Naslov
Membrane transporters of organic compounds in experimental cadmium nephrotoxicity

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

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

Izvornik
Arhiv za higijenu rada i toksikologiju / - Zagreb, 2012, 14-14

Skup
4th Croatian Congress of Toxicology (CROTOX 2012)

Mjesto i datum
Primošten, Hrvatska, 02.10.2012. - 05.10.2012

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Nije recenziran

Ključne riječi
end-point RT-PCR; heavy metal; immunocytochemistry; kidney; rats; transmission and immunogold cytochemistry; Western blotting

Sažetak
Cadmium nephrotoxicity (Cd-NTX) is manifested by impaired reabsorptive and secretory functions of proximal tubules (PT). The symptoms, that include phosphaturia, proteinuria, aminoaciduria, glucosuria, increased excretion of inorganic and organic anions and cations, polyuria, indicate that Cd targets specific transporters in the PT brush-border (BBM) and basolateral (BLM) membrane. Using subchronic (treatment with CdCl2 for 14 days) and acute (treatment with Cd-metallothionein 6-12 h before sacrifice) experimental models of Cd-NTX in rats, we have studied the expression of representative transporters in the PT cell membranes. Various methods (immunocytochemistry, Western blotting, transmission and immunogold microscopy, end-point RT-PCR) have been applied to characterize the expression of transporters that reside 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 loss of BBM and BLM. In the subchronic model, expression of transporters was downregulated at the level of protein and mRNA. In the acute model we observed a) time-dependent loss of the BBM and BLM transporters, and their accumulation in intracellular vesicles, and b) translocation of NHE3 from the BBM to the BLM. The data indicate that functional defects of PT in Cd-NTX result from a) loss of absorptive and secretory surface, b) loss of transporting proteins in BBM and BLM, and c) loss of cell polarity. In subchronic Cd-NTX, the loss of membrane transporters seems to be mRNA-related, whereas in acute Cd-NTX, the loss of membrane transporters may result from the disrupted intracellular vesicle sorting and trafficking.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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