Immunohistochemical localization of cytochrome P-450 in rat brain

Kapitulnik, Jaime; Gelboin, H V; Guengerich, F. Peter; Dm, Jacobowitz

doi:10.1016/0306-4522(87)90243-0

Cited by 87 publications

(23 citation statements)

References 16 publications

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“…This observation is consistent with a report of Morse and coworkers showing induction of CYP1A1 and EROD in homogenates of meninges and choroid plexus from BNF-treated rats (Morse et al, 1998). No expression of CYP1A1 in EC of noninduced animals has been noted in previous immunohistochemical studies (Kapitulnik et al, 1987;Warner et al, 1988;Riedl et al, 1996). Based on these observations, we conclude that EC in veins in the leptomeninges and capillaries in the choroid plexus of rodents express a constitutively low but highly inducible and catalytically active CYP1A1 enzyme.…”

Section: Discussionsupporting

confidence: 93%

CYP1A1 and CYP1B1 in Blood-Brain Interfaces: CYP1A1-Dependent Bioactivation of 7,12-Dimethylbenz(a)anthracene in Endothelial Cells

Granberg¹,

Östergren²,

Brandt³

et al. 2003

Drug Metabolism and Disposition

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Section: Discussionsupporting

confidence: 93%

CYP1A1 and CYP1B1 in Blood-Brain Interfaces: CYP1A1-Dependent Bioactivation of 7,12-Dimethylbenz(a)anthracene in Endothelial Cells

Granberg¹,

Östergren²,

Brandt³

et al. 2003

Drug Metabolism and Disposition

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“…The conservation of other unique features between hct-1 and CYP7 (see below), however, argues for a close relationship, and hct-1 has been designated "CYP7B" (Cyp7b in mouse) by the Committee on Standardized Cytochrome P450 Nomenclature. 3 From the hct-1 leader sequence we surmise that the hct-1 polypeptide resides, like CYP7, in the endoplasmic reticulum and not in mitochondria, the other principal cellular site of CYP activity. The strictly conserved heme binding site motif FXXGXXXCXG(XXXA) (1) is present in hct-1 (residues 440 -453) while the postulated "steroidogenic domain" (e.g.…”

Section: Discussionmentioning

confidence: 99%

A Novel Cytochrome P450 Expressed Primarily in Brain

Stapleton

Steel

Richardson

et al. 1995

Journal of Biological Chemistry

143

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hct-1 (hippocampal transcript) was detected in a differential screen of a rat hippocampal cDNA library. Expression of hct-1 was enriched in the formation but was also detected in rat liver and kidney, though at much lower levels; expression was barely detectable in testis, ovary, and adrenal. In liver, unlike brain, expression was sexually dimorphic; hepatic expression was greatly reduced in female rats. In mouse, brain expression was widespread, with the highest levels being detected in corpus callosum; only low levels were detected in liver. Sequence analysis of rat and mouse hct-1 cDNAs revealed extensive homologies with cytochrome P450s (CYPs), a diverse family of heme-binding monooxygenases that metabolize a range of substrates including steroids, fatty acids, and xenobiotics. Among the CYPs, hct-1 is most similar (39% at the amino acid sequence) to cholesterol 7␣-hydroxylase (CYP7) and contains a postulated steroidogenic domain present in other steroidmetabolizing CYPs but clearly represents a type of CYP not previously reported. Genomic Southern analysis suggests that a single gene corresponding to hct-1 is present in mouse, rat, and human. hct-1 is unusual in that, unlike all other CYPs described, the primary site of expression is in the brain. Similarity to CYP7 and other steroid-metabolizing CYPs may argue that hct-1 (CYP7B) plays a role in steroid metabolism in brain, notable because of the documented ability of brain-derived steroids (neurosteroids) to modulate cognitive function in vivo.Cytochromes P450, a diverse group of heme-containing monooxygenases (termed CYPs) 1 (for nomenclature see Nelson et al. (1)), catalyze a variety of oxidative conversions, notably of steroids but also of fatty acids and xenobiotics. Though most abundantly expressed in the testis, ovary, placenta, adrenal, and liver, the brain is a further site of CYP expression (2-6).Several CYP activities or mRNAs have been reported in the nervous system, predominantly of types metabolizing fatty acids and xenobiotics (subclasses CYP2C, -2D, -2E, and -4 (6, 7)). However, primary rat brain-derived glial cells can synthesize pregnenolone and progesterone in vitro (8). Mellon and Deschepper (9) provided molecular evidence for the presence, in brain, of key steroidogenic enzymes CYP11A1 (scc) and CYP11B1 (11␤) but failed to detect CYP17 (c17) or CYP11B2 (AS). Though CYP21A1 (c21) activity is reported to be present in brain (10) authentic CYP21A1 transcripts were not detected (11).Interest in brain steroid metabolism has been fueled by the finding that adrenal-and brain-derived steroids (neurosteroids) can modulate cognitive function and synaptic plasticity (reviewed in Refs. 12-17). For instance, pregnenolone and steroids derived from it are reported to have memory-enhancing effects in mice (18,19). However, the full spectrum of brain CYPs and the biological roles of their metabolites in vivo have not been established.To investigate such regulation of brain function our studies have focused on the hippocampus, a brain region important ...

