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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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,890,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥390,000)
Fiscal Year 2007: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2006: ¥2,200,000 (Direct Cost: ¥2,200,000)
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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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Report
(3 results)
Research Products
(39 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)
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Geriatrics and Gerontology International 7
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Arteriosclerosis, thrombosis, and vascular biology 27(10)
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FEBS letters 581(3)
Pages: 427-432
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Higuchi, M, Yasuda, O, Kawamoto, H, Yotsui, T, Baba, Y, Ozaki, T, Maeda, N, Fukuo, K, Rakugi, H, Ogihara, T
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Hypertension Research 30(6)
Pages: 563-571
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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 of Biological Chemistry 281(33)
Pages: 23899-23907
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[Journal Article] Tissue inhibitor of metalloproteinase-3 plays important roles in the kidney following unilateral ureteral obstruction2006
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Hypertension Research 29(4)
Pages: 285-294
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Hypertension Research 29(4)
Pages: 217-225
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[Journal Article] Apoptosis Signal-Regulating Kinase 1 Mediates Cellular Senescence Induced by High Glucose in Endothelial Cells2006
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Yokoi, T, Fukuo, K, Yasuda, O, Hotta, M, Miyazaki, J, Takemura, Kawamoto, H, Ichijo, H, Ogihara, T
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Diabetes 55(6)
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[Presentation] Apop蛋白質の機能解析2007
Author(s)
安田 修
Organizer
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Place of Presentation
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Year and Date
2007-07-28
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[Presentation] Study of Timp-3 expression and Renal Structure after Unilateral Ureteral Obstruction2007
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Organizer
14st The Japanese Society for Gene Diagnosis and Therapy
Place of Presentation
Matsuyama
Year and Date
2007-07-27
Description
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[Presentation] Apop遺伝子の機能解析2007
Author(s)
安田 修
Organizer
第1回 地域健康科学研究会
Place of Presentation
西宮
Year and Date
2007-01-31
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[Presentation] Two cases of Werner's Syndrome diagnosed by DNA analysis2006
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Organizer
17st Japan Geriatric Society Meeting in Kinki
Place of Presentation
Osaka
Year and Date
2006-11-25
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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
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