title: Expression of basolateral organic anion and cation transporters in experimental cadmium nephrotoxicity in rat kidney.
abstract: Cadmium (Cd)-intoxicated experimental animals exhibit impaired renal secretion of organic anions (OA) and cations (OC), indicating their transporters (Oats and Octs) in the proximal tubule (PT) basolateral membrane as possible targets of Cd. To correlate transport data from the literature with the expression of relevant transporters, we performed immunochemical and RT-PCR studies of renal Oats and Octs in the subchronic (treatment with CdCl2; 2 mg Cd/kg b.m./day, for 2 weeks) and acute (treatment with Cd-metallothionein (CdMT); 0.4 mg Cd/kg b.m., 6 or 12 h before killing) models of Cd nephrotoxicity. In the subchronic model, PT exhibited a minor loss of basolateral invaginations and overall unchanged expression of Na(+)/K(+)-ATPase and GAPDH proteins and mRNAs, while the expression of Oat and Oct proteins and their mRNAs was strongly downregulated. In the acute model, a time-related redistribution of basolateral transporters to the intracellular vesicular compartment was a major finding. However, 6 h following CdMT treatment, the total abundance of Oat and Oct proteins in the renal tissue remained unchanged, the expression of mRNAs decreased only for Oats, while a limited Oat1 and Na(+)/K(+)-ATPase immunoreactivity in the PT apical membrane indicated loss of cell polarity. As tested in rats treated with colchicine, the observed loss/redistribution of basolateral transporters in both models may be independent on microtubules. Therefore, the diminished renal secretion of OA and OC via PT in Cd nephrotoxicity may result from (a) limited loss of secretory surface (basolateral invaginations), (b) selective loss of Oats and Octs, and
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
authors.forename: Marija
authors.initials: M
authors.lastname: Ljubojević
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
authors.forename: Davorka
authors.initials: D
authors.lastname: Breljak
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia.
authors.forename: Carol M
authors.initials: CM
authors.lastname: Herak-Kramberger
authors.affiliation: Department of Pharmacology and Toxicology, Dokkyo Medical University School of Medicine, Tochigi, 321-0293, Japan.
authors.forename: Naohiko
authors.initials: N
authors.lastname: Anzai
authors.affiliation: Molecular Toxicology Unit, Institute for Medical Research and Occupational Health, Ksaverska cesta 2, 10000, Zagreb, Croatia. sabolic@imi.hr.
authors.forename: Ivan
authors.initials: I
authors.lastname: Sabolić
mesh_terms: D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D050482:Catecholamine Plasma Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008297:Male; D008668:Metallothionein / Q000633:toxicity; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D023382:Toxicity Tests, Acute; D059550:Toxicity Tests, Subchronic
chemical_list: D050482:Catecholamine Plasma Membrane Transport Proteins; D027362:Organic Anion Transport Protein 1; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C493212:Slc22a1 protein, rat; C421043:Slc22a6 protein, rat; C004203:cadmium-binding protein; D002104:Cadmium; D008668:Metallothionein; D000254:Sodium-Potassium-Exchanging ATPase
keywords: Heavy metal toxicity; Immunocytochemistry; Kidney; Membrane transporters; Organic anions and cations; RT-PCR; SLC22 family; Western blotting