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“…For example, some studies of CYP1A1 protein by western blot analysis detected the enzyme in the cerebellum but not in cerebral cortex of b-naphthoflavone (b-NF)-treated rats (Warner et al 1988), whereas other studies using immunohistochemistry were able to detect immunoreactivity in the hypothalamus, but not in the cerebral cortex or cerebellum, of 3-methylcholanthrene-treated rats (Kapitulnik et al 1987). The antibody against CYP1A1 used in these studies also recognized CYP1A2, hence the immunoreactivity detected did not distinguish between the two enzymes.…”

Section: Introductionmentioning

confidence: 96%

Constitutive and inducible levels of CYP1A1 and CYP1A2 in rat cerebral cortex and cerebellum

Iba

Storch

Ghosal

et al. 2003

Archives of Toxicology

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We examined the constitutive and inducible levels of microsomal cytochromes P450 1A1 and 1A2 (CYP1A) in rat cerebral cortex and cerebellum at the level of proteins by western blot analysis, and by catalytic activities via ethoxyresorufin O-deethylase (EROD) and methoxyresorufin O-demethylase (MROD). In the cerebral cortex, cytochrome P450 1A1 (CYP1A1) protein was more abundant than cytochrome P450 1A2 (CYP1A2) protein. Treatment with beta-naphthoflavone (beta-NF) caused a slight decrease in the level of the former but induced the latter 5.8-fold. In the cerebellum, in contrast to the cerebral cortex, CYP1A1 protein was less abundant than CYP1A2 protein in untreated rats, and while beta-NF treatment caused a 3.3-fold induction of CYP1A1 protein, it resulted in a 10-fold decrease in CYP1A2 protein. The CYP1A-preferential activity EROD was 2.3-fold higher in the cerebellum than in the cerebral cortex, and was induced 1.5-fold and 1.9-fold in the cerebellum and cerebral cortex, respectively, by beta-NF treatment. The CYP1A2-preferential activity MROD was 3-fold higher in the cerebellum than in the cerebral cortex, and was repressed 2.2-fold in the cerebellum but induced 3.7-fold in the cerebral cortex following beta-NF treatment. The results show that CYP1A1 and CYP1A2 proteins and catalytic activities are constitutively expressed in brain but are differentially inducible in the rat cerebral cortex and cerebellum.

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Immunohistochemical localization of cytochrome P-450 in rat brain

Cited by 87 publications

References 16 publications

CYP1A1 and CYP1B1 in Blood-Brain Interfaces: CYP1A1-Dependent Bioactivation of 7,12-Dimethylbenz(a)anthracene in Endothelial Cells

CYP1A1 and CYP1B1 in Blood-Brain Interfaces: CYP1A1-Dependent Bioactivation of 7,12-Dimethylbenz(a)anthracene in Endothelial Cells

A Novel Cytochrome P450 Expressed Primarily in Brain

Constitutive and inducible levels of CYP1A1 and CYP1A2 in rat cerebral cortex and cerebellum

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