CYTAKINE-MEDIATED PRODUCTION OF NITRIC-OXIDE IN ISOLATED RAT HEPATOCYTES IS DEPENDENT ON CYTOCHROME P-450III ACTIVITY

被引：17
作者：
KUO, PC
ABE, KY
机构：
来源：
FEBS LETTERS | 1995年 / 360卷 / 01期
关键词：
NITRIC OXIDE; CYTOCHROME P-450; CIMETIDINE; CLOTRIMAZOLE; RAT HEPATOCYTE;
D O I：
10.1016/0014-5793(95)00067-J
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
To investigate the role of the cytochrome P-450 system in NO synthesis, cytochrome P-450IIIA, IIE and IA activities were specifically inhibited by cimetidine (IIIA), clotrimazole (IIIA), benzoflavone (IA) and disulfiram (IIE) in a model of cultured rat hepatocytes. Cytokine-induced NO synthesis was significantly decreased in the presence of cimetidine and clotrimazole. Kinetic analysis revealed a non-competitive mode of inhibition (K-i = 21 mM, cimetidine; K-i = 13 mu M, clotrimazole), Reverse transcriptase-PCR and immunoblot analysis revealed no significant change in steady state levels of iNOS mRNA and protein expression with P-450IIIA inhibition. Purified iNOS enzyme activity was not altered. These data suggest that cytokine-mediated hepatocyte synthesis of NO is dependent upon P-450IIIA activity, which functions in a post-translational capacity.
引用
收藏
页码：10 / 14
页数：5
相关论文
共 19 条
[1]   INTERLEUKIN-1 ACTIVATES SOLUBLE GUANYLATE-CYCLASE IN HUMAN VASCULAR SMOOTH-MUSCLE CELLS THROUGH A NOVEL NITRIC OXIDE-INDEPENDENT PATHWAY [J].
BEASLEY, D ;
MCGUIGGIN, M .
JOURNAL OF EXPERIMENTAL MEDICINE, 1994, 179 (01) :71-80
[2]   MODULATION OF NITROGEN-OXIDE SYNTHESIS INVIVO - NG-MONOMETHYL-L-ARGININE INHIBITS ENDOTOXIN-INDUCED NITRITE NITRATE BIOSYNTHESIS WHILE PROMOTING HEPATIC DAMAGE [J].
BILLIAR, TR ;
CURRAN, RD ;
HARBRECHT, BG ;
STUEHR, DJ ;
DEMETRIS, AJ ;
SIMMONS, RL .
JOURNAL OF LEUKOCYTE BIOLOGY, 1990, 48 (06) :565-569
[3]  
Bishop G A, 1993, Transpl Immunol, V1, P253, DOI 10.1016/0966-3274(93)90033-5
[4]   ONTOGENY OF RABBIT LIVER CYTOCHROME-P450 - EVIDENCE FOR A CYTOCHROME-P450-IIE (3A)-RELATED FORM PREVAILING DURING THE POSTNATAL-PERIOD [J].
BONFILS, C ;
COMBALBERT, J ;
PINEAU, T ;
ANGEVIN, J ;
LARROQUE, C ;
DERANCOURT, J ;
CAPONY, JP ;
MAUREL, P .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 188 (01) :187-194
[5]   FORMATION OF NITROGEN-OXIDES AND CITRULLINE UPON OXIDATION OF N-OMEGA-HYDROXY-L-ARGININE BY HEMEPROTEINS [J].
BOUCHER, JL ;
GENET, A ;
VADON, S ;
DELAFORGE, M ;
MANSUY, D .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 184 (03) :1158-1164
[6]   CYTOCHROME P450 CATALYZES THE OXIDATION OF N-OMEGA-HYDROXY-L-ARGININE BY NADPH AND O-2 TO NITRIC-OXIDE AND CITRULLINE [J].
BOUCHER, JL ;
GENET, A ;
VADON, S ;
DELAFORGE, M ;
HENRY, Y ;
MANSUY, D .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 187 (02) :880-886
[7]  
COMBALBERT J, 1989, DRUG METAB DISPOS, V17, P197
[8]   MULTIPLE CYTOKINES ARE REQUIRED TO INDUCE HEPATOCYTE NITRIC-OXIDE PRODUCTION AND INHIBIT TOTAL PROTEIN-SYNTHESIS [J].
CURRAN, RD ;
BILLIAR, TR ;
STUEHR, DJ ;
OCHOA, JB ;
HARBRECHT, BG ;
FLINT, SG ;
SIMMONS, RL .
ANNALS OF SURGERY, 1990, 212 (04) :462-471
[9]  
DEMONTELLANO PRO, 1986, CYTOCHROME P450 STRU, P273
[10]   OMEPRAZOLE IS AN ARYL HYDROCARBON-LIKE INDUCER OF HUMAN HEPATIC CYTOCHROME-P450 [J].
DIAZ, D ;
FABRE, I ;
DAUJAT, M ;
SAINTAUBERT, B ;
BORIES, P ;
MICHEL, H ;
MAUREL, P .
GASTROENTEROLOGY, 1990, 99 (03) :737-747
12