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Constitutive androstane receptor agonist initiates metabolic activity required for hepatocite proliferation

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1. Title Title of document Constitutive androstane receptor agonist initiates metabolic activity required for hepatocite proliferation
2. Creator Author's name, affiliation, country M. E Mazin; Novosibirsk State University;Federal Research Center of Fundamental and Translational Medicine
2. Creator Author's name, affiliation, country A. M Perevalova; Novosibirsk State University
2. Creator Author's name, affiliation, country A. A Yarushkin; Federal Research Center of Fundamental and Translational Medicine
2. Creator Author's name, affiliation, country Y. A Pustylnyak; Novosibirsk State University
2. Creator Author's name, affiliation, country A. D Rogachev; Novosibirsk State University
2. Creator Author's name, affiliation, country E. A Prokopyeva; Novosibirsk State University;Federal Research Center of Fundamental and Translational Medicine
2. Creator Author's name, affiliation, country L. F Gulyaeva; Novosibirsk State University;Federal Research Center of Fundamental and Translational Medicine
2. Creator Author's name, affiliation, country V. O Pustylnyak; Novosibirsk State University;Federal Research Center of Fundamental and Translational Medicine
3. Subject Discipline(s)
3. Subject Keyword(s) TCPOBOP; constitutive androstane receptor; TCPOBOP; liver; hepatocyte; metabolomics
4. Description Abstract Constitutive androstane receptor (CAR, NR1I3) activation by chemical compounds evokes liver hyperplasia in rodent. 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP), a mouse CAR agonist, is most commonly used to study chemically induced liver hyperplasia and hepatocyte proliferation in vivo. TCPOBOP is potent murine liver chemical mitogen, which induces rapid direct liver hyperplasia independent of liver injury. In recent years, a lot of data has been accumulated on the transcription program that characterizes TCPOBOP-induced hepatocyte proliferation. However, there are scarce data about metabolic requirements of hepatocytes dividing upon treatment with xenobiotics. In present study, we employed liquid chromatography - mass spectrometry technology combined with statistical analysis to develop a metabolite profile of small biomolecules, to identify key metabolic changes in male mouse liver tissue after TCPOBOP administration. Analysis of biochemical pathways of the differentially affected metabolites in mouse livers demonstrated significant TCPOBOP-mediated enrichment of several processes including those relevant to nucleotide metabolism, amino acid metabolism, and energy substrate metabolism. Our findings provide evidence to support the conclusion that CAR agonist, TCPOBOP, initiates an intracellular program that promotes the global coordinated metabolic activities required for hepatocyte proliferation. Our metabolic data may provide novel insight into the biological mechanisms that occur during TCPOBOP-induced hepatocyte proliferation in mice.
5. Publisher Organizing agency, location The Russian Academy of Sciences
6. Contributor Sponsor(s)
7. Date (DD-MM-YYYY) 15.12.2023
8. Type Status & genre Peer-reviewed Article
8. Type Type Research Article
9. Format File format
10. Identifier Uniform Resource Identifier https://rjsocmed.com/0320-9725/article/view/665588
10. Identifier Digital Object Identifier (DOI) 10.31857/S032097252308002X
10. Identifier eLIBRARY Document Number (EDN) IHUBDC
11. Source Title; vol., no. (year) Biohimiâ; Vol 88, No 8 (2023)
12. Language English=en ru
13. Relation Supp. Files
14. Coverage Geo-spatial location, chronological period, research sample (gender, age, etc.)
15. Rights Copyright and permissions Copyright (c) 2023 Russian Academy of Sciences