title: Binding of perfluorooctanoic acid to rat liver-form and kidney-form alpha2u-globulins.
abstract: Perfluorooctanoic acid (PFOA) is an organic fluorochemical and is reported to have a long half-life in human blood. Its urinary elimination in rats is markedly sex-dependent, and characterized by significantly longer plasma half-life of PFOA in male rats than in females. It has been postulated that male-specific PFOA binding protein(s) is responsible for the long half-life of PFOA in male rats. In this paper, two male rat specific proteins, liver- and kidney-form alpha2u-globulins (A2U(L) and A2U(K)), were purified from male rat urine and kidney, respectively. The binding of these two nroteins to PFOA was investigated using ligand blotting, electrospray ionization mass spectrometry and fluorescence competitive binding assay. The results revealed that both A2U(L) and A2U(K) were able to bind PFOA in vitro under physiological conditions, and that PFOA and a fluorescent-labeled fatty acid shared the same binding site on both A2U(L) and A2U(K). The binding affinities, however, are relatively weak. The estimated dissociation constants are in the 10(-3) M range, indicating that bindings of PFOA to either A2U(L) or A2U(K) cannot adequately explain the sex-dependent elimination of PFOA in rats, and it is unlikely that PFOA-A2U(K) binding would induce A2U nephropathy as seen with, for example, 1,4-dichlorobenzene.
authors.affiliation: DuPont Haskell Laboratory for Health and Environmental Sciences, Newark, Delaware 19714, USA. xing.han@usa.dupont.com
authors.forename: Xing
authors.initials: X
authors.lastname: Han
authors.forename: Paul M
authors.initials: PM
authors.lastname: Hinderliter
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Snow
authors.forename: Gary W
authors.initials: GW
authors.lastname: Jepson
mesh_terms: D000510:Alpha-Globulins / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002210:Caprylates / Q000378:metabolism*; D005260:Female; D005466:Fluorocarbons / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000209:etiology; D008099:Liver / Q000378:metabolism; D008297:Male; D029362:Organic Anion Transporters, Sodium-Independent / Q000502:physiology; D011485:Protein Binding; D051381:Rats; D012727:Sex Characteristics; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D000510:Alpha-Globulins; D002210:Caprylates; D005466:Fluorocarbons; D029362:Organic Anion Transporters, Sodium-Independent; C088800:Slc22a7 protein, rat; C013803:alpha 2u globulin; C114338:organic anion transport protein 3; C023036:perfluorooctanoic acid