| |
ACTIVATION
OF MONO-OXYGENASE SYSTEMS |
|
|
| |
| |
|
Research Institute of Biology, Karazin
Kharkov National University, Ukraine.
Dietary restriction is the only
known experimental method to extend lifespan in mammals,
but the mechanisms of this phenomenon are still unknown.
It is determined that the keeping of animals on the calorie
restricted diet results in essential changes of a drug-metabolizing
enzymes contents, that is also confirmed by the change
of response of the enzyme system to thyroxine action.
As a whole, the results obtained will be coordinated with
the point of view, according to which the action mechanisms
of the dietary restriction consist in considerable change
of a wide spectrum of biochemical processes, including
the change of the level of monooxygenase system functioning.
|
|
|
Department of Anatomy and Public Health,
College of Veterinary Medicine, Texas A&M University,
College Station 77843, USA.
1. We characterized the dose-dependent
induction of the microsomal monooxygenase system by phenobarbital
(PB) and 3-methylcholanthrene (MC) in the female Fischer
344 rat, which was either calorie restricted (CR) or fed
ad libitum (AL). 2. Maximal induction of the major inducible
isozymes (2B1/2B2 or 1A1) in rat was achieved at the lowest
of the inducer doses employed (10 mg/kg body weight) in
both feeding groups. 3. The patterns of dose-dependent
PB induction and its magnitude differed between total
P450 induction and induction of catalytic activities in
AL and CR groups, whereas no differences between CR and
AL rat were found in either spectrally detected P450 or
EROD activity patterns of dose-dependent MC induction.
4. Calorie restriction increased the inducibility of some
hepatic drug-metabolizing enzyme activities. 5. Monoclonal
antibody-directed inhibition of MC-induced ethoxyresorufin
O-deethylation (EROD) was 55-60% at all induction levels
in AL rat and 65-70% in CR rat, while MAb inhibition of
PB-induced pentoxyresorufin O-depenthylation (PROD) averaged
about 55% in AL and 60% in CR rat.
|
|
|
Institute of Toxicology, National Taiwan
University, Taipei, Republic of China.
ABSTRACT: The effects of fasting
on liver, kidney, and lung monooxygenases were studied
using hamsters starved for 4 days. Fasting treatment increased
microsomal cytochrome P450 content and NADPH-cytochrome
P450 reductase activity in kidney and lung. The treatment
caused significant increases of aniline hydroxylation,
N-nitrosodimethylamine demethylation, and 7-ethoxycoumarin
O-deethylation activities in the liver, kidney, and lung.
Fasting caused a threefold increase of benzphetamine N-demethylation
activity in lung and a 25% increase in liver and had no
effect in kidney. Benzo[a]pyrene hydroxylation activities
in the fasted hamster liver, kidney, and lung were higher,
lower, and similar to the controls, respectively. Gel
electrophoresis of tissue microsomes from control and
fasted hamsters revealed that fasting enhanced the intensity
of protein band(s) in the P450 molecular weight region.
Immunoblotting of the microsomal proteins showed that
fasting induced a protein crossreactive with rabbit antibody
raised against human P450 2E1 in hamster liver, kidney,
and lung. Immunoblotting analysis using mouse monoclonal
antibody 2-66-3 raised against rat P450 2B1 revealed that
fasting induced an immunorelated protein preferentially
in hamster lung, with minimal effects on liver and kidney.
Protein blots probed with mouse monoclonal antibody 1-12-3
indicated that fasting induced a protein related to P450
1A1 in hamster liver, kidney, and lung. These results
demonstrate that fasting causes a variety of inductive
effects on the enzyme components and catalytic activities
of monooxygenase systems as well as on the P450s 2E, 2B,
and 1A in the hamster tissues.
|
|
|
