| 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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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1995: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Keywords | Cytochrome P450 (11beta) / Adrenal cortex / Zona glomerulosa / Notch-Delta / Cytodifferentiation / Hypertension / チトクロムP450 / アルドステロン合成酵素 / ステロイド11-水酸化酵素 / 自然発症高血圧ラット / 本態性高血圧症 |
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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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