2007 Fiscal Year Final Research Report Summary
Application study of a novel apoptogenic protein for the pathogenesis of atherosclerotic diseases
| Project/Area Number |
18590810
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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 |
Circulatory organs internal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
YASUDA Osamu Osaka University, Graduate School of Medicine, Assistant Professor (00372615)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUO Keisuke Mukogawa Woman's University, School of Human Environmental Sciences, Professor (40156758)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Atherosclerosis / Apoptosis / Mitochondria / Smooth muscle cell |
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| Research Abstract |
Apop is a protein originally isolated as a factor of unlkown function from cultured atherosclerotic smooth muscle cells. We found recently that expression of Apop induces apoptosis of vascular smooth muscle cells (SMC) in culture by releasing cytochrome c from mitochondria. Release of cytochrome c from the permeability transition pore (PTP) is believed to play an important role in ischemia/reeoxygenation-induced cardiomyocyte apoptosis, which contributes the development of heart failure following balloon angioplasty after myocardial infarction. This study was performed to investigate the role of Apop in hypoxia/reoxygenation-induced death of cardiomyocytes. Neonatal cardiomyccybas were prepared from ventricles of 2- to 3-day-old Sprague-Dawley rats and maintained in DMEM supplemented with 10% fetal bovine serum. Antisense plasmid to prevent Apop expression or control vector was introduced into cardiomyocybes using an electroporator. Cells were then incubated in hypoxic condition (1% O2
… More
) for 48 hours followed by 2 hours of reoxygenation. Cell viability was assessed by MTT assay. Anti-apoptotic bcl-2 family proteins, such as bcl-2 and bcl-xL were unable to prevent Apop-induced apoptosis, while it was prevented by inhibitors of cyclophilin D, an important component of PTP. These findings indicate that the apoptosis induced by Apop is not mediated by bcl-2 family-related channels, but may require PIP on mitochondrial membrane. Introduction of siRNA targeted toward Apop transcript into cultured cells almost completely abolished the green fluorescence of Apop-GFP fusion protein, indicating that siRNA prevents the expression of Apop. The inhibitory activity of siRNA was also confirmed by Western blot analysis. In the experiments of hypoxia/reoxygenation-induced cell death, introduction of siRNA inhibited the activation of caspase-cascade and the death of cultured cardiomyccytes, whereas introduction of control siRNA affected neither caspase activity nor viability; Inhibition of Apop expression prevented hypoxia/reoxygenation-induced death of cardiomyocytes, suggesting that Apop protein may play roles in the development of cardiac diseases following ischemia-reperfusion injury. Less
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Research Products
(34 results)
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[Journal Article] Potential Role of CYLD (Cylindromatosis) as a Deubiquitinating Enzyme in Vascular Cells2008
Author(s)
Takami, Y, Nakagami, H, Morishita, R, Katsuya, T, Hayashi, H, Mori, M, Koriyama, H, Baba, Y, Yasuda, O, Rakugi, H, Ogihara, T, Kaneda, Y
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Journal Title
American journal of pathology 172(3)
Pages: 818-829
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Different changes of bone mineral density and the nutritional status after hospitalization between vascular dementia and Alzheimer's disease in elderly female patients2007
Author(s)
Suzuki, A, Fukuo, Osamu, Yasuda, Kazuhisa, Taniguchi, Shoichi, Kitano, Toshio, Ogihara
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Journal Title
Geriatrics and Gerontology International 7
Pages: 363-370
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Ubiquitin carboxyl-terminal hydrolase Ll, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation2007
Author(s)
Takami, Y, Nakagami, H, Morishita, R, Katsuya, T, Cui, TX, Ichikawa, T, Saito, Y, Hayashi, H, Kikuchi, Y, Nishikawa, T, Baba, Y, Yasuda, Rakugi, H, Ogihara, T, Kaneda, Y
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Journal Title
Arteriosclerosis, thrombosis, and vascular biology 27(10)
Pages: 2184-2190
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Aspirin prevents adhesion of T lymphoblasts to vascular smooth muscle cells.2007
Author(s)
Yotsui, T, Yasuda, O, Kawamoto, H, Higuchi, M, Chihara, Y, Umemoto, E, Tanaka, T, Miyasaka, M, Rakugi, H, Ogihara, T
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Journal Title
FEBS letters 581(3)
Pages: 427-432
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tissue inhibitor of metalloproteinase-3 deficiency inhibits blood pressure elevation and myocardial microvascular remodeling induced by chronic administration of Nomega-nitro-L-arginine methyl ester in mice2007
Author(s)
Higuchi, M, Yasuda, O, Kawamoto, H, Yotsui, T, Baba, Y, Ozaki, T, Maeda, N, Fukuo, K, Rakugi, H, Ogihara, T
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Journal Title
Hypertension Research 30(6)
Pages: 563-571
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apop-1, a novel protein inducing cyclophilin D-dependent but Bax/Bak-related channel-independent apoptosis2006
Author(s)
Yasuda, O, Fukuo, K, Sun, X, Nishitani, M, Yotsui, T, Higuchi, M, Suzuki, T, Rakugi, H, Smithies, O, Maeda, N, Ogihara, T
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Journal Title
Journal of Biological Chemistry 281(33)
Pages: 23899-23907
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction2006
Author(s)
Kawamoto, H, Yasuda, 0, Suzuki, T, Ozaki, T, Yotsui, T, Higuchi, M, Rakugi, H, Fukuo, K., Ogihara, T., Maeda, N
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Journal Title
Hypertension Research 29(4)
Pages: 285-294
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Fas ligand mRNA levels of circulating leukocytes reflect endothelial dysfunction in hyperlipidemic but not in non-hyperlipidemic patients2006
Author(s)
Related, Articles, LinksKotani, N, Fukuo, K, Yasuda, O, Sugimoto, K, Katuya, T, Takemura, Y, Kawamoto, H, Yokoi, T, Suzuki, A, Ogihara T
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Journal Title
Hypertension Research 29(4)
Pages: 217-225
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Apoptosis Signal-Regulating Kinase 1 Mediates Cellular Senescence Induced by High Glucose in Endothelial Cells2006
Author(s)
Yokoi, T, Fukuo, K, Yasuda, O, Hotta, M, Miyazaki, J, Takemura, Kawamoto, H, Ichijo, H, Ogihara, T
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Journal Title
Diabetes 55(6)
Pages: 1660-1665
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Study of Timp-3 expression and Renal Structure after Unilateral Ureteral Obstruction2007
Author(s)
Yasuda, O, Kawamoto, H, Higuchi, M, Baba, Y, Okita, M, Rakugi, H, Ogihara, T
Organizer
14st The Japanese Society for Gene Diagnosis and Therapy
Place of Presentation
Matsuyama
Year and Date
2007-07-27
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Two cases of Werner's Syndrome diagnosed by DNA analysis2006
Author(s)
Yasuda, O, Kawamoto, H, Shindo, N, Sugimoto, K, Fujisawa, T, Ohishi, M, Rakugi, H, Ogihara, T
Organizer
17st Japan Geriatric Society Meeting in Kinki
Place of Presentation
Osaka
Year and Date
2006-11-25
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Apop-1, a novel gene, inducing cyclophilin D-dependent apoptosis2006
Author(s)
Yasuda, O, Fukuo, K, Higuchi, M, Yotsui, T. Rakugi, H, Othhara, T
Organizer
21st International Society of Hypertension
Place of Presentation
Fukuoka
Year and Date
2006-10-16
Description
「研究成果報告書概要(欧文)」より
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