| Project/Area Number |
08044304
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Kumamoto University |
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Principal Investigator |
HORIUCHI Seikoh Kumamoto University, School of Medicine, Professor, 医学部, 教授 (10117377)
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| Co-Investigator(Kenkyū-buntansha) |
CHANG Ta-Yuan Dartmouth Medical School, Biochemistry, Professor, 医学部, 教授
HAKAMATA Hideki Kumamoto University, School of Medicine, Assistant Professor, 医学部, 助手 (70284750)
MIYAZAKI Akira Kumamoto University, School of Medicine, Associate Professor, 医学部, 講師 (70253721)
CHANG TaーYua ダーツマス大学, 医学部, 教授
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥5,400,000 (Direct Cost: ¥5,400,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1996: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Keywords | cholesterol metabolism / ACAT / macrophage / foam cells / cDNA cloning |
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| Research Abstract |
We prepared a specific antiboty (DM10) against human acyl-conzyme A : cholesterol acyltransnferase (ACAT) and analyzed human tissues by immunohistochemical methods. ACAT was expressed in various human tissues including adrenal cortex, macrophages and their related cells such as Langerhans cells and alveolar macrophages, nervous cells such as Schwann cells and ganglion cells, and sebaceous glands. Under pathological conditions, ACAT was markedly expressed in aortic atherosclerotic lesions particularly in macrophage-derived foam cells, suggesting an important role of ACAT in atherogenesis. Western blotting of cultured human monocytics showed that expression of ACAT protein was markedly increased during monocyte differentiation, which explains, in part, marked expression of ACAT in human atherosclerotic lesions.
We cloned rat ACAT cDNA as a homologue of human ACAT and examined its tissue distribution in rat. Among four tissues examined, ACAT activity was highest in adrenal followed by liver while those of intestine and aorta were low. The level of mRNA was also highest in adrenal. However, in contrast to high ACAT activity, the level of mRNA in liver was extremely low. Immunohistochemical staining with DM10 showed marked expression of ACAT in adrenal but negligible expression in liver. These results suggest the presence of ACAT isozyme in rat liver. Treatment of microsomal fraction of rat adrenal with chemical cross-linkers showed formation of dimer and tetramer of ACAT.Thus, we provided biochemical evidence for oligomerization of ACAT.
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