2004 Fiscal Year Final Research Report Summary
Investigation of mechanism on radiation-induced atheroma
| Project/Area Number |
15591997
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pathobiological dentistry/Dental radiology
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| Research Institution | NAGASAKI UNIVERSITY |
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Principal Investigator |
KATAYAMA Ikuo NAGASAKI UNIVERSITY, HOSPITAL OF MEDICINE AND DENTISTRY, INSTRUCTOR, 医学部・歯学部附属病院, 助手 (80295089)
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| Co-Investigator(Kenkyū-buntansha) |
HOTOKEZAKA Yuka NAGASAKI UNIVERSITY, HOSPITAL OF MEDICINE AND DENTISTRY, INSTRUCTOR, 医学部・歯学部附属病院, 助手 (10244089)
YAMAMOTO Kazuo NAGASAKI UNIVERSITY, GRADUATE SCHOOL OF BIOMEDICAL SCIENCE, ASSOCIATE PROFESSOR, 大学院・医歯薬学総合研究科, 助教授 (70255123)
MATSUYAMA Toshifumi NAGASAKI UNIVERSITY, GRADUATE SCHOOL OF BIOMEDICAL SCIENCE, PROFESSOR, 大学院・医歯薬学総合研究科, 教授 (30165922)
NAKAMURA Takashi NAGASAKI UNIVERSITY, GRADUATE SCHOOL OF BIOMEDICAL SCIENCE, PROFESSOR, 大学院・医歯薬学総合研究科, 教授 (30172406)
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| Project Period (FY) |
2003 – 2004
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| Keywords | ionizing radiation / atherosclerosis / macrophage / PPARγ |
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| Research Abstract |
Radiation therapy in cancer patients may results in atherosclerosis of involved large arteries, and the lesion contains a large number of peroxisome proliferator activated receptor γ(PPARγ)-positive macrophages. PPARγ regurates adipogenesis in fibroblasts, monocyte/macrophage differentiation and activation, and apoptosis. Here we demonstrated that ionizing radiation(IR) increased cholesterol uptake by human monocyic U 937 cells, through the mechanism involving CD 36 scavenger receptors. The cholesterol uptake by U 937 cells was associated with enhanced nuclear accumulation of PPARγ, but not PPARα, and activated PPARγ-dependent transcriptional activity. However, PPARγ agonist troglitazone inhibited the IR-induced cholesterol uptake in U 937 cells. Importantly, PPARγ ablation by siRNA enhanced cholesterol uptake in U 937 cells, and troglitazone treatment did not inhibited the uptake in the PPARγ-depleted U 937 cells. In response to IR, human monocytes also showed PPARγ accumulation and cholesterol uptake. These results suggests that PPARγ plays an inhibitory role in the formation of atherosclerosis in response to IR and may provide a possible strategy for prevention of atherosclerosis in cancer patients treated with IR.
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