Regulation of CYP2D expression in rat brain by toluene.
We investigated the expressional regulation of cytochrome P450 (CYP) 2D isoforms in rat brain by toluene. Toluene (10 mmol/kg) was injected intraperitoneally into male rats daily for 3 days. CYP2D4 level in the brain was determined by Western blotting. The level of CYP2D4 in the brain and the catalytic activity specific for this isoform were significantly increased by toluene administration. The expressions of CYP2D mRNAs in the brain were quantified by real time PCR. The mRNA level of CYP2D4 increased similar to the expression of the protein and enzymatic activity. These results showed that CYP2D4 was transcriptionally induced by toluene administration for 3 days. This is the first report that subacute exposure to toluene activated the expression of CYP2D4 mRNA in the brain. The response of CYP2D4 expression to toluene is thought to relates to the regulation of the physiological and pharmacological functions of CYP2D isoforms in the brain.
Mizuno
Dai
D
Department of Chemical Biology, Osaka City University Medical School, Japan.
Hiroi
Toyoko
T
Ng
Pohshing
P
Kishimoto
Wataru
W
Imaoka
Susumu
S
Funae
Yoshihiko
Y
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis / Q000235:genetics*; D001921:Brain / Q000201:enzymology*; D004983:Ethanolamines / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D008297:Male; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014050:Toluene / Q000494:pharmacology*
D004983:Ethanolamines; D012333:RNA, Messenger; D014050:Toluene; C010831:bufuralol; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C115670:Cyp2d4 protein, rat