TY - JOUR A1 - Singh, Jasbir A1 - Dani, Harinder M. A1 - Sharma, Reeta A1 - Steinberg, Pablo T1 - Inhibition of the biosynthesis of SRP polypeptides and secretory proteins by aflatoxin B-1 can disrupt protein targeting JF - Cell biochemistry and function N2 - Cell culture and western blotting studies revealed that aflatoxin B-1 (AFB(1)) inhibits the biosynthesis of two of the constituent polypeptides of signal recognition particle (SRP) (SRP54 and 72). SRP escorts polyribosomes carrying signal peptides from free form in the cytosol to the bound form on endoplasmic reticulum (ER) membrane during protein targeting. These effects of AFB(1) on SRP biosynthesis may inhibit the formation of functional SRP Our experiments have further shown that AFB(1) also inhibits the biosynthesis/translocation of a secretory protein, preprolactin, which fails to appear in the lumen of ER consequent to the treatment with this hepatocarcinogen. The results of the experiments presented in this article therefore enable us to infer for the first time that aflatoxin B-1 may inhibit the functioning of SRP as an escort and deplete the ER of polyribosomes for secretory protein synthesis. As these secretory proteins are important components of the plasma membrane, gap junctions and intercellular matrix, their absence from these locations could disturb cell to cell communication leading to tumorigenesis. KW - aflatoxin B-1 KW - SRP KW - protein targeting KW - protein translocation KW - western blotting Y1 - 2005 U6 - https://doi.org/10.1027/cbf.1285 SN - 0263-6484 VL - 24 SP - 507 EP - 510 PB - Wiley CY - Chichester ER - TY - JOUR A1 - Singh, Jasbir A1 - Singh, S. A1 - Dani, H. M. A1 - Sharma, Reeta A1 - Steinberg, Pablo T1 - Interactions of aflatoxin B-1 with SRP components can disrupt protein targeting N2 - Spectrofluorimetric studies have revealed that aflatoxin B-1 (AFB(1)) interacts with signal recognition particle (SRP), which acts as an escort for polyribosomes with signal peptides to be transported and bound to the cytoplasmic face of the endoplasmic reticulum (ER). We further report that the binding of AFB(1) to SRP is selective as it only binds to two (SRP9 and 14) out of its three constituent polypeptides studied. Binding of AFB(1) to proteins is known to alter their conformations. Interactions of AFB(1) with SRP polypeptides may generate structural and functional alterations in this particle and hinder secretory protein synthesis. Copyright (C) 2004 John Wiley Sons, Ltd Y1 - 2005 SN - 0263-6484 ER - TY - JOUR A1 - Fuchs, J. A1 - Teubner, Wera A1 - Steinberg, Pablo T1 - The resistance of intestinal epithelial cells towards the transforming activity of 2-hydroxyamino-1-methyl-6- phenylimidazo[4,5-B]pyridine is accompanied by glutathione S-transferase induction Y1 - 2004 SN - 0028-1298 ER - TY - JOUR A1 - Teubner, Wera A1 - Langheinrich, C. A1 - Seidel, Albrecht A1 - Steinberg, Pablo T1 - Inhibition of p53 transactivation activity does not promote mutagen-induced transformation of IEC-18 Y1 - 2004 SN - 0028-1298 ER - TY - JOUR A1 - Stark, Avishay abraham A1 - Porat, Noga A1 - Volohonsky, Gloria A1 - Konlosh, A. A1 - Bluvshtein, Evgenia A1 - Tubi, C. A1 - Steinberg, Pablo T1 - The role of gamma-glutamyl transpeptidase in the biosynthesis of glutathione Y1 - 2003 ER - TY - JOUR A1 - Okano, J. A1 - Shiota, G. A1 - Matsumoto, K. A1 - Yasui, S. A1 - Kurimasa, A. A1 - Hisatome, I. A1 - Steinberg, Pablo A1 - Murawaki, Y. T1 - Hepatocyte growth factor exerts a proliferative effect on oval cells through the PI3K/AKT signaling pathway Y1 - 2003 ER - TY - JOUR A1 - Bartsch, Ingrid A1 - Zschaler, Ingrid A1 - Haseloff, Monika A1 - Steinberg, Pablo T1 - Establishment of a long-term culture system for rat colon epithelial cells N2 - The aim of this study was to establish a long-term culture. system for rat colon epithelia isolaled by incubating a 4-cm-long rat colon segment cut longitudinally with all ethylenediaminetetraacetic acid [disodium salt]- containing buffer, taken up in conditioned medium from the normal rat kidney fibroblast cell line NRK (i.e., the supernatant Of pure NRK cultures), directly plated on mitomycin C-treated NRK cells and subcultured with conditioned medium from NRK cells. Cells started to migrate out of the crypts shortly after plating them on NRK feeder layers. Some of the crypts fell apart during the isolation procedure. whereas the vast majority of them did it within I to 2 Ill after plating. The cells proliferated extremely slowly but continuously over a period of 4 mo and were epithelial because they expressed cytokeratin 19 and were stained by crystal violet at pH 2.8. In conclusion, the experimental system described ill this study allows to maintain rat colon epithelial cells for up to 4 mo in culture and can be used to Study the effects of a variety of tumor-modulating factors on growth and gene expression of normal colon epithelial cells in vitro Y1 - 2003 UR - http://www.springerlink.com/content/120498/ U6 - https://doi.org/10.1290/0404035.1 SN - 1071-2690 ER - TY - JOUR A1 - Barlow, S. M. A1 - Greig, J. B. A1 - Bridges, J. W. A1 - Carere, A. A1 - Carpy, A. J. A1 - Galli, Corrado L. A1 - Kleiner, J. A1 - Knudsen, I. A1 - Koeter, H. B. A1 - Levy, L. S. A1 - Madsen, C. A1 - Mayer, S. A1 - Narbonne, J. F. A1 - Pfannkuch, F. A1 - Prodanchuk, M. G. A1 - Smith, Mason R. A1 - Steinberg, Pablo T1 - Hazard identification by methods of animal-based toxicology Y1 - 2002 ER - TY - JOUR A1 - Dybing, E. A1 - Doe, J. A1 - Groten, J. A1 - Kleiner, J. A1 - O'Brien, J. A1 - Renwick, A. G. A1 - Schlatter, J. A1 - Steinberg, Pablo A1 - Tritschler, A. A1 - Walker, R. A1 - Younes, M. T1 - Hazard characterisation of chemicals in food and diet : dose response, mechanisms and extrapolation issues Y1 - 2002 ER - TY - JOUR A1 - Volohonsky, Gloria A1 - Tuby, Chen N. Y. H. A1 - Porat, Noga A1 - Wellman-Rousseau, Maria A1 - Visvikis, Athanase A1 - Leroy, Pierre A1 - Rashi, Sharon A1 - Steinberg, Pablo A1 - Stark, Avishay Abraham T1 - A spectrophotometric assay of gamma-glutamylcysteine synthetase and glutathione synthetase in crude extracts from tissues and cultured mammalian cells Y1 - 2002 ER -