFOSE 和 PFOA。本研究中提供的体外数据支持以下假设：这些含氟化合物可能会干扰脂肪酸或其他内源配体与 L-FABP 的结合。此外，这项工作提供了证据支持以下假设：L-FABP 内源配体的置换可能导致喂食这些含氟化合物的啮齿动物产生毒性。 (C) 2002 Elsevier Science Ireland Ltd. 保留所有权利。
Liver-fatty acid binding protein (L-FABP) is an abundant intracellular lipid-carrier protein. The hypothesis that perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and certain related perfluorooctanesulfonamide-based fluorochemicals (PFOSAs) can interfere with the binding affinity of L-FABP for fatty acids was tested. The relative effectiveness of PFOA, PFOS, N-ethylperfluorooctanesulfonamide (N-EtFOSA), N-ethylperfluorooctanesulfonamido ethanol (N-EtFOSE), and of the strong peroxisome proliferator Wyeth-14643 (WY) to inhibit 11-(5-dimethylaminonapthalenesulphonyl)-undecanoic acid (DAUDA) binding to-L-FABP was determined. The dissociation constant (Kd) of the DAUDA-L-FABP complex was 0.47 nM. PFOS exhibited the highest level of inhibition of DAUDA-L-FABP binding in the competitive binding assays, followed by N-EtFOSA, WY, and, with equal IC(50)s, N-EtFOSE and PFOA. The in vitro data presented in this study support the hypothesis that these fluorochemicals may interfere with the binding of fatty acids or other endogenous ligands to L-FABP. Furthermore, this work provides evidence to support the hypothesis that displacement of endogenous ligands from L-FABP may contribute to toxicity in rodents fed these fluorochemicals. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.