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Relationship between hepatic phenotype and changes in gene expression in cytochrome P450 reductase (POR) null mice

2005 Biochemical Journal  
Cytochrome P450 reductase is the unique electron donor for microsomal cytochrome P450s; these enzymes play a major role in the metabolism of endogenous and xenobiotic compounds. In mice with a liver-specific deletion of cytochrome P450 reductase, hepatic cytochrome P450 activity is ablated, with consequent changes in bile acid and lipid homoeostasis. In order to gain insights into the metabolic changes resulting from this phenotype, we have analysed changes in hepatic mRNA expression using
more » ... array analysis and real-time PCR. In parallel with the perturbations in bile acid levels, changes in the expression of key enzymes involved in cholesterol and lipid homoeostasis were observed in hepatic cytochrome P450 reductase null mice. This was characterized by a reduced expression of Cyp7b1, and elevation of Cyp7a1 and Cyp8b1 expression. The levels of mRNAs for other cytochrome P450 genes, including Cyp2b10, Cyp2c29, Cyp3a11 and Cyp3a16, were increased, demonstrating that endo-genous factors play a role in regulating the expression of these proteins and that the increases are due, at least in part, to altered levels of transcripts. In addition, levels of mRNAs encoding genes involved in glycolysis and lipid transport were also increased; the latter may provide an explanation for the increased hepatic lipid content observed in the hepatic null mice. Serum testosterone and oestradiol levels were lowered, accompanied by significantly decreased expression of Hsd3b2 (3β-hydroxy-5 -steroid dehydrogenase-2), Hsd3b5 (3β-hydroxy-5 -steroid dehydrogenase-5) and Hsd11b1 (11β-hydroxysteroid dehydrogenase type 1), key enzymes in steroid hormone metabolism. These microarray data provide important insights into the control of metabolic pathways by the cytochrome system.
doi:10.1042/bj20042087 pmid:15717863 pmcid:PMC1183466 fatcat:gs6zqobeqzbvhkwjudynlttxu4

The RAST Server: Rapid Annotations using Subsystems Technology

Ramy K Aziz, Daniela Bartels, Aaron A Best, Matthew DeJongh, Terrence Disz, Robert A Edwards, Kevin Formsma, Svetlana Gerdes, Elizabeth M Glass, Michael Kubal, Folker Meyer, Gary J Olsen (+14 others)
2008 BMC Genomics  
Herein we report the first genome sequence for Lactobacillus florum. L. florum 2F was isolated from Valencia orange leaves and is fructophilic, like other strains of this species. The draft genome of L. florum 2F contains 1,261,842 bp with a G؉C content of 41.5% in 46 contigs (>500 bp).
doi:10.1186/1471-2164-9-75 pmid:18261238 pmcid:PMC2265698 fatcat:5g42373tjfecxp44yqns7qwzoe

Glutathione Transferase π Plays a Critical Role in the Development of Lung Carcinogenesis following Exposure to Tobacco-Related Carcinogens and Urethane

Kenneth J. Ritchie, Colin J. Henderson, Xiu Jun Wang, Olga Vassieva, Dianne Carrie, Peter B. Farmer, Margaret Gaskell, Kevin Park, C. Roland Wolf
2007 Cancer Research  
Human cancer is controlled by a complex interaction between genetic and environmental factors. Such environmental factors are well defined for smoking-induced lung cancer; however, the roles of specific genes have still to be elucidated. Glutathione transferase P (GSTP) catalyzes the detoxification of electrophilic diol epoxides produced by the metabolism of polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP), a common constituent of tobacco smoke. Activityaltering polymorphisms in
more » ... p have therefore been speculated to be potential risk modifiers in lung cancer development. To clearly establish a role for GSTP in lung tumorigenesis, we investigated whether deletion of the murine Gstp genes (Gstp1 and Gstp2) alters susceptibility to chemically induced lung tumors following exposure to BaP, 3-methylcholanthrene (3-MC), and urethane. Gstp-null mice were found to have substantially increased numbers of adenomas relative to wildtype mice following exposure to all three compounds (8.3-, 4.3-, and 8.7-fold increase for BaP, 3-MC, and urethane, respectively). In Gstp-null mice, the capacity of pulmonary cytosol to catalyze conjugation of the BaP diol epoxide was significantly reduced. Concomitant with this, a significant increase in the level of BaP DNA adducts was measured in the lungs of null animals; however, no increase in DNA adducts was measured in the case of 3-MC exposure, suggesting that an alternative protective pathway exists. Indeed, significant differences in pulmonary gene expression profiles were also noted between wild-type and null mice. This is the first report to establish a clear correlation between Gstp status and lung cancer in vivo.
doi:10.1158/0008-5472.can-07-1764 pmid:17909032 fatcat:5ob4rlhv45g7ljoa2vbk2uj33i

