Acetone-dependent regulation of cytochromes P4502E1 and P4502B1 in rat nasal mucosa.
The inducibility and molecular regulation of cytochrome P4502E1 (CYP2E1) has been examined in nasal mucosa of rats after acetone treatment and compared to that of cytochrome P4502B1 (CYP2B1). Twenty-four hours following treatment with acetone (5 mL/kg) for 2 days, the amount of CYP2E1 as well as the rate of microsomal 4-nitrophenol hydroxylase activity had increased by a factor of 2-3, in microsomes isolated from nasal mucosa. The increase in CYP2E1 was accompanied by a corresponding increase of CYP2E1 mRNA, as determined by northern and slot blot analyses. In contrast, hepatic and renal CYP2E1 mRNA, studied in the same rats, did not increase, despite the fact that the amount of CYP2E1 was increased 3- and 5-fold, respectively. The amount of CYP2B1, an isozyme known as acetone-inducible in other tissues, decreased significantly by acetone, as detected by immunoblot analysis. After 48 hr, the amount of CYP2E1 enzyme, the level of CYP2E1 mRNA and the rate of 4-nitrophenol hydroxylase activity had returned to normal levels, whereas in liver and kidneys the immunoreactive protein remained 3-4-fold higher than control. The results indicate that acetone does not regulate CYP2E1 in nasal mucosa by post-translational mechanisms, in contrast to the situation observed in liver and kidneys. This indicates a tissue-specific expression of post-translational regulatory systems responsible for P450 stabilization. Furthermore, nasal CYP2B1 also seems to be regulated in a tissue-specific manner by acetone.
Longo
V
V
Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
Ingelman-Sundberg
M
M
D000096:Acetone / Q000494:pharmacology*; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007668:Kidney / Q000187:drug effects; D008099:Liver / Q000187:drug effects; D008297:Male; D009297:Nasal Mucosa / Q000187:drug effects* / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000096:Acetone; D003577:Cytochrome P-450 Enzyme System