Disease relevance of Cyp11b3

• The aldosterone synthase activities of the mutants were decreased to varying degrees indicating that point mutations at positions 296, 301, 302, and 335 could potentially cause hypoaldosteronism [1].
• Mouse hepatoma x rat hepatocyte hybrids that segregate rat chromosomes were used to determine the chromosomal location of the rat genes encoding 11 beta-hydroxylase and aldosterone synthase (Cyp11b1 and Cyp11b2 respectively) [2].
• Molecular variants in the P450c11AS gene as determinants of aldosterone synthase activity in the Dahl rat model of hypertension [3].
• Hypoxia in vivo inhibits aldosterone synthesis and aldosterone synthase mRNA in rats [4].
• OBJECTIVE: In consideration of the hypothetical possibility that locally produced aldosterone is likely to take an active part in fibrogenesis of the liver, we undertook the present study to investigate the expression of aldosterone synthase gene CYP11B2 in rat liver and the curative effect of spironolactone on fibrosis of the liver [5].

High impact information on Cyp11b3

• Further genetic studies support a role for antiotensinogen, aldosterone synthase and a region close to the epithelial sodium channel in blood pressure regulation [6].
• Cytochrome P450 aldosterone synthase expression in the adrenal cortex was stimulated by nephrectomy alone and by nephrectomy combined with low salt intake (P < .05), with consequent increases in PA concentrations [7].
• In intact rats, plasma renin activity (PRA) and adrenal renin activity and expression were progressively raised by salt restriction and losartan, whereas aldosterone synthase mRNA and plasma aldosterone (PA) levels were increased by salt restriction and reduced by losartan [7].
• Using the quantitative reverse transcriptase-polymerase chain reaction, the terminal enzymes of corticosterone and aldosterone synthesis (11beta-hydroxylase and aldosterone synthase, respectively) were detected in the rat heart [8].
• A second P450c11 gene (CYP11B2) encodes P450c11AS, which is the aldosterone synthase found solely in the adrenal zona glomerulosa [9].

Biological context of Cyp11b3

• The deduced amino acid sequence contained the regions well conserved among all cytochrome P-450s sequenced to date, and also a portion (residues 25-44) which was identical to the N-terminal peptide sequence of rat aldosterone synthase cytochrome P-450 [10].
• Using an oligonucleotide probe designed on the basis of the N-terminal amino acid sequence of purified rat aldosterone synthase cytochrome P-450 [(1989) J. Biol. Chem. 264, 10935] we have isolated from rat adrenal cDNA library a 2687 base pair cDNA that encodes a protein of 500 amino acid residues [10].
• Molecular biology of rat steroid 11 beta-hydroxylase [P450(11 beta)] and aldosterone synthase [P450(11 beta, aldo)] [11].
• Regulation of aldosterone synthase gene expression in the rat adrenal gland and central nervous system by sodium and angiotensin II [12].
• Microsatellite polymorphism analysis allows the individual assignment of the rat 11 beta-hydroxylase gene (Cyp11b1) and the rat aldosterone synthase gene (Cyp11b2) to chromosome 7 using rat x mouse somatic cell hybrids and identifies differences between and within various rat strains [2].

Anatomical context of Cyp11b3

• Isolation of aldosterone synthase cytochrome P-450 from zona glomerulosa mitochondria of rat adrenal cortex [13].
• Molecular cloning of a cDNA encoding aldosterone synthase cytochrome P-450 in rat adrenal cortex [10].
• In the brain, 11beta-hydroxylase and aldosterone synthase were detected in the cerebellum, especially the Purkinje cells, as well as the hippocampus [14].
• Expression of the zone-specific steroidogenic enzymes, cytochrome P450 aldosterone synthase (P450aldo), and P450 11beta hydroxylase (P45011beta), produced by the zona glomerulosa and zona fasciculata/reticularis, respectively, can be used to define the adrenal cortical cell phenotype of these two zones [15].
• Expression of the mRNA for the aldosterone synthase was demonstrated by RT-PCR/Southern blot in adrenal, aorta, hypothalamus, hippocampus, amygdala, cerebrum, and cerebellum [16].

Associations of Cyp11b3 with chemical compounds

• Aldosterone production, activity of aldosterone synthase, and expression of mRNA for CYP11B2 and AT1 receptor were increased in hearts of rats with high sodium intake [17].
• The adrenocortical enzymes of the steroidogenic late pathway in the rat are aldosterone synthase (P450aldo), which catalyzes the production of aldosterone, and 11 beta-hydroxylase (P45011 beta), which catalyzes the production of corticosterone throughout the cortex [18].
• Regulation of aldosterone synthase cytochrome P450 (CYP11B2) and 11 beta-hydroxylase cytochrome P450 (CYP11B1) expression in rat adrenal zona glomerulosa cells by low sodium diet and angiotensin II receptor antagonists [19].
• I248T, Q43R, and T493M had no effect on steroid production compared to wild-type aldosterone synthase [20].
• To assess their importance in determining the different functional specificities, we substituted aldosterone synthase-specific (aspartate D147, isoleucine I248, glutamine Q43, and threonine T493) with 11beta-hydroxylase-specific amino acids (glutamate E147, threonine T248, arginine R43, and methionine M493), respectively [20].

Other interactions of Cyp11b3

• In vitro, the CYP11B2 (aldosterone synthase) of the glomerulosa can and does utilise as substrates products arising from CYP11B1 (11beta-hydroxylase) activity in fasciculata cells [21].
• These results suggest that testosterone inhibits the basal and ANG II- and ACTH-stimulated release of aldosterone, via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated cAMP accumulation in rat ZG cells [22].
• We measured mRNA expression of aldosterone synthase, mineralocorticoid receptor (MR1), 12-lipoxygenase (12-LO), serum- and glucocorticoid- inducible kinase and K-ras in male rats [23].

Analytical, diagnostic and therapeutic context of Cyp11b3

• Differentiation of the expression of aldosterone synthase and 11 beta-hydroxylase mRNA in the rat adrenal cortex by reverse transcriptase-polymerase chain reaction [18].
• The concentrations of aldosterone synthase gene (CYP11B2) mRNA and angiotensin II receptor (AT1R) mRNA were determined by competitive polymerase chain reaction [24].
• The expression of aldosterone synthase (CYP11B2) and AT(2) receptor mRNA was detected by nonradioactive in situ hybridization [25].
• The effects of aging on the activity of aldosterone synthase and the expression of cytochrome P450 side-chain cleavage enzyme (P450scc) in ZG cells were determined by thin-layer chromatography and Western blot analysis, respectively [26].
• RT-PCR and immunohistochemistry established that neurons express 11beta-hydroxylase and aldosterone synthase mRNAs and protein [27].

References