engleski

The structure of microtubules in liver and kidney cells is deranged in cadmium-intoxicated rats

Chronic cadmium (Cd) intoxication in man and experimental animals is manifested by defects in reabsorptive and secretory functions of the renal proximal tubule (PT). Polyuria, glucos-uria, aminoaciduria, phosphaturia, and proteinuria are common signs of Cd nephrotoxicity whose mechanisms are poorly understood at the cellular level. In the cell, Cd may affect microtubules whose arrangement and function are responsible for vesicle trafficking between the plasma membrane (PM) and intracellular organelles (endo- and exocytosis). An impaired endo- and exocytosis due to microtubule derangement may lead to proteinuria and diminished cellular uptake of solutes due to a loss of specific transporters in the PM. We studied endocytosis and microtubules in the liver and kidney cells in control and Cd-treated (2 mg Cd/kg B.W., s.c., daily for 14 days) rats. As measured by the atomic absorption spectrometry, the content of Cd in tissues increased with time, after 14 days being around 250 and 400 ug/g wet weight in the kidney cortex and liver, respectively. To test the cell endocytosis, rats were injected in vivo with the fluorescein iso-thiocynate-dextran (FITC-dextran, 35 mg/rat, i.v.). Compared to controls, in both liver and kidney PT cells, Cd-intoxicated rats exhibited a much lower uptake of FITC-dextran due to an imhpaired endocytosis. Using the monoclonal anti-tubulin antibody, the immunofluorescence studies showed a bundle-like arrangement of cell microtubules in frozen control tissue sections. In tissues from Cd-treated rats, the arrangement of microtubules was irregular, indicating that the recycling of intracellular vesicles and PM proteins may be impaired in this condition. Indeed, as tested by the specific antibodies, the amount of several brush-border membrane proteins, including the proton-ATPase, carbonic-anhydrase, and dipeptidyl-peptidase IV were drastically reduced in Cd-treated rats. Thus, Cd inhibits cell endocytosis and depletes PM of the important proteins possibly by interfering with the microtubule-dependent intracellular vesicle trafficking. (Tekst na engleskom i hrvtaskom jeziku)

microtubules; kidney; liver; cadmium; nephrotoxicity; rat

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