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 - TY - JOUR A1 - Thierbach, René A1 - Drewes, Gunnar A1 - Fusser, Markus A1 - Wolfrum, Kathrin A1 - Epe, Bernd A1 - Ristow, Michael A1 - Steinberg, Pablo T1 - A role for iron-sulfur cluster proteins in DNA repair Y1 - 2009 UR - http://www.springerlink.com/content/100530 U6 - https://doi.org/10.1007/s00210-009-0404-1 SN - 0028-1298 ER - TY - JOUR A1 - Thierbach, René A1 - Drewes, Gunnar A1 - Fusser, Markus A1 - Voigt, Anja A1 - Kuhlow, Doreen A1 - Blume, Urte A1 - Schulz, Tim Julius A1 - Reiche, Carina A1 - Glatt, Hansruedi A1 - Epe, Bernd A1 - Steinberg, Pablo A1 - Ristow, Michael T1 - The Friedreich's ataxia protein frataxin modulates DNA base excision repair in prokaryotes and mammals N2 - DNA-repair mechanisms enable cells to maintain their genetic information by protecting it from mutations that may cause malignant growth. Recent evidence suggests that specific DNA-repair enzymes contain ISCs (iron-sulfur clusters). The nuclear-encoded protein frataxin is essential for the mitochondrial biosynthesis of ISCs. Frataxin deficiency causes a neurodegenerative disorder named Friedreich's ataxia in humans. Various types of cancer occurring at young age are associated with this disease, and hence with frataxin deficiency. Mice carrying a hepatocyte- specific disruption of the frataxin gene develop multiple liver tumours for unresolved reasons. In the present study, we show that frataxin deficiency in murine liver is associated with increased basal levels of oxidative DNA base damage. Accordingly, eukaryotic V79 fibroblasts overexpressing human frataxin show decreased basal levels of these modifications, while prokaryotic Salmonella enterica serotype Typhimurium TA 104 strains transformed with human frataxin show decreased mutation rates. The repair rates of oxidative DNA base modifications in V79 cells overexpressing frataxin were significantly higher than in control cells. Lastly, cleavage activity related to the ISC-independent repair enzyme 8-oxoguanine glycosylase was found to be unaltered by frataxin overexpression. These findings indicate that frataxin modulates DNA-repair mechanisms probably due to its impact on ISC-dependent repair proteins, linking mitochondrial dysfunction to DNA repair and tumour initiation. Y1 - 2010 UR - http://www.biochemj.org/bj/toc.htm U6 - https://doi.org/10.1042/Bj20101116 SN - 0264-6021 ER - TY - JOUR A1 - Thierbach, René A1 - Blume, Urte A1 - Wolfrum, K. A1 - Drewes, Gunnar A1 - Voigt, Anja A1 - Ristow, Michael A1 - Steinberg, Pablo T1 - Altered carbohydrate metabolism in a tumour developing knock-out mice model Y1 - 2010 UR - http://www.springerlink.com/content/100530 U6 - https://doi.org/10.1007/s00210-010-0508-7 SN - 0028-1298 ER - TY - JOUR A1 - Thierbach, Renè A1 - Schulz, Tim Julius A1 - Isken, Frank A1 - Voigt, Aanja A1 - Mietzner, Brun A1 - Drewes, Gunnar A1 - von Kleist-Retzow, Jürgen-Christoph A1 - Wiesner, Rudolf J. A1 - Magnuson, Mark A. A1 - Puccio, Helene A1 - Pfeiffer, Andreas F. H. A1 - Steinberg, Pablo A1 - Ristow, Michael T1 - Targeted disruption of hepatic frataxin expression causes impaired mitochondrial function, decreased life span and tumor growth in mice N2 - We have disrupted expression of the mitochondrial Friedreich ataxia protein frataxin specifically in murine hepatocytes to generate mice with impaired mitochondrial function and decreased oxidative phosphorylation. These animals have a reduced life span and develop multiple hepatic tumors. Livers also show increased oxidative stress, impaired respiration and reduced ATP levels paralleled by reduced activity