Downregulation of Hepatic Cytochrome P450 3A in Mice Infected with Babesia microti

被引：12

作者：

Shimamoto, Yoshinori ^{[1
]}

Sasaki, Mizuki ^{[2
]}

Ikadai, Hiromi ^{[2
]}

Ishizuka, Mayumi ^{[4
]}

Yokoyama, Naoaki ^{[5
]}

Igarashi, Ikuo ^{[5
]}

Hoshi, Fumio ^{[3
]}

Kitamura, Hiroshi ^{[6
]}

机构：

[1] Kitasato Univ, Dept Vet, Sch Vet Med, Teaching Hosp, Towada, Aomori 0348628, Japan

[2] Kitasato Univ, Dept Vet Parasitol, Sch Vet Med, Towada, Aomori 0348628, Japan

[3] Kitasato Univ, Dept Small Anim Internal Med, Sch Vet Med, Towada, Aomori 0348628, Japan

[4] Hokkaido Univ, Toxicol Lab, Dept Environm Vet Sci, Grad Sch Vet Med, Sapporo, Hokkaido 0600818, Japan

[5] Obihiro Univ Agr & Vet Med, Natl Res Ctr Protozoan Dis, Obihiro, Hokkaido 0808555, Japan

[6] Nagoya City Univ, Dept Comparat & Expt Med, Grad Sch Med Sci, Mizuho Ku, Nagoya, Aichi 4678601, Japan

来源：

JOURNAL OF VETERINARY MEDICAL SCIENCE | 2012年 / 74卷 / 02期

关键词：

Babesia microti; CYP3A; cytochrome P450; downregulation; drug metabolism; NF-KAPPA-B; NUCLEAR RECEPTORS; MOUSE-LIVER; XENOBIOTIC RESPONSE; T-CELL; METABOLISM; EXPRESSION; MICROSOMES; GENE; PXR;

D O I：

10.1292/jvms.11-0036

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

0906 ;

摘要：

To investigate effects of Babesia infection on drug metabolism, we intraperitoneally inoculated B. microti into ICR mice and measured the expression and activity of hepatic cytochrome P450 (CYP) 3A, a major drug-metabolizing enzyme. Twelve days after infection, CYP3A11 mRNA, CYP3A protein and activity and mRNAs of nuclear receptors, which participate in CYP3A expression, were significantly reduced. These results suggest that B. microti infection suppresses CYP3A-dependent drug metabolism. Additionally, tumor necrosis factor (TNF)-alpha and nitric oxide synthase (NOS) 2 mRNAs were induced in the infected mouse liver. Since TNT-a is one of the potent mediators that induce NOS2 and repress CYP3A transcription, the possible involvement of TNF-alpha in this downregulation of CYP3A was discussed.

引用

页码：241 / 245

页数：5

共 34 条

[1]

Abramoff M.D., 2004, Biophotonics International, V11, P36

[2] Cytochromes P450 and metabolism of xenobiotics [J].

Anzenbacher, P ;

Anzenbacherová, E .

CELLULAR AND MOLECULAR LIFE SCIENCES, 2001, 58 (5-6) :737-747

[3] STUDIES ON THE PREGNENOLONE-16-ALPHA-CARBONITRILE-INDUCIBLE FORM OF RAT-LIVER MICROSOMAL CYTOCHROME-P-450 AND UDP-GLUCURONOSYLTRANSFERASE [J].

ARLOTTO, MP ;

SONDERFAN, AJ ;

KLAASSEN, CD ;

PARKINSON, A .

BIOCHEMICAL PHARMACOLOGY, 1987, 36 (22) :3859-3866

[4] Multiple mechanisms of ontogenic regulation of nuclear receptors during rat liver development [J].

Balasubramaniyan, N ;

Shahid, M ;

Suchy, FJ ;

Ananthanarayanan, M .

AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2005, 288 (02) :G251-G260

[5] Reduction in cytochrome P-450 enzyme expression is associated with repression of CAR (constitutive androstane receptor) and PXR (pregnane X receptor) in mouse liver during the acute phase response [J].

Beigneux, AP ;

Moser, AH ;

Shigenaga, JK ;

Grunfeld, C ;

Feingold, KR .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2002, 293 (01) :145-149

[6] IMPAIRED CYTOKINE RESPONSE IN MALE ICR SWISS MICE AFTER INFECTION WITH D-VARIANT OF ENCEPHALOMYOCARDITIS VIRUS [J].

BIGLEY, NJ ;

BLAY, RA ;

SMITH, RA .

DIABETES, 1987, 36 (12) :1408-1413

[7] Orphan nuclear receptors - new ligands and new possibilities [J].

Blumberg, B ;

Evans, RM .

GENES & DEVELOPMENT, 1998, 12 (20) :3149-3155

[8] Malaria downmodulates mRNA expression and catalytic activities of CYP1A2, 2E1 and 3A11 in mouse liver [J].

Carvalho, Renato Sampaio ;

Friedrich, Karen ;

De-Oliveira, Ana C. A. X. ;

Suarez-Kurtz, Guilherme ;

Paumgartten, Francisco J. R. .

EUROPEAN JOURNAL OF PHARMACOLOGY, 2009, 616 (1-3) :265-269

[9] Helper T cell and antibody responses to infection of CBA mice with Babesia microti [J].

Chen, DH ;

Copeman, DB ;

Burnell, J ;

Hutchinson, GW .

PARASITE IMMUNOLOGY, 2000, 22 (02) :81-88

[10] Regulation and induction of CYP3A11, CYP3A13 and CYP3A25 in C57BL/6J mouse liver [J].

Down, M. J. ;

Arkle, S. ;

Mills, J. J. .

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2007, 457 (01) :105-110

← 1 2 3 4 →