Naslov
Renal expression of organic anion transporters Oat1 and Oat3 is downregulated after treating rats with cadmium, mercury and cisplatin

Autori
Ljubojevic, Marija ; Breljak, Davorka ; Anzai, Naohiko ; Sabolic, Ivan

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum biologorum, Final Programme and Abstract Book / Banfić, H ; Boban, M ; Francetić, I ; Klarica, M ; Muck-Šeler, D ; Pivac, N ; Sabolić, I ; Tvrdeić, A ; Župan, G. - Zagreb : Hrvatsko prirodoslovno društvo, 2007, Vol. 109 (Suppl. 2) 149-149

Skup
5th CROATIAN CONGRESS OF PHARMACOLOGY and 2nd CONGRESS OF CROATIAN PHYSIOLOGICAL SOCIETY

Mjesto i datum
Osijek, Hrvatska, 19.09.2007. - 22.09.2007

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
toxic metals; nephrotoxicity; organic anion transporters

Sažetak
Previous studies have shown that treating rats or mice with some nephrotoxic metals (NTM) inhibited renal transport/secretion of organic anion (OA) p-aminohippurate (PAH) and its accumulation in incubated kidney cortex slices. Moreover, nephrotoxicity of these metals was prevented by probenecid, a compound that inhibits the transport of various OA, including PAH, thus indicating a possible interaction of NTM and OA at the level of membrane transporters. Major PAH transporters in the mammalian kidney have recently been cloned and characterized, and include Oat1 and Oat3 proteins localized to the basolateral membrane (BLM) of proximal tubule (PT) cells. The interaction between NTM and Oat1 and Oat3, that inhibits PAH secretion, has not been clarified. The aim of this study was to establish if cadmium (Cd), mercury (Hg), and cisplatin (cisPt) affected the expression of PAH transporters Oat1 and Oat3 at the protein and mRNA levels. We compared the expression of these transporters in vehicle-treated male rats (control) with that in rats treated with CdCl2 (2 mg Cd/kg b.m., s.c., daily for 2 weeks), HgCl2 (a single dose of 1 mg Hg/kg b.m., s.c., daily for 2 days) or cisPt (a single dose of 5 mg cisPt/kg b.m., i.p., 5 days before sacrifice). The methods applied were immunobloting (IB) in isolated total cell membranes (TCM) from the kidney cortex, immunocytochemistry (IC) in frozen kidney tissue sections, and RT-PCR with renal cortical tissue mRNA. IB and IC studies were performed using specific polyclonal antibodies, whereas RT-PCR was performed using commercial mRNA probes for specific transporters. In IB studies, the abundance of Oat1 and Oat3 proteins in TCM from the cortex of NTM-treated rats significantly decreased (Cd>Hg>cisPt). In IC studies, both transporters were localized to the PT BLM in control animals, exhibiting different intensities in specific PT segments (Oat1: S2>S3, negative S1 ; Oat3: S1=S2, negative S3). In the NTM-treated rats, the staining intensity for both transporters clearly diminished in the sequence Cd>Hg>cisPt. In addition, heavily damaged cells and loss of BLM invaginations were observed in S1 and S2 of Cd-treated rats, and in S3 of Hg- and cisPt-treated rats. In RT-PCR studies, the expression of mRNA for both transporters was downregulated strongly in Cd- and Hg-treated, and weakly in cisPt-treated rats. To conclude, previously observed inhibition of the renal PAH secretion/transport in NTM-treated animals may result from: a) loss of the PT BLM (transporting membrane surface), and b) loss of Oat1 and Oat3 protein (transporting proteins for PAH) in the PT BLM.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Temeljne medicinske znanosti

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