Different expression of hepatic and renal cytochrome P450s between the streptozotocin-induced diabetic mouse and rat.
1. Since limited information is available about alterations of cytochrome P450 levels in diabetic animals other than rat, expression of P450s in the liver and kidney of the streptozotocin (STZ)-induced diabetic mouse was investigated. 2. The mRNA levels of CYP2B10, 3A11, 4A10 and 4A14 in the liver were increased in the STZ-induced diabetic mouse of both sexes. The CYP2B9 mRNA level was increased in the liver of the male diabetic mouse. These alterations were observed even at 2 weeks after administration. Insulin treatment restored these changes. The findings were consistent with changes reported in rat. 3. The levels of hepatic CYP1A2 and 2E1 and renal 2E1 and 4A did not change in the diabetic mouse at any time-point examined. No changes were seen in CYP2A- or 2C-related proteins in the diabetic mouse. These findings were in contrast to those in rat. 4. The results indicate that mouse P450s respond to insulin-dependent diabetes mellitus differently from those of the rat, and suggest that the expression of P450s in diabetes is not generally the same across animal species.
Sakuma
T
T
Department of Toxicology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharmaceutical University, Japan. tsakuma@ms.toyama-mpu.ac.jp
Honma
R
R
Maguchi
S
S
Tamaki
H
H
Nemoto
N
N
D000818:Animals; D000900:Anti-Bacterial Agents; D001189:Aryl Hydrocarbon Hydroxylases; D001786:Blood Glucose / Q000378:metabolism; D002384:Catalysis; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis* / Q000737:chemistry* / Q000378:metabolism; D000072467:Cytochrome P450 Family 2; D000072470:Cytochrome P450 Family 4; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D015151:Immunoblotting; D007668:Kidney / Q000201:enzymology*; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000096:biosynthesis; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors; D013250:Steroid Hydroxylases; D013311:Streptozocin; D013997:Time Factors
D000900:Anti-Bacterial Agents; D001786:Blood Glucose; C436963:Cyp4a14 protein, mouse; D020033:Protein Isoforms; D012333:RNA, Messenger; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C101679:Cyp2b10 protein, mouse; D000072467:Cytochrome P450 Family 2; D000072470:Cytochrome P450 Family 4