Hepatomas Receptors

Using human hepatoma-derived cell lines Kong et al. [268] showed that berberine increased mRNA and protein as well as the function of hepatic linear low density lipoprotein receptor (LDLR). It does not stimulate the transcription of LDLR, as the LDLR promoter activity was not increased by this compound. Post-transcriptional regulation appears to be the main working mechanism underlying the effect of this alkaloid on LDLR expression. It was proposed that berberine can be used as a monotherapy to treat hypercholes-terolemic patients [268]. Very recently it was observed [269] that berberine reduces cholesterol and Upid accumulations in plasma as well as Uver. 

Another potential source of iron, at least for hepatocytes, is receptor-independent uptake of iron from transferrin. This appears to involve an iron uptake pathway from transferrin which is neither suppressed in hepatocytes by antibodies to TfR (Trinder et at, 1988), nor by transfection of HuH-7 hepatoma cells with transferrin receptor anti-sense cDNA (Trinder etat, 1996). The same pathway may also be utilized for iron uptake from isolated transferrin N-lobe, which is not recognized by the receptor (Thorstensen et at, 1995). The possible role of TfR2 in this process remains to be established, as does the physiological importance of this pathway in intact liver. Human melanoma cells (Richardson and Baker, 1994) and Chinese hamster cells lacking transferrin receptors but transfected with melanotransferrin (Kennard et at, 1995) use another pathway for transferrin iron uptake, independent of the transferrin receptor, but utilizing iron transfer from transferrin or simple iron chelates to membrane-anchored melanotransferrin, and from there onwards into the cellular interior. 

Tributyltins and other organotins induce chromosomal aberrations in mammals, although this was not observed in tests with aquatic invertebrates (Dixon and Prosser 1986). Studies with isolated rat hepatoma cells, TBT, and PCB 126, show that TBT inhibits cytochrome P-4501A activity, and PCB 126 induces EROD activity. However, PCB-induced EROD activity was potentiated by coexposure to low noncytotoxic concentrations of TBT (Kannan et al. 1998b). Authors concluded that TBT does not interfere with Ah receptor binding and that potentiation of EROD activity and cytotoxicity as a result of coexposure to PCB 126 and TBT is significant because they coaccumulated in a variety of marine organisms. 

Villeneuve, D.L. Crunkilton, R.L. DeVita, W.M. 1997, Aryl hydrocarbon receptor-mediated toxic potency of dissolved lipophilic organic contaminants collected from Lincoln Creek, Milwaukee, Wisconsin, USA, to PLHC-1 (Poeciliopsis lucida) fish hepatoma cells. Environ. Toxicol. Chem. 16 977-984. 

Numerous studies have demonstrated the protective effect of exogenously apphed SIP. In many cases, the protective effects of SIP have been associated with the activation of signaling pathways mediated via EDG receptors (Figure 3). For example, S IP-dependent inhibition of serum-withdrawal-induced apoptosis of HTC4 hepatoma cells was mediated by transfected EDG3 or EDG5. S IP-induced protection involved EDG receptor-dependent activation of p42/p44 MAPK, inhibition of caspase-3... 

Meretey K, Falus A. Taga T. Kishimoto T Histamine influences the expression of the interleukin-6 receptor on human lymphoid, monocytoid and hepatoma ceU hnes. Agents Actions 1991 33 189-191. 

Junbo, H., Q. Li, W. Zaide, and H. Yunde, Receptor-mediated interleukin-2 gene transfer into human hepatoma cells. Int J Mol Med, 1999. 3(6) 601-8. 

Saad, M.J.A. Folli, R Kahn, C.R. Insulin and dexamethasone regulate insulin receptors, insulin receptor substrate-1, and phosphatidylinositol 3-kinase in Fao hepatoma cells. Endocrinology, 136, 1579-1588 (1995)... 

Oishi et al. coupled lactosylated PEG to siRNA via an acid labile (S-thiopropio-nate bond, followed by complexation with poly(L-lysine) into polyion complex micelles. The complex was internalized by receptor-mediated endocytosis into hepatoma cells and the gene silencing effect of RNAi was considerably enhanced compared to the free conjugate, demonstrating the effect of pH-sensitive PEGylation [56]. 

Ciechanover, A., Schwartz, A. L., Dautry-Varsat, A., and Lodish, H. F. Kinetics of internalization and recycling of transferrin and the transferrin receptor in a human hepatoma cell line. Effect of lysosomotropic agents. J. Biol. Chem. 258 9681-969, 1983. 

The receptor density is also decreased in patients with primary or secondary liver cancer. The extent of this decrease expresses the nonfunctioning liver mass, because metastasis or hepatoma does not show uptake of 99raTc-NGA in vivo... 

Many putative receptors for anti-dsDNA on the membrane of various cell types have been noted. Some workers found a 30-kDa protein involved in the binding and internalization of [3H]DNA via receptor-mediated endocytosis (B12, B13). Other possible receptors include nucleosomes on human leukocytes (R8), Fc receptors on human T cells (A6), DNA on mouse and human mononuclear cells (06), a 94-kDa protein on several cells lines (J2), DNase-resistant target on human fibroblasts and PK 15 cells (K9), membrane determinant precisely resembling DNA in murine renal tubular cells (Zl), Hp8 on human and murine tubular cells (Z2), ribosomal P protein on rat and human glomerular mesangial cells (S30, S31), brush border myosin 110 kDa on rat hepatoma cells, and a diverse set of membrane proteins on a series of human tumor cell lines (R3). 

TCDD suppression of B lymphocyte differentiation by competing for binding to the Ah receptor. The mechanism of interaction of these chemicals was studied in vitro using rat hepatic cytosol or mouse hepatoma cells (Gasiewicz and Rucci 1991). The results indicated that -naphthoflavone acts as a... 

Perdew GH. 1992. Chemical cross-linking of the cytosolic and nuclear form of the Ah receptor in hepatoma cell line lclc7. Biochem Biophys Res Comm 182 55-62. 

Weib C, Kolluri SK, Kiefer F, et al. 1996. Complementation of Ah receptor deficiency in hepatoma cells negative feedback regulation and cell cycle control by the Ah receptor. Exp Cell Res 226 154-163. 

Prokipcak RD, Okey AB. Downregulation of the Ah receptor in mouse hepatoma cells treated in culture with 2,3,7,8-tetrachlorodibenzo-p-dioxin. Can J Physiol Pharmacol 1991 69 1204—1210. 

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