1997 Fiscal Year Final Research Report Summary
Hypertensinogenic Gene in Adrenal Cortex
| Project/Area Number |
07457039
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Osaka University |
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Principal Investigator |
OKAMOTO Mitsuhiro Osaka University Medical School, Professor, 医学部, 教授 (90028613)
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| Project Period (FY) |
1995 – 1997
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| Keywords | Cytochrome P450 (11beta) / Adrenal cortex / Zona glomerulosa / Notch-Delta / Cytodifferentiation / Hypertension |
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| Research Abstract |
(1) Performing the PCR-SSCP analysis on the Exons 5 and 6 of human CYP11B1 gene, we found that nucleotide substitutions occurred with high frequency at codons for A291 (exon 5), L362 (exon 6) and R366 (exon 6). There seemed to be no correlationship between these nucleotide substitutions and pathogenesis of hypertension.
(2) Dahl's salt-sensitive hypertensive (DS) and salt-resistant normotensive (DR) rats are genetic strains well-studied for pathogenesis of hypertension. We previously reported that DR rats contained five aminoacid alterations in their CYP11B1. The mutated enzyme had lower steroid 18-hydroxylation activity than the wild type enzyme. Site-directed mutagenesis was introduced to the enzyme to exlore functional roles playd by the mutated amino acids. The results suggested that two of the five mutations, V381L and I384L,were responsible for the abnormal 18-hydroxylation activity. It is possible that the mutation in DR's CYP11B1 causes a lower plasma level of 18 (OH) DOC,which may in turn repress pathogenesis of hypertension in this rat.
(3) We isolated and characterized a gene that is specifically expressed in the zona glomerulosa cells in rat adrenal cortex. This gene may have a function to control the development and differentiation of adrenal cortex.
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[Publications] Okamoto, M., Nonaka, Y., Ohta, M., Takemori, H., Halder, S.K., Wang, Z., Sun, T., Hatano, O., Takakusu, A., and Murakami, T.: "Cytochrome P450(11beta) : Structure-function relationship of the enzyme and its involvement in the blood pressure regulation." J.Steroid Biochem.Mol.Biol.53. 89-94 (1995)
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[Publications] Nonaka, Y., Takemori, H., Halder, S.K., Sun, T., Ohta, M., Hatano, O., Takakusu, A., and Okamoto, M.: "Frog cytochrome P450 (11beta, aldo), a single enzyme involved in the final steps of glucocorticoid and mineralocorticoid biosynthesis." Eur.J.Biochem.229. 249-256 (1995)
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[Publications] Takemori, H., Halder, S.K., Nonaka, Y., Fujii, T., Ohta, M., Hatano, O., and Okamoto, M.: "Polyadenylation-mediated translational regulation of maternal P450 (11beta) mRNA in frog oocytes." Eur.J.Biochem.250. 197-204 (1997)
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[Publications] Takemori, H., Zolotaryov, F.N., Ting, L., Urbain, T., Komatsubara, T., Hatano, O., Okamoto, M., and Tojo, H.: "Identification of functional domains of rat intestinal phopspholipase B/lipase. Its cDNA cloning, expression, and tissue distribution." J.Biol.Chem.273. 2222-2231 (1998)
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[Publications] Okamoto, M., Nonaka, Y., Ishii, S., Takemori, H., Wang, Z., Takami, S., Higaki, J., Miki, T., and Ogihara, T.: Steroid 11beta-hydroxylase/aldosterone synythase and its role in blood pressure regulation. in Adrenal glands, Vascular System and Hypertension.(ed.Vinson, G.P.and Anderson, D.C.) J.Endocrinol.Ltd, Bristol, UK., 187-194 (1996)
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