Cell-specific induction of mouse Cyp1a1 mRNA during development.

Dey, Anup; Westphal, Heiner; Nebert, Daniel W.

doi:10.1073/pnas.86.19.7446

Cited by 34 publications

(15 citation statements)

References 29 publications

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“…The homogeneous distribution of CYPlAl in the developing rabbit liver after MC treatment is consistent with the distribution reported for CYPlAl mRNA in the developing mouse liver, from 12.5 days of gestation after MC treatment, as determined by in situ hybridization (49). Developmentally, inducibility of CYPlAl mRNA in the mouse is reported to occur at least 2 weeks earlier in gestation than that of CYPlA2, which occurs near the time of birth ( 5 ) .…”

Section: Discussionsupporting

confidence: 69%

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

Rich

Foster²,

Edwards³

et al. 1993

J Histochem Cytochem.

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We investigated the expression, distribution, and inducibility of 3-methylcholanthrene (MC)-inducible P450 enzymes, CYPlAl and 1A2, in livers of rabbits at different stages of development, ranging from 4 days before birth (-4 days of age) to adulthood. These enzymes were identified by immunoblotting and immunocytochemistry and quantified by dot-blotting, utilizing previously characterized monoclonal antibodies, 107 and 31412, specific for CYPIA2 and both CYPlAl and 1A2, respectively, and a polydonal antibody that recognizes both enzymes. Expression of CYPIA2 is always greater than that of CYPlAl in livers of untreated rabbits, regardless of age. Moreover, immunocytochemistry showed that CYPlAl is evenly distributed throughout the liver at all ages, whereas CYPIA2 is highly localized to only a few scattered cells at 1 day before birth. More hepatocytes express this enzyme perinatally. By 6 days of age, expression of CYPIA2 is confined to a narrow band of centrilobular ceb, but with increasing age the enzyme is expressed in more hepatocytes until weaning, when all hepatocytes are posi-

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Section: Discussionsupporting

confidence: 69%

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

Rich

Foster²,

Edwards³

et al. 1993

J Histochem Cytochem.

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“…However, total CYP content in different regions of human brain has been recently published (Bhambre et al, 1992), and monooxygenase activities associated with various CYP have been described in different regions of human brain (Ravindranath et al, 1989a). CYP1A1 mRNA levels appear to correlate well with the presence of functional CYP1A1 enzyme activity (Gonzalez, 1989;Jaiswal et al, 1985;Dey et al, 1989). In this respect, our results indicating higher basal expression levels of CYP1A1 mRNA in the cerebellum and frontal lobe, compared to the liver, are in good agreement with Bhambre et al (1992), who reported that mean ethoxycoumarin O-deethylase activities from the frontal cortex and cerebellar tissue were more than twofold higher to that in the liver.…”

Section: Discussionmentioning

confidence: 96%

Regiospecific expression of cytochrome P‐450s and microsomal epoxide hydrolase in human brain tissue

Farin

Omiecinski

1993

Journal of Toxicology and Environmental Health

118

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The central nervous system is an important potential target for certain environmental protoxins, but relatively little is known regarding brain-specific expression of biotransformation enzyme systems. We undertook the present study to identify regional and cellular expression patterns of individual cytochrome P-450 genes (CYP) and microsomal epoxide hydrolase (mEH) in human brain. Various regions of normal human brain were isolated and examined with respect to mRNA levels of CYP1A1, CYP1A2, CYP2E1, CPY3A, and mEH, using specific oligomer probes and reverse transcriptase-coupled polymerase chain reaction analysis. We also used immunohistochemical techniques, with antipeptide-derived antibodies, to identify specific cells from various regions of the human brain producing CYP1A1 and mEH protein. Relatively equivalent mRNA expression levels of mEH were detected in the cerebellum (C), frontal (F), occipital (O), pons (P), red nucleus (RN), and substantia nigra (SN) regions of brain. The mRNA expression patterns of CYP2E1 and CYP1A2 were similar; although detected in all brain regions examined, the RN and SN exhibited lower levels of CYP2E1 and CYP1A2 mRNA expression compared to other regions. In addition, regional differences in CYP3A and CYP1A1 mRNA expression also were observed, with the highest level of CYP3A mRNA present in the P region compared to the C, F, O, and RN, while no CYP3A mRNA was detected in the SN. CYP1A1 mRNA expression was evident in all brain regions, but the levels of CYP1A1 mRNA in the P and RN were lower than in the C, F, O, and SN. In all cases, the regional mRNA expression levels of these CYP and mEH mRNAs were less than the corresponding levels detected from the same individual's liver. CYP1A1 and mEH immunoreactivity was present in most neurons of the SN, RN, P, median raphae, locus ceruleus, inferior vestibular nucleus, dorsal motor nucleus of the vagus, and thalamus. Some but not all astrocytes within these regions also demonstrated 1A1 and mEH immunoreactivity. These results indicate that many neurons and astrocytes express mEH and CYP1A1 as well as other CYP genes, and suggest that localized biotransformation events within the certain central nervous system may account for toxicities initiated by exposure to certain environmental chemicals.

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“…These data correlate well with the results from Northern blotting studies in which mRNA to both 1A1 and 1A2 is detected from as early as 2 weeks or a few days prior to parturition, respectively (Giachelli and Omiecinski, 1987;Kimura et al, 1986Kimura et al, , 1987. By using antisense probes from 3Ј-specific regions of the Cyp1-a1 and Cyp1-a2 genes, in situ hybridisation studies have revealed that mRNA to 1-a1 is localised in all hepatocytes of the developing foetal mouse liver from as early as 12.5 days of gestation, but only after MC treatment (Dey et al, 1989). Yang et al (1991) also demonstrated the inducibility of the CYP1A1 gene from as early as 10 days of gestation, emphasising the potential role these enzymes may have in activating teratogenic agents to their more reactive species during critical stages of organogenesis.…”

Section: Expression and Inducibility Of P450 Enzymes In Mouse Rat Amentioning

confidence: 99%

Expression and inducibility of P450 enzymes during liver ontogeny

Rich

Boobis

1997

Microsc. Res. Tech.

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Cell-specific induction of mouse Cyp1a1 mRNA during development.

Abstract: The dioxin-inducible cytochrome P1450

Cited by 34 publications

References 29 publications

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

Ontogenetic development of the distribution of constitutive and 3-methylcholanthrene-induced CYP1A1 and CYP1A2 in rabbit liver.

Regiospecific expression of cytochrome P‐450s and microsomal epoxide hydrolase in human brain tissue

Expression and inducibility of P450 enzymes during liver ontogeny

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