Proximal tubular lining cells

Colon adenocarcinoma epithelial cell line Rat renal proximal tubular epithelial cell line Tetrahydrofuranyl Valacyclovir hydrolase... 

Romero MF, Douglas JG, Eckert RL, Elopfer L), Jacobberger JW. Development and characterization of rabbit proximal tubular epithelial cell lines. Kidney Int 1992 42 1130-1144. 

The proximal tubular cell plays a major role in the elimination of both inorganic and organic substrates. The ceUs have two distinct membrane domains. The basolateral membrane is in contact with the blood, and the apical brush-border membrane lines the tubular lumen. 

Romiti N, Tramonti G, Donati A, Chieli E. Effects of grapefruit juice on the multidrug transporter P-glycoprotein in the human proximal tubular cell line HK-2. Life Sci 2004 76(3) 293-302. 

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]. 

Nanomolar concentrations of OTA resulted in the stable and irreversible dedifferentiation of MDCK-C7 cells, characterized by a distinct morphology as compared to the parent cell line (spindle-shape, pleiomor-phic, narrow intercellular spaces, increased cell size), a reduced proliferation rate and numerical chromosomal aberrations [202]. Further studies could demonstrate that OTA exposure resulted in apoptosis, which was associated with induced c-jun amino-terminal-kinase (JNK) activation [203]. Long term exposure (14 days) of human proximal tubular cells to nanomolar concentrations of OTA under serum free conditions led to cell hypertrophy, NF-kappaB activation, fibronectin secre-... 

Flealy E, Dempsey M, Lally C, and Ryan MP. Apoptosis and necrosis mechanisms of cell death induced by cyclosporine A in a renal proximal tubular cell line. Kidney Int 54 1955-1966,1998. 

Flahn FI, FluckCW, Rainer M, Najam-ul-Flaq M, Bakry R, AbbergerT, Jennings P, Pfaller W, and Bonn GK. Analysis of glutathione in supernatants and lysates of a human proximal tubular cell line from perfusion culture upon intoxication with cadmium chloride by HPLC and LC-ESI-MS. Anal Bioanal Chem 388 1763-1769,2007. 

In the Wistar rat model, the daily administration of 10 mg per kg body weight of AA induced, after 35 days, renal failure wifh interstitial fibrosis (Figure 2) as well as a papillary urothehal cardnoma of the pelvis in some animals [63,64]. Nephrotoxidty of different components of AA was also studied in three strains of inbred male mice. The C3H/He mice intraperitoneaUy injected with 2.5 mg/Kg of AA, five days a week, for 2 weeks, developed on day 14 foci of proximal tubule injury surrounded by mononuclear cell infiltration. Two weeks later, signs of proximal tubule cell prohf-eration were observed whereas the inflammatory ceUs infiltration became more severe and interstitial fibrosis occurred [65]. In this mice model, AAI exhibited a higher nephrotoxidty than AAII [65], which was also confirmed in in vitro studies on proximal tubular LLC-PKl ceUs line [66]. 

There have been several investigations into the use of hormonally defined medium in order to maintain the differentiation of primary cells, as it is suspected that serum may be a factor in dedifferentiation. The application of defined medium also allows a more standardized approach to cell culture delivering greater reproducibility and transferability. For renal tubular epithelial cells defined medium supplements have been described as far back as 1982 [148], We have been, over the last number of years, successfully cultivating human renal proximal tubular cells (primaries and cell lines) in serum free hormonally defined medium containing EGF, hydrocortisone, insulin, transferrin, and sodium selenite using DMEM-Hams F12 as the base medium [36, 112, 114, 149], Both the HK-2 cell line and the RPTEC/TERT1 have been developed in serum-free conditions. 

Rabito CA (1986) Occluding junctions in a renal cell line (LLC-PK1) with characteristics of proximal tubular cells. Am J Physiol 250(4 Pt 2) F734-F743... 

Ether-extracted freeze-dried kidney tissue contained the o-quinone metabolite of NDGA, seen as red-brown granules. It was also seen as yellowbrown material in histiocytes, degenerating proximal tubular epithelium, small acellular casts, and occasionally in the cells lining the cysts and in the lumen of the proximal convoluted tubules. No free NDGA was found in the rat kidneys (Goodman et al., 1970). 

CSA has also been shown to cause toxico-tolerance in vitro. CsA, which is transported via the P-glycopro-tein, increases the expression of P-glycoprotein in rat proximal tubular cells [183] and in the human proximal tubular cell line HK-2 [183a]. CSA also induces the expression of HSP 70 in LLC-PKj cells, which increases tolerance to subsequent exposure to CSA [184]. 

Further evidence to support a direct toxic effect of AmB on renal cells is the demonstration of increased apoptosis in proximal tubular and medullary interstitial cell lines [65]. The occurrence of apoptosis has also been confirmed in an in-vivo model in rats in which AmB administration also caused hypokalemia, loss of concentrating ability and dehydration. Interestingly, prevention of apoptosis by recombinant human insulin growth factor-1 (rhIGF-1) ameliorated the tubular toxidly indicating the importance of apoptosis in AmB-induced renal tubular toxicity process. A possible mechanism for this action is suggested by a recent study that has demonstrated that AmB exposure increases cellular ceramide as well as sphingomyelin levels in proximal tubular cells [66]. It is noteworthy that... 

Induction of oollagen secretion (a marker of fibrosis) has been shown in the OK proximal tubular cell line and in cultured primary human renal proximal tubular oells exposed to ochratoxin A. Collagen seoretion was both time and dose dependent, as was the induction of cell toxicity (Sauvant et al., 2005a). 

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