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Title: 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:
 [1];  [2];  [3];  [4]
  1. 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
  2. College of Nutrition, Koshien University, Takarazuka, Hyogo 665-0006 (Japan)
  3. Department of Molecular Physiological Chemistry, Graduate School of Medicine (H-1), Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871 (Japan)
  4. 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 » composition of mRNAs of CYP2B1, 2B2, 2C6, 2C11, 3A1, 3A2, and 4A1, which were variably increased or decreased relative to the untreated control livers, depending on the treatment. Similarly, the rate and pattern of CYP enzyme-mediated hydroxylation toward testosterone, 17{beta}-estradiol, corticosterone, and lauric acid were greatly altered by nongenotoxic carcinogen treatment. Because many endogenous substrates are modulators of DNA and RNA synthesis, intracellular kinetics of endogenous substrates of CYP enzymes in the corresponding hepatocytes could contribute, at least in part, to the differences in gene expression, differentiation, and cell proliferation among the hepatocytes in the cell plate. 64 refs., 11 figs., 2 tabs.« less
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