Molecular identity and gene expression of aldosterone synthase cytochrome P450
Abstract
11{beta}-Hydroxylase (CYP11B1) of bovine adrenal cortex produced corticosterone as well as aldosterone from 11-deoxycorticosterone in the presence of the mitochondrial P450 electron transport system. CYP11B1s of pig, sheep, and bullfrog, when expressed in COS-7 cells, also performed corticosterone and aldosterone production. Since these CYP11B1s are present in the zonae fasciculata and reticularis as well as in the zona glomerulosa, the zonal differentiation of steroid production may occur by the action of still-unidentified factor(s) on the enzyme-catalyzed successive oxygenations at C11- and C18-positions of steroid. In contrast, two cDNAs, one encoding 11{beta}-hydroxylase and the other encoding aldosterone synthase (CYP11B2), were isolated from rat, mouse, hamster, guinea pig, and human adrenals. The expression of CYP11B1 gene was regulated by cyclic AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion-signaling as well as cAMP-signaling. Salt-inducible protein kinase, a cAMP-induced novel protein kinase, was one of the regulators of CYP11B2 gene expression.
- Authors:
- Laboratories for Biomolecular Networks, Graduate School of Frontier Biosciences, Osaka University, 1-3 Yamadaoka, Suita, Osaka 565-0871 (Japan) and Department of Molecular Physiological Chemistry, Graduate School of Medicine (H-1), Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan). E-mail: mokamoto@mr-mbio.med.osaka-u.ac.jp
- College of Nutrition, Koshien University, Takarazuka, Hyogo 665-0006 (Japan)
- Department of Molecular Physiological Chemistry, Graduate School of Medicine (H-1), Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
- Department of Food and Nutrition, Faculty of Human Life Sciences, Senri Kinran University, Suita, Osaka 565-0873 (Japan)
- Publication Date:
- OSTI Identifier:
- 20793199
- Resource Type:
- Journal Article
- Resource Relation:
- Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 338; Journal Issue: 1; Other Information: DOI: 10.1016/j.bbrc.2005.07.187; PII: S0006-291X(05)01690-6; Copyright (c) 2005 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; ALDOSTERONE; AMP; CALCIUM IONS; CARBON 11; CARBON 18; CATTLE; CORTICOSTERONE; GENES; GUINEA PIGS; HAMSTERS; HYDROXYLASES; MICE; RATS; SHEEP; SWINE
Citation Formats
Okamoto, Mitsuhiro, Nonaka, Yasuki, Takemori, Hiroshi, and Doi, Junko. Molecular identity and gene expression of aldosterone synthase cytochrome P450. United States: N. p., 2005.
Web. doi:10.1016/J.BBRC.2005.0.
Okamoto, Mitsuhiro, Nonaka, Yasuki, Takemori, Hiroshi, & Doi, Junko. Molecular identity and gene expression of aldosterone synthase cytochrome P450. United States. doi:10.1016/J.BBRC.2005.0.
Okamoto, Mitsuhiro, Nonaka, Yasuki, Takemori, Hiroshi, and Doi, Junko. Fri .
"Molecular identity and gene expression of aldosterone synthase cytochrome P450". United States.
doi:10.1016/J.BBRC.2005.0.
