Age-dependent changes in liver microsomal
cytochrome P-450.
Compiled by Andrey L. Sukhodub. All comments are welcomed.
last modified:
|
CYP P-450 |
Species |
Character of changes observed |
Method of estimation used |
Ref |
|
IA1 |
rat |
Absent in fetal liver till 14 day of pregnancy |
IMA * |
|
|
|
|
From 15th day of pregnancy constitutive gene expression
and further developmental mRNA accumulation occurs |
mRNA |
|
|
|
|
Detected at low levels in rats of both sexes at ages 1 week-24 months. |
IMA, 6b-testosterone-hydroxylase |
|
|
|
|
Remain unchanged in 12-36 months period |
IMA |
|
|
|
hamster |
Peak expression was observed in 6-month old hamsters and declined in older ones |
IMA |
|
|
|
mouse |
In B10.RIII mice progressively decrease between 4 and 28
months; in C57BL/10 mice little or no changes with age |
mRNA |
|
|
|
rabbit |
Absent in embryos, in newborn - low level; sharply accumulates till 1-2 months after birth; maximal level in 2-6 months, then decline |
mRNA |
|
|
|
man |
In adult liver microsomes was not detected. Located in lungs and placenta. |
IMA |
|
|
|
|
Immunoreactive antibodies detected in fetal liver. |
IMA |
|
|
IA2 |
rat |
Constitutive level versus total content of P-450 is higher in 1-day then in 15-day rats, but the amount of immunoreactive form is not depends upon age |
IMA |
|
|
|
|
Detected at low levels in rats of both sexes and ages (1 week-24 months) |
IMA, 6b-testosterone-hydroxylase |
|
|
|
|
Remains unchanged in the age 12-36 months |
IMA, mRNA |
|
|
|
hamster |
Peak expression was observed in 6-month old hamsters and declined in older ones |
IMA |
|
|
|
mouse |
Decrease between age 4-5 months and 30-31 months |
mRNA |
|
|
|
rabbit |
Present at low level or absent in the new born animal up to week 3, sharply accumulated between weeks 3 and 4 to reach a maximum by week 2. After 2nd month of life begin to fall. |
mRNA, IMA |
|
|
|
man |
Absent in the microsomes from fetal and neonatal livers. Increased in infants aged 1-3 months to attain 50% of the adult value at one year. |
IMA, imipramine demethylation, mRNA |
|
|
|
|
Unaltered with advancing age. Up to 60-fold variability between livers. |
IMA |
|
|
|
|
Activity falls in elderly |
caffeine clearance |
|
|
IB1 |
man |
The level of expression was very low in adult liver and only three out of six fetal livers expressed CYP1B1. |
mRNA |
|
|
IIA1 |
rat |
The level was maximal at 3 weeks of age in rats of both sexes |
IMA, testosterone 7a-hydroxylation |
|
|
|
|
In males decrease in postsuckling period |
testosterone 7a-hydroxylation |
|
|
|
|
The level and activity elevated in the old rats. Female predominant |
IMA, mRNA, testosterone 7a-hydroxylation |
|
|
IIA2 |
rat |
Detected in male rats only and was induced
developmentally. Disappeared at 24 months of age. |
IMA, testosterone 15a-hydroxylation |
|
|
|
|
Had no changes with aging |
IMA |
|
|
IIA6 |
rat |
3-week-old rats had the highest activity |
coumarin 7-hydroxylation |
|
|
|
man |
No differences between perinatal and infant and after infancy patients |
IMA |
|
|
|
|
About 4% of total content. Minor form. Large, (up to 170-fold) variability. |
IMA, specific probes |
|
|
IIB1/B2 |
rat |
4 fold increase in 24 hours after birth |
mRNA |
|
|
|
|
Decrease with aging |
mRNA |
|
|
|
|
Detected at low levels in rats of both sexes at 1 week to 24 months. Had no changes with aging |
IMA, testosterone 16b-hydroxylation |
|
|
|
hamster |
Content reached the maximum at the age of 6 months and maintained almost the same level thereafter (18 month-old) |
IMA |
|
|
IIB4 |
rabbit |
Developmentally increase in postnatal period till 2
months. In 2-6 months period the level is constant, then decrease |
IMA |
|
|
IIB6 |
man |
Expressed highly in subjects over 1 year old. |
IMA |
|
|
|
|
The minor P-450 form (less then 1% of total content) |
IMA, specific substrates |
|
|
IIC3 |
rabbit |
Increased in postnatal period between 2-3 weeks, then between 1-2 months |
IMA |
|
|
IIC6 |
rat |
In males appears in a 4 weeks after birth, then permanently increase between 4-12 weeks. In females mRNA discovered in a small amounts on the 2 week, the level increase till 4 weeks old, after 7 weeks begin to fall. |
mRNA |
|
|
|
|
The amount is equal in male and female liver. |
IMA |
|
|
|
hamster |
Peak expression was observed in 6-month old hamsters and declined in older ones |
IMA |
|
|
IIC7 |
rat |
Increases gradually over the first 6 weeks of life. |
mRNA |
|
|
|
|
The content increase from less then 1% in the young (3 weeks old) males and females to 7-14% in adult (6 weeks). Female predominant. |
IMA |
|
|
IIC8 |
man |
Absent in fetal liver. Appears in a month after birth. Bimodal distribution in the liver. |
IMA, mRNA |
|
|
IIC9 |
man |
Absent in fetal liver. Appears in a month after birth. |
IMA, mRNA |
|
|
|
|
Had no changes with age |
IMA |
|
|
IIC11 |
rat |
Detected in male rats only and induced developmentally. Disappears at 24 months of age. |
IMA, testosterone 2a-hydroxylation |
|
|
|
|
Dramatic increase at puberty, between 4,5-5,5 weeks of life. |
mRNA |
|
|
|
