Yang Ya-Di, Tian Rong, Lu Naihao
College of Chemistry and Chemical Engineering, Jiangxi Key Laboratory of Green Chemistry, Jiangxi Normal University, Nanchang 330022, China.
College of Chemistry and Chemical Engineering, Jiangxi Key Laboratory of Green Chemistry, Jiangxi Normal University, Nanchang 330022, China.
Sci Total Environ. 2023 Jun 10;876:162738. doi: 10.1016/j.scitotenv.2023.162738. Epub 2023 Mar 10.
With the ubiquitous applications of perfluorinated compounds such as perfluorooctanoic acid (PFOA) in industrial and commercial products, the toxicity of these engineered materials in environmental and public health is received growing attention. As a typical organic pollutant, PFOA has been extensively found in wildlife and human bodies, and can preferentially bind to serum albumin in vivo. However, the importance of protein-PFOA interactions on the cytotoxicity of PFOA could not be stressed enough. In this study, we used both experimental and theoretical approaches, to investigate the interactions of PFOA with bovine serum albumin (BSA, the most abundant protein in blood). It was found that PFOA could mainly interact with Sudlow site I of BSA to form BSA-PFOA complex, in which van der Waals forces and hydrogen bonds played dominant roles. Moreover, the strong binding of BSA could greatly alter the cellular uptake and distribution of PFOA in human endothelial cells, and result in the decreases of reactive oxygen species formation and cytotoxicity for these BSA-coated PFOA. Consistently, the addition of fetal bovine serum into cell culture medium also significantly mitigated PFOA-induced cytotoxicity, which was attributed to the extracellular complexation between PFOA and serum proteins. Altogether, our study demonstrates that the binding of serum albumin to PFOA could reduce its toxicity by affecting the cellular responses.
随着全氟辛酸（PFOA）等全氟化合物在工业和商业产品中的广泛应用，这些工程材料对环境和公众健康的毒性受到越来越多的关注。作为一种典型的有机污染物，PFOA已在野生动物和人体中广泛发现，并且在体内可优先与血清白蛋白结合。然而，蛋白质 - PFOA相互作用对PFOA细胞毒性的重要性再怎么强调也不为过。在本研究中，我们采用实验和理论方法，研究了PFOA与牛血清白蛋白（BSA，血液中最丰富的蛋白质）的相互作用。结果发现，PFOA主要与BSA的Sudlow位点I相互作用形成BSA - PFOA复合物，其中范德华力和氢键起主导作用。此外，BSA的强烈结合可极大地改变PFOA在人内皮细胞中的细胞摄取和分布，并导致这些BSA包被的PFOA的活性氧形成和细胞毒性降低。同样，向细胞培养基中添加胎牛血清也显著减轻了PFOA诱导的细胞毒性，这归因于PFOA与血清蛋白之间的细胞外络合。总之，我们的研究表明血清白蛋白与PFOA的结合可通过影响细胞反应来降低其毒性。
