Developmental expression of CYP1A1, CYP1A2 and CYP3A6 in the rabbit have been studied. Cytochromes P450IA1, P450IA2 and P450IIIA6 exhibited comparable patterns of developmental expression. Present at ...low level (< 0.05 nmol/mg) in the new born animal up to week 3, these proteins sharply accumulated between weeks 3 and 4 to reach a maximum by week 4 (P450IA1, 0.2 nmol/mg; P450IA2, 0.8 nmol/mg; P450IIIA6, 0.12 nmol/mg) and decreased in the adult (P450IA1, 0.2 nmol/mg; P450IA2, 0.4 nmol/mg; P450IIIA6, 0.09 nmol/mg). Cytochromes P450IA1 and P450IA2 were not expressed in the untreated fetus. Onset of CYP3A6 gene expression occurred at day 30 of gestation and both transcription and mRNA accumulation were transplacentally inducible by rifampicin only shortly before birth, i.e. after treatment of the females between days 28 and 30 of gestation. Both long (1.85 kb) and short (1.7 kb) mRNA transcripts were expressed in untreated or rifampicin‐treated fetuses. CYP3A6 gene expression was also induced by rifampicin in 1‐week‐old and 2‐week‐old animals. Developmental expression of CYP1A1 and CYP1A2 genes was shown to be closely related to the diet change accompanying weaning which occurs at weeks 3–4. In animals subjected to either delayed (week 6) or early (week 2) weaning, sharp accumulation of messages, proteins and related activities were delayed or anticipated accordingly with respect to normal weaning. Artificially scheduled weaning gave similar results when repeated with biological‐grade lucern (grown in the absence of chemical fertilizers, pesticides, etc.), the main constituent of commercial rabbit chow. While CYP3A6 gene expression could be brought forward by early weaning at week 2, both message and protein did not exhibit increased accumulation after delayed weaning at week 6, and remained at the low level of the new born animal. Treatment of 1‐week‐old and 2‐week‐old animals with triiodothyronine or of 3‐week‐old animals with propylthiouracyl, an antithyroid factor, did not modify the normal pattern of developmental expression of genes CYP1A1, CYP1A2 and CYP3A6. It is concluded that (a) the onset of CYP3A6 gene expression in the fetus occurs at day 30 of gestation, (b) expression of this gene may be induced transplacentally by rifampicin, (c) CYP1A1, CYP1A2 and CYP3A6 gene expression is sharply activated at weaning, and (d) thyroid hormones appear not to be responsible for the pattern of developmental expression of these genes in the rabbit.
Interactions between phosphorylase kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38) and calmodulin were studied with pure preparations of muscle phosphorylase kinase, and with crude ...extracts from muscles of control (C57 Black) and deficient (ICR/IAn) mice, which lack muscle phosphorylase kinase activity. Calmodulin was determined by its ability to stimulate a calmodulin-dependent phosphodiesterase. The amount of calmodulin bound to phosphorylase kinase in muscle extract was estimated to a maximum of 30% of the total amount of calmodulin. In the muscle of the deficient strain a decrease of 35% in the total amount of calmodulin was observed. This correlates with the absence of the calmodulin fraction specifically bound to phosphorylase kinase. From sucrose gradient studies we demonstrated that in the presence of Ca2+ the amount of calmodulin bound to phosphorylase kinase was enhanced, compared to the control in the presence of EGTA. This observation was made both in crude extracts and in pure phosphorylase kinase preparations. Sucrose gradient also showed that muscle phosphorylase kinase can be dissociated to low molecular species when extracts are made in the presence of Ca+; this dissociation was found to be related to a Ca2+-dependent proteolytic effect.
Developmental expression of
CYP1A1, CYP1A2
and
CYP3A6
in the rabbit have been studied. Cytochromes
P
450IA1,
P
450IA2 and
P
450IIIA6 exhibited comparable patterns of developmental expression. Present ...at low level (< 0.05 nmol/mg) in the new born animal up to week 3, these proteins sharply accumulated between weeks 3 and 4 to reach a maximum by week 4 (
P
450IA1, 0.2 nmol/mg;
P
450IA2, 0.8 nmol/mg;
P
450IIIA6, 0.12 nmol/mg) and decreased in the adult (
P
450IA1, 0.2 nmol/mg;
P
450IA2, 0.4 nmol/mg;
P
450IIIA6, 0.09 nmol/mg). Cytochromes
P
450IA1 and
P
450IA2 were not expressed in the untreated fetus. Onset of
CYP3A6
gene expression occurred at day 30 of gestation and both transcription and mRNA accumulation were transplacentally inducible by rifampicin only shortly before birth, i.e. after treatment of the females between days 28 and 30 of gestation. Both long (1.85 kb) and short (1.7 kb) mRNA transcripts were expressed in untreated or rifampicin‐treated fetuses.
CYP3A6
gene expression was also induced by rifampicin in 1‐week‐old and 2‐week‐old animals. Developmental expression of
CYP1A1
and
CYP1A2
genes was shown to be closely related to the diet change accompanying weaning which occurs at weeks 3–4. In animals subjected to either delayed (week 6) or early (week 2) weaning, sharp accumulation of messages, proteins and related activities were delayed or anticipated accordingly with respect to normal weaning. Artificially scheduled weaning gave similar results when repeated with biological‐grade lucern (grown in the absence of chemical fertilizers, pesticides, etc.), the main constituent of commercial rabbit chow. While
CYP3A6
gene expression could be brought forward by early weaning at week 2, both message and protein did not exhibit increased accumulation after delayed weaning at week 6, and remained at the low level of the new born animal. Treatment of 1‐week‐old and 2‐week‐old animals with triiodothyronine or of 3‐week‐old animals with propylthiouracyl, an antithyroid factor, did not modify the normal pattern of developmental expression of genes
CYP1A1, CYP1A2
and
CYP3A6.
It is concluded that (a) the onset of
CYP3A6
gene expression in the fetus occurs at day 30 of gestation, (b) expression of this gene may be induced transplacentally by rifampicin, (c)
CYP1A1, CYP1A2
and
CYP3A6
gene expression is sharply activated at weaning, and (d) thyroid hormones appear not to be responsible for the pattern of developmental expression of these genes in the rabbit.
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