INDUCTION OF RAT HEPATIC MIXED-FUNCTION OXIDASES BY ACETONE AND OTHER PHYSIOLOGICAL KETONES - THEIR ROLE IN DIABETES-INDUCED CHANGES IN CYTOCHROME P450 PROTEINS

被引:31
作者
BARNETT, CR
PETRIDES, L
WILSON, J
FLATT, PR
IOANNIDES, C
机构
[1] UNIV SURREY,SCH BIOL SCI,DIV TOXICOL,MOLEC TOXICOL GRP,GUILDFORD GU2 5XH,SURREY,ENGLAND
[2] UNIV ULSTER,BIOMED SCI RES CTR,COLERAINE,LONDONDERRY BT5,NORTH IRELAND
[3] UNIV ULSTER,DEPT BIOL & BIOMED SCI,COLERAINE,LONDONDERRY BT5,NORTH IRELAND
关键词
D O I
10.3109/00498259209056694
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1. To evaluate the role of ketone bodies in diabetes-induced changes in hepatic cytochrome P450 composition, rats were treated with acetone, 3-hydroxybutyrate or 1,3-butanediol. 2. Treatment with acetone enhanced the rat hepatic 0-dealkylations of ethoxyresorufin and methoxyresorufin, and the hydroxylation of p-nitrophenol, but had no effect on lauric acid hydroxylation and ethylmorphine N-demethylation. Neither 3-hydroxybutyrate nor 1,3-butanediol modulated the metabolism of the above substrates. 3. Immunoblot analysis of hepatic microsomal proteins revealed that treatment with acetone increased the apoprotein levels of P4501A2, P4502B1/2 and P4502E1. 4. It is concluded that acetone is responsible, at least partly, for the diabetes-induced increase in hepatic microsomal P4501A2, P4502B1/2 and P4502E1 proteins but does not mediate the increases in the P4503A1 and P4504A1 proteins. On the basis of work from our own and other laboratories a mechanism for the diabetes-induced changes in hepatic cytochrome P450 proteins is proposed.
引用
收藏
页码:1441 / 1450
页数:10
相关论文
共 50 条
[31]  
Parker G., 1980, BIOCH BIOPHYSICS REG, P373
[32]  
PAST MR, 1983, RES COMMUN CHEM PATH, V40, P379
[33]   EFFECT OF DIABETES ON RAT-LIVER CYTOCHROME-P-450 - EVIDENCE FOR A UNIQUE DIABETES-DEPENDENT RAT-LIVER CYTOCHROME-P-450 [J].
PAST, MR ;
COOK, DE .
BIOCHEMICAL PHARMACOLOGY, 1982, 31 (20) :3329-3334
[34]   DETERMINATION OF CYTOCHROME-P-448 ACTIVITY IN BIOLOGICAL TISSUES [J].
PHILLIPSON, CE ;
GODDEN, PMM ;
LUM, PY ;
IOANNIDES, C ;
PARKE, DV .
BIOCHEMICAL JOURNAL, 1984, 221 (01) :81-88
[35]  
REINKE LA, 1985, DRUG METAB DISPOS, V13, P548
[36]   INTERACTIONS OF IMIDAZOLE ANTIFUNGAL AGENTS WITH PURIFIED CYTOCHROME-P-450 PROTEINS [J].
RODRIGUES, AD ;
GIBSON, GG ;
IOANNIDES, C ;
PARKE, DV .
BIOCHEMICAL PHARMACOLOGY, 1987, 36 (24) :4277-4281
[37]   GROWTH-HORMONE RESPONSIVENESS INVIVO AND INVITRO TO GROWTH-HORMONE RELEASING-FACTOR IN THE SPONTANEOUSLY DIABETIC BB WISTAR RAT [J].
SERRI, O ;
BRAZEAU, P .
NEUROENDOCRINOLOGY, 1987, 46 (02) :162-166
[38]  
SONG BJ, 1986, J BIOL CHEM, V261, P6689
[39]   DETERMINATION OF GLUCOSE BY AN AUTOMATIC ANALYSER [J].
STEVENS, JF .
CLINICA CHIMICA ACTA, 1971, 32 (02) :199-&
[40]   MULTIPLE FORMS OF HEPATIC CYTOCHROME-P-450 - PURIFICATION, CHARACTERIZATION AND COMPARISON OF A NOVEL CLOFIBRATE-INDUCED ISOZYME WITH OTHER MAJOR FORMS OF CYTOCHROME-P-450 [J].
TAMBURINI, PP ;
MASSON, HA ;
BAINS, SK ;
MAKOWSKI, RJ ;
MORRIS, B ;
GIBSON, GG .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1984, 139 (02) :235-246