Naslov
Mechanism of proteinuria in cadmium-intoxicated rats

Autori
Sabolić, Ivan ; Herak-Kramberger, Carol Mirna ; Brown, Dennis

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

Izvornik
Program and Abstract Book / European Kidney Research Forum - Bergamo : European Kidney Research Forum, 1996

Skup
2nd European Kidney Research Forum (EKRF)

Mjesto i datum
Bergamo, Italija; Baveno, Italija, 24.05.1996. - 27.05.1996

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
proteinuria; vacuolar ATPase; endocytosis; cadmium; kidney; rat

Sažetak
MECHANISM OF PROTEINURIA IN CADMIUM-INTOXICATED RATS Sabolic I., C. M. Herak-Kramberger, and D. Brown, IMI, Zagreb, Croatia, and Renal Unit, MGH, Boston, USA. Cadmium (Cd)-intoxicated rats exhibit a marked polyuria, phosphaturia, and proteinuria. We have investigated cellular causes of the Cd-induced proteinuria. Following perfusion with the FITC-dextran in vivo, the Cd-treated rats (2 mg Cd/kg B.W., s.c. for 14 days) exhibited (i) a strongly diminished uptake of this fluid-phase marker into renal proximal tubule cells (PTC) and (ii) randomly scattered endosomes in the cell cytoplasm, thus indicating an impaired vesicle trafficking via endo- and exocytosis. Cd may affect endocytosis by inhibiting the V-type H+-ATPase in the cell organelles; the immunohistochemical studies in frozen sections of the fixed kidney cortex and the Western blot studies in brush-border membrane vesicles from the renal cortex showed a strong decrease of the 31 kD and 70 kD H+-ATPase subunits antigenicity in samples from Cd-treated rats. As measured by the Pi liberation assay, the bafilomycin sensitive ATPase in the PTC brush-border membrane was drastically inhibited by Cd in vivo and in vitro. In addition, the acridine orange fluorescence quench experiments in isolated renal cortical endocytic vesicles revealed that Cd dissipated the transmembrane DpH by increasing H+ conductance of the vesicle membrane. We conclude that proteinuria in Cd-intoxicated rats may result from a limited endocytosis of the filtered proteins due to impaired acidification mechanisms in the PTC organelles.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA