Naslov
Brush-border and basolateral transporters of organic compounds in acute and subchronic models of experimental cadmium nephrotoxicity in rats

Autori
Sabolić, Ivan ; Ljubojević, Marija ; Breljak, Davorka ; Herak-Kramberger, Carol M ; Anzai, Naohiko ; Koepsell, Hermann

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

Izvornik
Arhiv za higijenu rada i toksikologiju 64(2) / Kopjar, Nevenka - Zagreb : Institut za medicinska istraživanja i medicinu rada, 2013, 349-349

Skup
1. hrvatski simpozij o transporterima SOT-1

Mjesto i datum
Zagreb, Hrvatska, 06.06.2013. - 07.06.2013

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
heavy metal toxicity; immunocytochemistry; kidney; mRNA expression; transmission electron microscopy; protein expression; proximal tubule; RT-PCR; Western blotting

Sažetak
Cadmium nephrotoxicity (Cd-NTX) manifests itself through impaired proximal tubule (PT) reabsorptive and secretory functions. Urine symptoms (phosphaturia, proteinuria, aminoaciduria, glucosuria, increased excretion of inorganic and organic anions and cations, polyuria) indicate that Cd affects various transporters in the PT brush-border (BBM) and basolateral (BLM) membranes. In order to investigate their expression in Cd-NTX, we exploited experimental models of subchronic (treatment with CdCl2 for 14 days) and acute (treatment with Cd-metallothionein 6 h to 12 h before sacrifice) Cd-NTX in rats. Immunocytochemistry, Western blotting, transmission electron microscopy, and end-point RT-PCR were applied to screen transporters located in the PT BBM (NaPi2, V-ATPase, NHE3, Sglt1, Sglt2), BLM (Na/K-ATPase, Oat1, Oat3, Oct1, Oct2), or in both membranes (AQP1). In both models, PT exhibited a loss of BBM and BLM. In the subchronic model, the expression of various transporters was strongly downregulated at both the protein and mRNA level. In the acute model we observed a time-dependent loss of BBM and BLM transporters and their redistribution in intracellular organelles, translocation of certain transporters (NHE3) from the BBM to the BLM, and minimal changes in the expression of mRNAs. The data indicate that functional defects of PT in Cd-NTX result from the loss of 1) absorptive and secretory surface, 2) transporting proteins in BBM and BLM, and 3) cell polarity. In subchronic Cd-NTX, the loss of membrane transporters is mRNA-related, whereas in acute Cd-NTX, their loss may result from the disrupted intracellular vesicle sorting and trafficking.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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