An application of statistics to comparative metagenomics

Beltran Rodriguez-Brito, Forest Rohwer, Robert A Edwards
2006 BMC Bioinformatics  
Acknowledgements The authors thank Matt Cohoon, Sveta Gerdes, Andrei Osterman, Ross Overbeek, Rick Stevens, Olga Vassieva, Veronika Vonstein, Olga Zagnitko, and the other developers and annotators working  ... 
doi:10.1186/1471-2105-7-162 pmid:16549025 pmcid:PMC1473205 fatcat:vtldw4rruzc23bv6tr3g6m6oda

Draft Sequencing and Comparative Genomics of Xylella fastidiosa Strains Reveal Novel Biological Insights

A. Bhattacharyya
2002 Genome Research  
ACKNOWLEDGMENTS We thank members of the bioinformatics and genome analysis group at Integrated Genomics, specifically, Gordon Pusch, Lynn Jablonski, Olga Vassieva, Allen Bartman, and Warren Gardner for  ... 
doi:10.1101/gr.370702 pmid:12368248 pmcid:PMC187531 fatcat:uvswdbrl6rbhfefnkdgteildv4

Whole-genome comparative analysis of three phytopathogenic Xylella fastidiosa strains

A. Bhattacharyya, S. Stilwagen, N. Ivanova, M. D'Souza, A. Bernal, A. Lykidis, V. Kapatral, I. Anderson, N. Larsen, T. Los, G. Reznik, E. Selkov (+10 others)
2002 Proceedings of the National Academy of Sciences of the United States of America  
We thank members of the bioinformatics and genome analysis group at Integrated Genomics, including Gordon Pusch, Lynn Jablonski, Olga Vassieva, Allen Bartman, and Warren Gardner.  ... 
doi:10.1073/pnas.132393999 pmid:12205291 pmcid:PMC129457 fatcat:q7gtepdfnngtzdcpys7imcvanm

Conservation of the Biotin Regulon and the BirA Regulatory Signal in Eubacteria and Archaea

D. A. Rodionov
2002 Genome Research  
ACKNOWLEDGMENTS The authors are grateful to Andrei Osterman, Olga Vassieva, Sveta Gerdes, and Alexandra Rachmaninova for helpful discussions.  ... 
doi:10.1101/gr.314502 pmid:12368242 pmcid:PMC187538 fatcat:wexeqvqutfdjzj4hjkydbntc3q

Identification of retinoic acid as an inhibitor of transcription factor Nrf2 through activation of retinoic acid receptor alpha

X. J. Wang, J. D. Hayes, C. J. Henderson, C. R. Wolf
2007 Proceedings of the National Academy of Sciences of the United States of America  
Michael McMahon for the V5-mNrf2 construct, Olga Vassieva for discussions in the preparation of this manuscript, and Dianne Carrie for her assistance with the animal work.  ... 
doi:10.1073/pnas.0709483104 pmid:18048326 pmcid:PMC2148333 fatcat:r3hfhj3iirhezdtxoqx3crnaae

Carbohydrate metabolism genes and pathways in insects: insights from the honey bee genome

T. Kunieda, T. Fujiyuki, R. Kucharski, S. Foret, S. A. Ament, A. L. Toth, K. Ohashi, H. Takeuchi, A. Kamikouchi, E. Kage, M. Morioka, M. Beye (+3 others)
2006 Insect molecular biology (Print)  
Lee Beverly (UIUC) and Olga Vassieva (Fellowship for the Interpretation of Genomes, Chicago, IL) for helpful comments on the manuscript, and to Ross Overbeek (Fellowship for the Interpretation of Genomes  ... 
doi:10.1111/j.1365-2583.2006.00677.x pmid:17069632 pmcid:PMC1847477 fatcat:xwk5nvl4ffb73ljj6eipbd5gau

Comparative Genomics of Thiamin Biosynthesis in Procaryotes

Dmitry A. Rodionov, Alexey G. Vitreschak, Andrey A. Mironov, Mikhail S. Gelfand
2002 Journal of Biological Chemistry  
Acknowledgments-We are grateful to Andrei Osterman for attention, advice, and encouragement and to Tadhg Begley, Pieter Dorrestein, Iain Anders, and Olga Vassieva for critical reading of the manuscript  ... 
doi:10.1074/jbc.m208965200 pmid:12376536 fatcat:eynsnm3rtrdmzfpcuvpnj77c2a