Renal cell lines

Finn GJ, Kenealy E, Creaven BS, Egan DA (2002) In vitro cytotoxic potential and mechanism of action of selected coumarins, using human renal cell lines. Cancer Lett 183 61-68... 

Renal Cells. A variety of isolated cellular models exist for studying renal function and injury. These models can generally be divided into two categories models derived from permanent renal cell lines and cellular models derived from freshly isolated renal tissue. 

Cell Lines. Cell lines, derived from tissue of various species, are commercially available from tissue culture banks. These cell populations are immortalized in that they possess the capacity to permanently proliferate in culture. Such cellular models can be studied in short-term suspension (hours) or longer-term monolayer culture (days, weeks, months). Since cell lines have been extensively cultured or passaged for multiple generations, the degree or retention (or loss) of kidney-specific morphology and function is an important limitation that is not thoroughly addressed for a number of renal cell lines. One renal cell line that has been relatively well characterized is the pig kidney cell line, LLC-PK,. 

Renal cell lines have been utilized to a limited extent for evaluation nephrotoxins. A rabbit kidney cell line (LLC-RKi) has been utilized for evaluating nephrotoxic antibiotics (Viano et al., 1983 Hottendorf et al., 1987 Williams et al., 1988). LLC-PKi cells have by far been the most widely employed cell line for studying drug-induced nephrotoxicity, specifically in the evaluation of aminoglycoside antibiotics (Hori et al., 1984 Schwertz et al., 1986 Williams et al., 1986b Holohan et al.,... 

Rabito, C.A. (1986). Occluding junctions in a renal cell line (LLC-PKQ. The basolateral systems. J. Biol. Chem. 257 6802-6808. 

Whether these requirements are better met by primary cultures or renal cell lines is still subject of debate and will depend on the type of investigation. Techniques for the isolation and culture of primary cells of the renal tubular epithelium, glomerular mesangial cells, podocytes and endothelial cells have been developed for various species including human. Although cells in primary culture tend to dedifferentiate, the characteristics of those cells are usually closer to the in vivo situation than are animal cell tines, at least for a limited culture period. Primary cultures have been used successfully to study the in vitro effects of numerous nephrotoxins including, cyclosporine A (CsA), gentamicin, mercuric chloride and Ochratoxin A [38-42]. 

In a study of six mercury compounds, mercury chloride, mercury nitrate, sodium ethylmercurithi-osalicylate, methyl mercury chloride, mercury acetate and phenylmercury acetate in MDCK cells, LLC-PKl cells and human primary proximal tubular cells (hPTC) and non-renal cell lines (SAOS and Hep G2) it was found that all mercury compounds were toxic to all cell types as evidenced by neutral red uptake, thymidine incorporation and the MTT assay [189]. However, sodium ethylmercurithiosalicylate, methyl mercury chloride and phenylmercury acetate were one order of magnitude more toxic than the other compounds. In addition the GSH synthesis inhibitor L-buthionine sulfoximine (BSO) potentiated the toxicity of all mercury compounds [189]. In a study using primary rabbit proximal tubular cells it was also shown that methyl mercury chloride is more toxic than mercury chloride [190]. Differences in the extent and rate of metal uptake were also evident. Maximum cellular uptake of Hg " occurred within 6-24 hr after exposure and was not concentration-dependent, whereas maximum uptake of CHgHg" occurred within 3 hr of exposure and was concentration- dependent [190]. 

Gstraunthaler G and Pfaller W. Continuous renal cell lines as in vitro tools to study nephrotoxicity, in vitro Methods ofToxIcology 93-113,1992. 

Simmons NL. Tissue culture of established renal cell lines. Methods Enzymol 191 426-436,1990. 

Holcomb T, Curthoys NP, and Gstraunthaler G. Subcellular localization of PEPCKand metabolism of gluconeogenic substrains of renal cell lines. Am J Physiol 268 C449-457,1995. 

Nakahama H, Fukunaga M, Kakihara M, Horio M, Fujiwara Y, Fukuhara Y, Ueda N, Orita Y, and Kamada T. Comparative effects of cyclosporine A and FK-506 on endothelin secretion by a cultured renal cell line, LLC-PKI. J Cardiovasc Pharmacol 17 SuppI 7 5172-173,1991. 

El Mouedden M, Laurent G, Mingeot-Eeclercq MP, and Tulkens PM. Gentamicin-induced apoptosis in renal cell lines and embryonic rat fibroblasts.Toxicol Sci 56 229-239,2000. 

Duncan-Achanzar KB, Jones JT, Burke ME, Carter DE, and Eaird ElEn. Inorganic mercury chloride-induced apoptosis in the cultured porcine renal cell line EEC-PK1. J Pharmacol Exp Ther 277 1726-1732,1996. 

Whether these requirements are better met by primary cultures or renal cell lines is stiU subject of de-... 

By utilizing horseradish-peroxidase-labeled OTA in western blots Schwerdt et al. [238] could show that in different renal cell lines (MEXTK-Cll, OK, LLC-PKj and immortalized human kidney epithelial cells (IHKE)) OTA binds directly to certain proteins. Thus OTA-protein binding damages normal protein function. Moreover, such binding results in a further accumulation of OTA [237]. 

Wohlwend A, Vassalli JD, Bertrand D, Orci L. Calcitonin and vasopressin affect epithelial properties in a renal cell line. J Cell Physiol 1986 128 71-75. 

Arend U, Elandler JS, Thim JS, Gusovsky F, Spielman WS. Aadenosine-sensitive phospho-inositide turnover in a newly established renal cell line. Am J physiol 1989 256 F1067-F1074. 

Charlton JA, Simmons NL. Established human renal cell lines pnenotypic characteristics define suitability for use in in vitro models for predictive toxicology. Toxic In vitro 1993 7 129-136. 

Vlasveld [50] obtained biopsy material from a patient with renal cell cancer who developed acute renal failure in the sixth week of a continuous rIL-2 infusion. The pathology was that of acute tubulo-intersti-tial nephritis. Further studies on cryopreserved peripheral blcxxi lymphocytes revealed specific cytolytic activity against an autologous renal cell line cultured from the biopsy specimen. These findings are consistent with an allergic reaction to IL-2. 

For instance, cardenolide glycosides, such as 2 -acetylneriifolin, exhibited a specific pattern of cytotoxic activity in the NCI panel of cell lines (54). Certain cell lines, particularly those among the non-small-cell lung, brain tumor, and renal-cell lines are exceptionally sensitive to 2 -acetylneriifolin, whereas most of the leukemia and colon cell lines were less sensitive to it. From the similar pattern of activity produced by crude extracts of plants of the classes Apocyanaceae and Asclepiadaceae, NCI scientists concluded in this study that similar cardenolide glycosides are present in these extracts. 

The renal cell lines, JTC-12 and MDCK, not only synthesize D-galactosyl-ceramide 3-sulphate and lactosyl 3-sulphate in vivo, but competition studies indicate that both ceramides became sulphated by a single enzyme in both cell lines. 

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