hamster |
Content reached the maximum at the age 6 month and maintained almost the same level thereafter (18 month-old) |
IMA |
|
|
IIC12 |
rat |
Female-specific form. Induced developmentally in female
rats and was also detected in male rats at 3 weeks and 24 months of age. |
testosterone 15a-hydroxylation |
|
|
IIC13 |
rat |
The content increase from 1% in 3 weeks animals to 17% in
6 weeks old of total P-450 content. Male predominant. |
IMA |
|
|
IIC18 |
man |
Absent in fetal liver and appears in 1 months after birth. Polymorphic. |
IMA, mRNA |
|
|
IIC23 |
rat |
Maximal expression in early neonates and remained quite stable. |
mRNA |
|
|
IID6 |
man |
Appears soon after birth. |
IMA |
|
|
|
|
Had no changes with age. |
IMA |
|
|
|
|
About 2% of the total P-450 content. Polymorphic. |
IMA, specific substrates |
|
|
IIE1 |
rat |
Had a little volume or absent in fetal liver, increase in
a 4 days after birth and remains high during the first 17 days of neonate. |
N-nitrosodimethylamine demethylation |
|
|
|
|
In postsuckling period decrease more in males then in females. Female predominant. |
|
|
|
|
hamster |
Peak expression was observed in 6-month old hamsters and declined in older ones |
IMA |
|
|
|
rabbit |
Not detectable until 2 weeks and increase rapidly to
approximately twice the adult level at 5 weeks of age. |
mRNA |
|
|
|
|
Adult age isoform. |
|
|
|
|
man |
Protein and its associated activity could not be detected
in fetal liver and rise during the first few hours following birth independently
of the gestational age (between 25-40 weeks). During this period mRNA level
remains fairly low. From 1 months to 1 year the protein content gradually
increases and is accompanied by the accumulation of mRNA. |
IMA, mRNA |
|
|
|
|
Present in liver samples from perinatal, infant and 1 year
old patients and no differences was observed between these groups. |
IMA |
|
|
|
|
In fetal liver present a protein immunoreactive with CCYP2E1 antibodies that exhibited a slightly lower molecular weight than that found in adult liver samples.. |
IMA |
|
|
|
|
Negative association between age and protein content. |
IMA |
|
|
|
|
About 7% from total P-450 content in adult liver. Up to 50-fold variability. |
IMA |
|
|
IIE2 |
rabbit |
Specific young age isoform |
IMA |
|
|
|
|
mRNA detectable immediately after birth and reaches
slightly greater than the adult level at 2 weeks of age. |
mRNA |
|
|
IIIA1 |
rat |
The main constitutive male form. 10 fold increase during the first 24 hours after birth. |
mRNA |
|
|
IIIA2 |
rat |
Constitutively expressed early after birth and characterized by an extinction in the adult females after 3 weeks. In males disappeared when the rats were 24 months of age. In female was detected only at 1 and 3 weeks of age. |
IMA, testosterone 6b-hydroxylation, mRNA |
|
|
|
hamster |
Peak expression was observed in 6-month old hamsters and declined in older ones |
IMA |
|
|
IIIA3/4 |
man |
Absent in fetal liver |
IMA |
|
|
|
|
Extremely weak in the fetus and began to raise after birth to reach 30-40% of the adult activity after 1 month. mRNA accumulation displays a similar pattern of evolution. Major P-450 isoform present in the adult liver. Up to 60-fold variability. Constitutive, about 50% of total content. |
testosterone 6b-hydroxylation, mRNA, IMA |
|
|
IIIA5 |
man |
Detected in statistically higher percentage of children
and adolescents (19 years old and under. Detected in 1 of 10 man fetal
livers. Polymorphic - present in 27% of population. |
IMA |
|
|
IIIA6 |
rabbit |
Present at low level in the new born animal up to week 3, sharply accumulated between weeks 3 and 4 to reach maximum by week 4 and decreased in adult. |
mRNA |
|
|
IIIA7 |
mice |
The mRNA epression could be detected as early as the 15th embryonic day and increased gradually with advancing gestation, but then so after birth. The protein epression was also detectable postnatally and increased. |
MRNA, IMA |
|
|
|
man |
Expressed in the fetal liver. Activity high in the fetal
liver and maximal during the first week following birth before to
progressively decline and reached a very low level in adult livers. |
16a-hydroxylation of dehydroepiandrosterone, IMA |
|
|
|
|
Found in all tested samples of fetal liver as in 7 of 13
adult livers. Expressed at similar levels in fetal liver from either gender. |
mRNA |
|
|
IIIA9 |
rat |
Detected only in adult rats, which a nearly twofold higher expression in females. |
mRNA |
|
|
IIIA18 |
rat |
Observed before and after puberty at fairly constant |
mRNA |
|
|
IIIA23 |
|
levels that were about 20% higher in males than in females |
|
|
|
IVA1 |
hamster |
Level did not change from 3 to 6 months, and then declined to about 40% of the younger level at 12 and 18 months of age. |
IMA |
|
|
IVA2 |
rat |
Detected in male rats only and was induced
developmentally. Disappeared in male at 24 months of age. |
IMA |
|
|
IVA3 |
rat |
Induced developmentally and detected at similar level in rats of both sexes at age 1 week-2 months. |
IMA |
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