DETERMINING THE MOLECULAR INTERACTIONS OF PERFLUORINATED CARBOXYLIC ACIDS WITH HUMAN SERA AND ISOLATED HUMAN SERUM ALBUMIN USING NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY

被引:79
作者
D'eon, Jessica C. [2 ]
Simpson, Andre J. [1 ]
Kumar, Rajeev [1 ]
Baer, Andrew J. [1 ]
Mabury, Scott A. [2 ]
机构
[1] Univ Toronto, Scarborough Coll, Dept Chem, Toronto, ON M1C 1A4, Canada
[2] Univ Toronto, Dept Chem, Toronto, ON M5S 3H6, Canada
基金
加拿大自然科学与工程研究理事会;
关键词
Perfluorinated carboxylic acid; Perfluorooctaonic acid; Perfluorohexanoic acid; Serum albumin; Sudlow's drug binding sites; TRANSFER DIFFERENCE NMR; BINDING-SITES; POLYFLUOROALKYL CHEMICALS; PERFLUOROCARBOXYLIC ACIDS; PERFLUOROOCTANOIC ACID; OCCUPATIONAL-EXPOSURE; PERFLUOROALKYL ACIDS; CRYSTAL-STRUCTURE; RENAL TRANSPORT; FATTY-ACIDS;
D O I
10.1002/etc.204
中图分类号
X [环境科学、安全科学];
学科分类号
08 ; 0830 ;
摘要
Perfluorooctanoate (PFOA) is ubiquitous in North American human sera and has a serum half-life of 3.5 years in humans. The molecular interactions that lead to the bioaccumulation of these hydrophobic and lipophobic molecules in human blood are not well understood. Perfluorohexanoic acid (PFHxA) and PFOA were used as model perfluorinated carboxylic acids (PFCAs) to characterize the major site of PFCA interaction in human sera. Using novel heteronuclear saturation transfer difference nuclear magnetic resonance spectroscopy experiments, human serum albumin (HSA) was identified as the major site of interaction for both PFHxA and PFOA in human sera. Heteronuclear single quantum coherence nuclear magnetic resonance experiments were then performed to interrogate site-specific interactions of PFHxA and PFOA with isolated HSA. Perfluorohexanoic acid was found to bind specifically to Sudlow's drug-binding site II, whereas PFOA interacted preferentially with Sudlow's drug-binding site I at the lower concentration, with additional interactions developing at the higher concentration. These experiments highlight the utility of nuclear magnetic resonance spectrometry as a tool to observe the in situ interactions of chemical contaminants with biological systems. Both PFCAs displaced the endogenous HSA ligand oleic acid at concentrations lower than observed for the drugs ibuprofen and phenylbutazone, which are established HSA ligands. Interactions between PFCAs and HSA may affect the pharmacokinetics and distribution of fatty acids and certain drugs in the human body and warrant further investigation. Environ. Toxicol. Chem. 2010;29:1678-1688. (C) 2010 SETAC
引用
收藏
页码:1678 / 1688
页数:11
相关论文
共 52 条
[1]   Perfluoroalkyl acids and related chemistries - Toxicokinetics and modes of action [J].
Andersen, Melvin E. ;
Butenhoff, John L. ;
Chang, Shu-Ching ;
Farrar, David G. ;
Kennedy, Gerald L., Jr. ;
Lau, Christopher ;
Olsen, Geary W. ;
Seed, Jennifer ;
Wallacekj, Kendall B. .
TOXICOLOGICAL SCIENCES, 2008, 102 (01) :3-14
[2]  
[Anonymous], 1995, ALL ALBUMIN
[3]   Crystallographic analysis reveals common modes of binding of medium and long-chain fatty acids to human serum albumin [J].
Bhattacharya, AA ;
Grüne, T ;
Curry, S .
JOURNAL OF MOLECULAR BIOLOGY, 2000, 303 (05) :721-732
[4]   Structure-Activity Relationships and Human Relevance for Perfluoroalkyl Acid-Induced Transcriptional Activation of Peroxisome Proliferation in Liver Cell Cultures [J].
Bjork, James A. ;
Wallace, Kendall B. .
TOXICOLOGICAL SCIENCES, 2009, 111 (01) :89-99
[5]   The impact of plasma protein binding on the renal transport of organic anions [J].
Bow, DAJ ;
Perry, JL ;
Simon, JD ;
Pritchard, JB .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 316 (01) :349-355
[6]   Concerning the origin of 19F-19F NMR COSY and NOESY connections in the spectra of perfluorooctanoic acid, RF-palmitic acid-F13 and diethyl perfluorosuberate [J].
Buchanan, GW ;
Munteanu, E ;
Dawson, BA ;
Hodgson, D .
MAGNETIC RESONANCE IN CHEMISTRY, 2005, 43 (07) :528-534
[7]   Polyfluoroalkyl chemicals in the US population: Data from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and comparisons with NHANES 1999-2000 [J].
Calafat, Antonia M. ;
Wong, Lee-Yang ;
Kuklenyik, Zsuzsanna ;
Reidy, John A. ;
Needham, Larry L. .
ENVIRONMENTAL HEALTH PERSPECTIVES, 2007, 115 (11) :1596-1602
[8]   Thirty Years of Medical Surveillance in Perfluooctanoic Acid Production Workers [J].
Costa, Giovanni ;
Sartori, Samantha ;
Consonni, Dario .
JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL MEDICINE, 2009, 51 (03) :364-372
[9]   Distribution of organobrominated and organochlorinated contaminants in Belgian human adipose tissue [J].
Covaci, A ;
de Boer, J ;
Ryan, JJ ;
Voorspoels, S ;
Schepens, P .
ENVIRONMENTAL RESEARCH, 2002, 88 (03) :210-218
[10]   Fatty acid binding to human serum albumin: new insights from crystallographic studies [J].
Curry, S ;
Brick, P ;
Franks, NP .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 1999, 1441 (2-3) :131-140