of iron-sulfur cluster (Fe/S) containing proteins (ISP), which all leads to increased hepatocyte turnover by promoting both apoptosis and proliferation. Accordingly, phosphorylation of the stress-inducible p38 MAP kinase was found to be specifically impaired following disruption of frataxin. Taken together, these findings indicate that frataxin may act as a mitochondrial tumor suppressor protein in mammals Y1 - 2005 ER - TY - JOUR A1 - Thierbach, Rene A1 - Schulz, Tim Julius A1 - Voigt, Aanja A1 - Drewes, Gunnar A1 - Isken, F. A1 - Pfeiffer, Andreas F. H. A1 - Ristow, Michael A1 - Steinberg, Pablo T1 - Targeted disruption of frataxin in hepatocytes causes spontaneous neoplasia accompanied by increased ROS formation Y1 - 2004 SN - 0028-1298 ER - TY - JOUR A1 - Thierbach, Rene A1 - Florian, Simone A1 - Wolfrum, Katharina A1 - Voigt, Anja A1 - Drewes, Gunnar A1 - Blume, Urte A1 - Bannasch, Peter A1 - Ristow, Michael A1 - Steinberg, Pablo T1 - Specific alterations of carbohydrate metabolism are associated with hepatocarcinogenesis in mitochondrially impaired mice JF - Human molecular genetics N2 - Friedreich's ataxia is an inherited neurodegenerative disease caused by the reduced expression of the mitochondrially active protein frataxin. We have previously shown that mice with a hepatocyte-specific frataxin knockout (AlbFxn(-/-)) develop multiple hepatic tumors in later life. In the present study, hepatic carbohydrate metabolism in AlbFxn(-/-) mice at an early and late life stage was analyzed. In young (5-week-old) AlbFxn(-/-) mice hepatic ATP, glucose-6-phosphate and glycogen levels were found to be reduced by similar to 74, 80 and 88%, respectively, when compared with control animals. This pronounced ATP, G6P and glycogen depletion in the livers of young mice reverted in older animals: while half of the mice die before 30 weeks of age, the other half reaches 17 months of age and exhibits glycogen, G6P and ATP levels similar to those in age-matched controls. A key event in this respect seems to be the up-regulation of GLUT1, the predominant glucose transporter in fetal liver parenchyma, which became evident in AlbFxn(-/-) mice being 5-12 weeks of age. The most significant histological findings in animals being 17 or 22 months of age were the appearance of multiple clear cell, mixed cell and basophilic foci throughout the liver parenchyma as well as the development of hepatocellular adenomas and carcinomas. The hepatocarcinogenic process in AlbFxn 2/2 mice shows remarkable differences regarding carbohydrate metabolism alterations when compared with all other chemically and virally driven liver cancer models described up to now. Y1 - 2012 U6 - https://doi.org/10.1093/hmg/ddr499 SN - 0964-6906 VL - 21 IS - 3 SP - 656 EP - 663 PB - Oxford Univ. Press CY - Oxford 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 - Steinberg, Pablo A1 - Zschaler, Ingrid A1 - Thom, Elke A1 - Kuna, Manuela A1 - Wüst, Günter A1 - Schäfer-Schwebel, Angelika A1 - Müller, Rolf A1 - Kramer, Peter-Jürgen A1 - Weiße, Günter T1 - The polycyclic musk 7-acetyl-1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthaline lacks liver tumor initiating and promoting activity in rats exposed to human-relevant doses Y1 - 2001 UR - http://www.springerlink.com/content/100462 U6 - https://doi.org/10.1007/s002040100274 SN - 0340-5761 ER - TY - JOUR A1 - Steinberg, Pablo A1 - Klingelhöffer, Alexandra A1 - Schäfer, Angelika A1 - Wüst, Günter A1 - Weiße, Günter A1 - Oesch, Franz A1 - Eigenbrodt, Erich T1 - Expression of pyruvate kinase M2 in preneoplastic hepatic foci of N-nitrosomorpholine-treated rats Y1 - 1999 ER -