Proximal tubule cells

Stimulation of basolateral Na /H exchanger transport activity in LLC-PK] cells during chronic metabolic acidosis is accompanied by a parallel increase in NHE-1 transcript abundance [80]. Chronic metabolic acidosis also increases the abundance of Na /H exchanger transcripts in rat renal cortices [81] and SV40-transformed mouse proximal tubule cells [82]. 

Proximal tubule cells are exquisitely sensitive to vasculat disturbances and acute tubular necrosis (ATN) can occur naturally in areas of poor perfusion resulting from falling blood pressure, or vasospasm of renal vessels or arterioles. In other words hypoxia associated with partial ischaemia can cause severe damage. It is not then surprising that anoxia associated with iatrogenic, surgically induced total ischaemia produces irreversible damage within a short time unless steps are taken to prevent it. 

MM Meyer, AS Verkman. Evidence for water channels in renal proximal tubule cell membranes. J Membrane Biol 96 107-119, 1987. 

Sens DA West Virginia University, North Morgantown, WV Validation of cultured human proximal tubule cells as a model for the study of human metal-induced nephropathies National Institute of Environmental Health Sciences... 

Hatzinger, P.B. and Stevens, J.L. (1989). Rat kidney proximal tubule cells in defined medium the roles of cholera toxin, extracellular calcium and serum in cell growth and expression of y-glutamyltransferase. In Vitro Cell. Dev. Biol. 25(2) 205-212. 

Rreisberg, J.I., Pitts, A.M. and Pretlow, T.G. (1977). Separation of proximal tubule cells from suspensions of rat kidney cells in density gradients of Ficoll in tissue culture medium. Am. J. Pathol. 86 591-601. 

Sens, M.A., Hennigar, G.R., Hazen-Martin, D.J. and Sens, D.A. (1988). Cultured human proximal tubule cells as a model for aminoglycoside nephrotoxicity. Ann. Clin. Lab. Set 18 204-214. 

Tay, L.K., Bregman, D.L., Maters, B.G. and Williams, RD. (1988). Effects of A.s-diaminedi-chloroplatinum (I) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture. Cancer Res. 48 2538-2543. 

Yang, I.S., Goldinger, J.M., Flong, S.K. and Taub, M. (1988). Preparation of basolateral membranes that transport p-aminohippurate from primary cultures of rabbit kidney proximal tubule cells. J. Cell. Physicol. 135 481-487. 

Proximal tubule Cells of the PCT are responsible for bulk transport of solutes, with approximately 70-80% of the filtered load of sodium chloride (active processes) and water (passive, down the osmotic gradient established by sodium reabsorption) and essentially all of the amino acids, bicarbonate, glucose and potassium being reabsorbed in this region. 

Several symport proteins have been identified in the luminal and basolateral surfaces of the proximal tubule cells, each with a specific transport function. For example, mechanisms exist for transport of (i) neutral amino acids, except glycine, (ii) glycine alone, (iii) acidic amino acids (glutamate and aspartate), (iv) basic amino acids... 

Gross E, Hawkins K, Pushkin A, Sassani P, Dukkipati R, Abuladze N, Hopfer U, and Kurtz I [2001] Phosphorylation of Ser982 in the sodium bicarbonate cotransporter kNBCl shifts the HCOJ Na+ stoichiometry from 3 1 to 2 1 in murine proximal tubule cells. 1 Physiol 537 659-665... 

B. C. Burckhardt, and G. Burckhardt. Transport of organic anions across the basolateral membrane of proximal tubule cells. Rev Physiol Biochem Pharmacol 146 95-158 (2003). 

Polarising Caco-2 LLC-PK1 MDCK Human colon adenocarcinoma, epithelial, enterocyte-like Porcine kidney, epithelial, proximal tubule cell-like Canine kidney, epithelial, distal tubule cell-like... 

The kidneys are susceptible to toxicity from xenobiotics (Fig. 7.1) because they too have a high blood flow. Cells of the tubular nephron face double-sided exposure, to agents in the blood on the basolateral side and in the Altered urine on the luminal side. Proximal tubule cells are generally the site of nephrotoxicity, since these cells have an abundance of cytochrome P450 and can transport organic anions and cations from the blood into the cells, thereby concentrating these chemicals manyfold. 

Uric acid production is more easily controlled by drug therapy than by dietary restriction, because only a small portion of blood uric acid is derived from the dietary intake of purines. Excretion of uric acid may be increased by increasing the rate of urine flow or by using uricosuric agents. Since uric acid is filtered at the glomerulus and both actively secreted and reabsorbed by the proximal tubule cells, both approaches are effective. 

Lead. Lead, as Pb2+, is taken up readily by proximal tubule cells, where it damages mitochondria and inhibits mitochondrial function, altering the normal absorptive functions of the cell. Complexes of lead with acidic proteins appear as inclusion bodies in the nuclei of tubular epithelium cells. These bodies, formed before signs of lead toxicity occur, appear to serve as a protective mechanism. 

Mercury. Mercury exerts its principle nephrotoxic effect on the membrane of the proximal tubule cell. In low concentrations, mercury binds to the sulfhydryl groups of membrane proteins and acts as a diuretic by inhibiting sodium reabsorption. Organomer-curial diuretics were introduced into clinical practice in the 1920s and were used... 

Uranium. About 50% of plasma uranium is bound, as the uranyl ion, to bicarbonate, which is filtered by the glomerulus. As a result of acidification in the proximal tubule, the bicarbonate complex dissociates, followed by reabsorption of the bicarbonate ion the released UO22"1" then becomes attached to the membrane of the proximal tubule cells. The resultant loss of cell function is evidenced by increased concentrations of glucose, amino acids, and proteins in the urine. 

---