@article{osti_20793199,
title = {Molecular identity and gene expression of aldosterone synthase cytochrome P450},
author = {Okamoto, Mitsuhiro and Nonaka, Yasuki and Takemori, Hiroshi and Doi, Junko},
abstractNote = {11{beta}-Hydroxylase (CYP11B1) of bovine adrenal cortex produced corticosterone as well as aldosterone from 11-deoxycorticosterone in the presence of the mitochondrial P450 electron transport system. CYP11B1s of pig, sheep, and bullfrog, when expressed in COS-7 cells, also performed corticosterone and aldosterone production. Since these CYP11B1s are present in the zonae fasciculata and reticularis as well as in the zona glomerulosa, the zonal differentiation of steroid production may occur by the action of still-unidentified factor(s) on the enzyme-catalyzed successive oxygenations at C11- and C18-positions of steroid. In contrast, two cDNAs, one encoding 11{beta}-hydroxylase and the other encoding aldosterone synthase (CYP11B2), were isolated from rat, mouse, hamster, guinea pig, and human adrenals. The expression of CYP11B1 gene was regulated by cyclic AMP (cAMP)-dependent signaling, whereas that of CYP11B2 gene by calcium ion-signaling as well as cAMP-signaling. Salt-inducible protein kinase, a cAMP-induced novel protein kinase, was one of the regulators of CYP11B2 gene expression.},
doi = {10.1016/J.BBRC.2005.0},
journal = {Biochemical and Biophysical Research Communications},
number = 1,
volume = 338,
place = {United States},
year = {Fri Dec 09 00:00:00 EST 2005},
month = {Fri Dec 09 00:00:00 EST 2005}
}
-
Both increased cell proliferation and {open_quotes}altered{close_quotes}CYP gene expression are prominent phenomena associated with liver tumor promotion by nongenotoxic carcinogen treatment. BRDU-labeled parenchymal nuclei were observed primarily in the periportal area of groups of rats, independent of nongenotoxic carcinogen treatment. Treatment with each of the 5 nongenotoxic carcinogens resulted in profound alterations in CPY gene expression at both the transcriptional and translational levels. Expression of CYP1A1, 1A1/2, 3A1, 2B1/2, and 4A immunoproteins demonstrated nongenotoxic carcinogen-specific patterns in both magnitude and zonal distribution. In agreement with the CYP immunoprotein data, treatment with each of the five nongenotoxic carcinogens resulted in a uniquemore »
-
The human CYP2F gene subfamily: Identification of a cDNA encoding a new cytochrome P450, cDNA-directed expression, and chromosome mapping
A cDNA coding for a P450, designated IIF1, was isolated from a human lung {lambda}gt11 library by screening with a human IIC9 cDNA probe. The cDNA-encoded IIF1 protein had 491 amino acids and a calculated molecular weight of 55,507. IIF1 cDNA, expressed by using a vaccinia virus vector, produced a cytochrome with a {lambda}{sub max} of 454 nm when reduced and complexed with carbon monoxide. This enzyme was able to dealkylate ethoxycoumarin, propoxycoumarin, and pentoxyresorufin but possessed no activity toward ethoxyresorufin and only trace dearylation activity toward benzyloxyresorufin. A variant cDNA, designated IIF1v, was isolated that was identical with IIF1more » -
DHA down-regulates phenobarbital-induced cytochrome P450 2B1 gene expression in rat primary hepatocytes by attenuating CAR translocation
The constitutive androstane receptor (CAR) plays an important role in regulating the expression of detoxifying enzymes, including cytochrome P450 2B (CYP 2B). Phenobarbital (PB) induction of human CYP 2B6 and mouse CYP 2b10 has been shown to be mediated by CAR. Our previous study showed that PB-induced CYP 2B1 expression in rat primary hepatocytes is down-regulated by both n-6 and n-3 polyunsaturated fatty acids (PUFAs), especially docosahexaenoic acid (DHA); however, the mechanism for this down-regulation by DHA was previously unknown. The objective of the present study was to determine whether change in CAR translocation is involved in the down-regulation bymore » -
The cytochrome P450 2AA gene cluster in zebrafish (Danio rerio): Expression of CYP2AA1 and CYP2AA2 and response to phenobarbital-type inducers
The cytochrome P450 (CYP) 2 gene family is the largest and most diverse CYP gene family in vertebrates. In zebrafish, we have identified 10 genes in a new subfamily, CYP2AA, which does not show orthology to any human or other mammalian CYP genes. Here we report evolutionary and structural relationships of the 10 CYP2AA genes and expression of the first two genes, CYP2AA1 and CYP2AA2. Parsimony reconstruction of the tandem duplication pattern for the CYP2AA cluster suggests that CYP2AA1, CYP2AA2 and CYP2AA3 likely arose in the earlier duplication events and thus are most diverged in function from the other CYP2AAs.more » -
Modes of heme binding and substrate access for cytochrome P450 CYP74A revealed by crystal structures of allene oxide synthase
Cytochrome P450s exist ubiquitously in all organisms and are involved in many biological processes. Allene oxide synthase (AOS) is a P450 enzyme that plays a key role in the biosynthesis of oxylipin jasmonates, which are involved in signal and defense reactions in higher plants. The crystal structures of guayule (Parthenium argentatum) AOS (CYP74A2) and its complex with the substrate analog 13(S)-hydroxyoctadeca-9Z,11E-dienoic acid have been determined. The structures exhibit a classic P450 fold but possess a heme-binding mode with an unusually long heme binding loop and a unique I-helix. The structures also reveal two channels through which substrate and product maymore »