Molecular mechanism investigation of phenobarbital-induced serum cholesterol elevation in rat livers by microarray analysis.

作者: Naoki Kiyosawa , Kohji Tanaka , Jun Hirao , Kazumi Ito , Noriyo Niino

DOI: 10.1007/S00204-004-0565-0

关键词:

摘要: Phenobarbital (PB) increases serum total cholesterol levels in rodents and humans. To investigate the underlying molecular mechanisms, we performed a microarray analysis on liver of rats treated repeatedly with 100 mg/kg PB, examined blood chemistry. The concentration non-esterified fatty acids was decreased from day 1 to 14 except for 7, that increased 4 14. ketone bodies triglycerides Transcript content glycolytic genes by PB treatments, while lipoprotein lipase continuously increased, suggesting notion repetitive treatments impaired glycolysis stimulated lipolysis liver. hypothesis using previously reported flux-balance model. increase mRNA malic enzyme after treatment agreed well model result, validity our hypothesis. findings also suggested there an abundance acetyl-CoA shortage products repeated treatments. Although ketogenesis would normally occur under such cellular conditions, it only weakly observed presumably owing decrease HMG-CoA synthase content. On other hand, several cholesterogenic slightly induced Thus, chemistry results cholesterogenesis rat livers, which may have contributed elevation concentration.

参考文章(41)
Sonal P. Sanghani, Wilhelmina I. Davis, Natividad G. Dumaual, Alan Mahrenholz, William F. Bosron, Identification of microsomal rat liver carboxylesterases and their activity with retinyl palmitate FEBS Journal. ,vol. 269, pp. 4387- 4398 ,(2002) , 10.1046/J.1432-1033.2002.03121.X
M Hijikata, N Ishii, H Kagamiyama, T Osumi, T Hashimoto, Structural analysis of cDNA for rat peroxisomal 3-ketoacyl-CoA thiolase. Journal of Biological Chemistry. ,vol. 262, pp. 8151- 8158 ,(1987) , 10.1016/S0021-9258(18)47542-4
M J Goldman, D W Back, A G Goodridge, Nutritional regulation of the synthesis and degradation of malic enzyme messenger RNA in duck liver. Journal of Biological Chemistry. ,vol. 260, pp. 4404- 4408 ,(1985) , 10.1016/S0021-9258(18)89279-1
Naoko MINAMI-ISHII, Shigeru TAKETANI, Takashi OSUMI, Takashi HASHIMOTO, Molecular cloning and sequence analysis of the cDNA for rat mitochondrial enoyl-CoA hydratase FEBS Journal. ,vol. 185, pp. 73- 78 ,(1989) , 10.1111/J.1432-1033.1989.TB15083.X
Thomas H. Rushmore, A.-N. Tony Kong, Pharmacogenomics, regulation and signaling pathways of phase I and II drug metabolizing enzymes. Current Drug Metabolism. ,vol. 3, pp. 481- 490 ,(2002) , 10.2174/1389200023337171
Albert J. Ketterman, Susan M. Pond, Charles E. Becker, The effects of differential induction of cytochrome P-450, carboxylesterase and glutathione S-transferase activities on malathion toxicity in mice. Toxicology and Applied Pharmacology. ,vol. 87, pp. 389- 392 ,(1987) , 10.1016/0041-008X(87)90243-2
Didier Brault, Lydie Noé, Jacqueline Etienne, Jocelyne Hamelin, Alain Raisonnier, Aziz Souli, Jean-Claude Chuat, Isabelle Dugail, Annie Quignard-Boulangé, Marcelle Lavau, Francis Galibert, Sequence of rat lipoprotein lipase-encoding cDNA. Gene. ,vol. 121, pp. 237- 246 ,(1992) , 10.1016/0378-1119(92)90127-B
Kazuo Kanai, Jun Watanabe, Satoshi Fujimoto, Shinsuke Kanamura, Quantitative analysis of smooth endoplasmic reticulum proliferation in periportal, midzonal and perivenular hepatocytes of mice after administration of phenobarbital Experimental and Toxicologic Pathology. ,vol. 45, pp. 199- 203 ,(1993) , 10.1016/S0940-2993(11)80387-8
Fausto G. HEGARDT, Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase: a control enzyme in ketogenesis Biochemical Journal. ,vol. 338, pp. 569- 582 ,(1999) , 10.1042/BJ3380569