| Project/Area Number |
07557015
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 試験 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SHIBAHARA Shigeki Tohoku University School of Medicine, Professor, 医学部, 教授 (70206142)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Kenichi Tohoku University School of Medicime, Assistant Professor, 医学部, 助手 (90241629)
TAKAHASHI Kazuhiro Tohoku University School of Medicine, Lecturer, 医学部, 講師 (80241628)
SHIBATA Koushi Pola R & D Laboratories, Dermal Research Department, Staff Investigator, 医薬品研究所, 副主任研究員
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥8,500,000 (Direct Cost: ¥8,500,000)
Fiscal Year 1996: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1995: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | transcription factor / melanin biosynthesis / heme catabolism / tyrosinase / heme oxygenase / cell differentiation / MITF |
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| Research Abstract |
We have successfully developed a new luciferase assay technology that enables the expression of pigment cells, transfected with the fusion gene containing the firefly luciferase gene, to be captured on photographic images. The light discharged by the luciferase-mediated reaction can be quantified by chemical luminescence measurement. Using the photocounting camera and an efficient transfection method, we were able to detect the promoter activity of the tyrosinase gene in human melanocytes. Furthermore, we have obtained the following results as summarized below. 1. The three cis-regulatory elements of the human tyrosinase gene have been identified, and each of these elements contains one copy of a CATGTG motif. We showed that each CATGTG motif is required for pigment cell-specific transcription. 2. In the course of studying the regulation of the heme oxygenase-1 gene expression during macrophage differentiation, we showed the presence of a putative silencer sequence, repressing a function of the heat shock element, which is located in the 5^1-flanking region of the human heme oxygenase-1 gene. 3. Three types of nitric oxide (NO) donors increased the expression levels of heme oxygenase-1 mRNA,suggesting a possible coordinated regulation of heme oxygenase-1 and NO synthase mRNAs. 4. Both heme oxygenase-1 and inducible NO synthase mRNAs were overexpressed in human primary brain tumors compared to the normal brain tissues. 5. The choroid plexus probuces cerebrospinal fluid which plays an important role not only in the mechanical support of the brain but also in the chemical homeostasis of the brain. We found that adrenomedullin, a potent vasodilator peptide, is produced and secreted by cultured choroid plexus carcinoma cells, a rare neoplasm derived from the epithelium of the choroid plexus.
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