Proximal tubular cells , renal

Ishido, M.S. Homma-Takeda, C. Tohyama, and T. Suzuki. 1998. Apoptosis in rat renal proximal tubular cells induced by cadmium. Jour. Toxicol. Environ. Health 55A 1-12. 

Goligorsky, M.S., Menton, D.M. and Hruska, K.A. (1986). Parathyroid hormone-induced changes of the brush border topography and cytoskeleton in cultured renal proximal tubular cells. J. Membr. Biol. 92 151-162. 

Sakhrani, L.M., Badie-Dezfooly, B., Trizna, W., Mikhails, N., Lowe, A., Taub, M. and Fine, L.G. (1984). Transport and metabolism of glucose by renal proximal tubular cells in primary culture. Amer. J. Physiol. 246 F757-F764. 

Figure 5.10. Accumulation of a radiolabelled LMWP in the lysosomes of the proximal tubular cell. Electron microscope autoradiography of renal proximal tubular cells from a rat injected i.v. with [1251]-tyramine-cellobiose-labelled cytochrome-c, 4 h prior to fixation throngh the abdominal aorta. An intense lysosomal accumulation of the protein is observed in three dark electron-dense lysosomes. A few grains are seen over the apical endocytic apparatus. Part of the luminal brush border is found in the upper right hand corner. Magnification, x 25 000. Unpublished data from E. I. Christensen, Arhus, Denmark, and M. Haas, Groningen, Netherlands.

The above described studies show that the renal proximal tubular cell is a good target for antisense therapy [135],... 

Toxicity is most likely in tissues that interact with the drug. For example, gentamicin is polycationic and binds to anionic phospholipids in the cell membranes of renal proximal tubular cells, where it inhibits phospholipases and damages intracellular organelles. 

L4. Levine, J. S., Koh, J. S., Triaca, V., and Lieberthal, W., Lysophosphatidic acid A novel growth and survival factor for renal proximal tubular cells. Am. J. Physiol. 273, F575—F585 (1997). 

Bhaskaran, M., Reddy, K., Radhakrishnan, N., Franki, N., Ding, G., and Singhal, P.C. 2003. Angiotensin II induces apoptosis in renal proximal tubular cells. Am. J. Physiol. 284 F955-F965. 

In the last few years, many reports have documented ROS-induced activation of the MAPK pathway in different cell types, including Rat-2 fibroblasts (Esposito et al. 2003), rabbit renal proximal tubular cells (Zhuang and Schnellmann 2004), Chinese hamster ovary (CHO) cells (Mehdi et al. 2005), rat cardiomyocytes and heart fibroblasts (Purdom and Chen 2005) as well as VSMCs (Blanc et al. 2003, 2004 Tabet et al. 2005). Moreover, ROS generation was shown to be critical in the activation of MAPK by Ang II (Ushio-Fukai et al. 1998 Touyz et al. 2004) and ET-1 (Daou and Srivastava 2004 Touyz et al. 2004) in VSMCs. 

Jans, A.W.H. Leibfritz, D. (1989). A13C NMR study on fluxes into the Krebs cycle of rabbit renal proximal tubular cells. NMR Biomed. 1,171-176. 

Cytochrome C release may follow the MPT or occur independently. In a recent study of dsplatin toxicity [35] decrease in oxidative phosphorylation was due to the inhibition of mitochondrial FO-Fl-ATPase activity, but the decrease in oxidative phosphorylation was accompanied by hyperpolarization of the mitochondrial membrane rather than a decrease in membrane potential that is usually associated with the MPT [36]. The studies also demonstrate a marked decrease in active Na transport and Na-K-ATPase activity that paralleled the decrease in FO-Fl-ATPase activity and preceded increases in membrane potential in cisplatin treated renal proximal tubular cells. These studies would suggest that cytochrome C release into the cytoplasm and the subsequent formation of the apoptosome (see below) may occur independently of the MPT and that the initiation of cell death by disruption of energy metabolism can directly engage the caspase cascade. 

The development and use of serum free hormonally supplemented medium is, however, a step in the right direction. The apphcation of defined medium allows a more standardized approach to cell culture delivering greater reproducibility and transferability. For renal tubular cells, defined medium supplements have been described as far back as 1982 [64], and we have successfully cultured human renal proximal tubular cells in defined medium containing EGF, hydrocortisone, insulin, transferrin and sodium selenite using DMEM-Hams F12 as the base medium [42]. 

Potential direct nephrotoxicity and the underlying molecular mechanisms were analyzed by in vitro studies in renal proximal tubular cells exposed to IFNa. IFNa was shown to induce apoptosis in LLC-PKl renal proximal tubular like epithelium [216]. Caspase-8, a key player in death receptor signaling and caspase-9 that is involved in mitochondrial apoptosis were shown to be activated in addition to caspase-3. Furthermore, IFNa induced a breakdown of the inner mitochondrial membrane potential, further implying mitochondrial signahng in IFNa-induced apoptosis. The deafh receptor pathway and the mitochondrial pathway appear to both be necessary for efficient executor caspase activation by IFNa. The apoptotic signaling pathways activated by IFNa in proximal tubular cells, thus, resemble the pathways induced by IFNa in melanoma and bladder carcinoma cells [217, 218]. In addition to caspase activation, nuclear condensation, DNA fragmentation and a delayed LDH release were observed. DNA fragmentation and LDH release were partially prevented by caspase inhibition. Thus, caspase-inde-pendent death is also possible - albeit delayed and at a reduced extent [216]. 

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. 

Joly V, Saint-Julien L, Carbon C, Yeni P. Interactions of free and liposomal amphotericin B with renal proximal tubular cells in primary culture. J Pharmacol ExpTher 1990 255 17-22. 

Tervahartiala P, Kivisaari L, Kivisaari R, VehmasT, Virtanen I. Structural changes in the renal proximal tubular cells induced by iodinated contrast media. Nephron 1997 76 96-102. 

Organic mercurials are capable of inducing nephrotoxicity in S2 and S3 segments of the proximal tubule. Part of the S3 damage results from the biotransformation of the organic mercurial to release mercuric ions. Methylmercury (CH3Hg + ) readily concentrates in renal proximal tubular cells and alters mitochondrial function and lysosomes. At least part of methylmercury-induced nephrotoxicity may be due to homolytic scission of methylmercury to release methyl radicals and to lipid peroxidative toxicity. 

The first member of this carrier family, Oatplal, has been cloned from rat liver [8]. Oatplal is an 80 kDa protein that is expressed at the basolateral membrane of hepatocytes as well as at the apical membranes ofthe renal proximal tubular cells and choroid plexus epithelial cells [11-14]. 

Sheikh, S.P., Sheikh, M.I. Schwartz, T.W. (1989) Y2-type receptors for peptide YY on renal proximal tubular cells in the rabbit. Am.J. Physiol. 257, F978-F984. 

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