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Brain mitochondrial cytochromes P450: xenobiotic metabolism, presence of multiple forms and their selective inducibility.
- Source :
-
Archives of biochemistry and biophysics [Arch Biochem Biophys] 1995 Jun 20; Vol. 320 (1), pp. 73-83. - Publication Year :
- 1995
-
Abstract
- The capability of rat brain mitochondria to metabolize a variety of xenobiotics was examined. The presence of cytochrome P450 (P450) and associated monooxygenase activities were estimated in isolated rat brain mitochondria and compared with the corresponding activities in microsomes. Total P450 content in brain mitochondria from naive rats was twice that of the corresponding microsomal level. The ability of brain mitochondria to metabolize the potent carcinogen N-nitrosodimethylamine was more than twofold that of the corresponding microsomal activity, while the 7-ethoxycoumarin-O-deethylase activity was significantly lower in mitochondria. Immunoblot experiments using antisera to purified rat liver microsomal P450s, namely P450 (2B1/2B2), P4501A1, and P4502E1, and purified phenobarbital-inducible rat brain P450, revealed the presence of immunoreactive bands in isolated brain mitochondria. These various antibodies to P450 inhibited the brain mitochondrial monooxygenase activities to significant, though varying extent. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450 associated monooxygenase activities, although it completely inhibited the corresponding microsomal activities. Chronic ethanol administration resulted in twofold induction of total P450 content and the monooxygenase activities known to be mediated by P4502E1, such as N-nitrosodimethylamine-N-demethylase and p-nitrophenol hydroxylase in brain mitochondria. Pretreatment of animals with phenobarbital resulted in the induction of aminopyrine N-demethylase activity in brain mitochondria. The study demonstrates the presence of multiple forms of P450 in the rat brain mitochondria, their inducibility, and their capability to metabolize xenobiotics.
- Subjects :
- 7-Alkoxycoumarin O-Dealkylase antagonists & inhibitors
7-Alkoxycoumarin O-Dealkylase metabolism
Alcoholism metabolism
Aminopyrine N-Demethylase antagonists & inhibitors
Aminopyrine N-Demethylase metabolism
Animals
Brain drug effects
Brain ultrastructure
Cytochrome P-450 CYP2E1
Cytochrome P-450 Enzyme Inhibitors
Cytochrome P-450 Enzyme System biosynthesis
Enzyme Induction drug effects
In Vitro Techniques
Male
Microscopy, Electron
Microsomes metabolism
Microsomes ultrastructure
Mitochondria metabolism
Mitochondria ultrastructure
Mixed Function Oxygenases antagonists & inhibitors
Mixed Function Oxygenases metabolism
Oxidoreductases, N-Demethylating antagonists & inhibitors
Oxidoreductases, N-Demethylating metabolism
Phenobarbital pharmacology
Rats
Rats, Wistar
Brain metabolism
Cytochrome P-450 Enzyme System metabolism
Xenobiotics metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0003-9861
- Volume :
- 320
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Archives of biochemistry and biophysics
- Publication Type :
- Academic Journal
- Accession number :
- 7793987
- Full Text :
- https://doi.org/10.1006/abbi.1995.1344