2007 Fiscal Year Final Research Report Summary
Regulatory mechanism between autophagy and apoptosis in leukemia cells
| Project/Area Number |
18591089
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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 |
Hematology
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| Research Institution | Tokyo Medical University |
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Principal Investigator |
MIYAZAWA Keisuke Tokyo Medical University, School of Medicine, Associate Professor (50209897)
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| Co-Investigator(Kenkyū-buntansha) |
IGUCHI Tomotaka Tokyo Medical University, School of Medicine, Instructor (60408078)
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| Project Period (FY) |
2006 – 2007
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| Keywords | autophagy / apoptosis / leukemia / bcl-2 / cell death / vitamin K2 |
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| Research Abstract |
We investigated molecular based regulatory mechanism between autophagy and apoptosis.
Vitamin K2 (menaquinone-2 : VK2) is now known to be a potent inducer for apoptosis in leukemia cells in vitro. HL-60bc1-2 cells, which are derived from a stable transfectant clone of human bc1-2 gene into HL-60 leukemia cell line, show 5-fold greater expression of Bc1-2 protein compared with that in HL-60neo cells, a control clone transfected with vector alone. Although HL-60neo cells are induced apoptosis in response to VK2, HL-60bc1.2 cells are resistant against apoptosis induction but still show cell growth inhibition along with an increase of cytoplasmic vacuoles during exposure to VK2. Electron microscopy revealed autophagosomes and autolysosomes formation in HL-60bc1-2 cells after exposure to VK2. An increase of acid vesicular organelles (AVO) detected by acridine orange staining for lysosomes as well as conversion of LC3B-I into LC3B-II by immunonoblotting and an increased punctuated pattern of cytoplasmic LC3B by fluorescent immunostaining all supported enhanced autophagy induction in response to VK2 in HL-60bc1-2 cells. However, during shorter exposure to VK2, autophagosome formation was rather prominent in HL-60neo cells although nuclear chromatin condensations and nuclear fragments were also observed at the same time. These findings indicated the mixed morphologic features of apoptosis and autophagy. Inhibition of autophagy by either addition of 3-methyladenine, siRNA for Atg7, or Tet-off AtgS system all resulted in attenuation of VK2-incuded cell death, indicating autophagy-mediated cell death in response to VK2. These data demonstrate that autophagy and apoptosis can be simultaneously induced by VK2. However, autophagy becomes prominent when the cells were protected from rapid apoptotic death by higher expression level of Bcl-2.
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[Presentation] Vitamin K2 induces autophagy and apoptosis simultaneously in leukemia cells and Bc1-2 expression level determines the phenotype of their cell death2007
Author(s)
Keisuke, Miyazawa, Tomohisa, Yokoyama, Munekazu, Naito, Jun, Toyotake, Testuzo, Tauchi, Masahiro, Itoh, Akira, Yuo, Yasuko, Kondo, Seiji, Kondo, Kazuma, Ohyashiki
Organizer
The 48th Annual Meeting of American Society of Hematology
Year and Date
20071209-11
Description
「研究成果報告書概要(欧文)」より
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[Presentation] Simultaneous induction of autophagy and apoptosis in leukemic cells by vitamin K22007
Author(s)
Keisuke, Miyazawa, Tomohisa, Yokoyama, Juri, Toyotake, Akihiko, Gotoh, Munekazu, Naito, Masahiro, Ito, Akira, Yuo, Seiji, Kondo, Kazuma, Oyhashiki
Organizer
Keystone Symposium : Apopotis and non-apoptotic pathway
Year and Date
20070416-19
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 慢性骨髄増殖性疾患におけるJAK2-V617F変異の臨床血液所見の特徴2006
Author(s)
木口 亨, 大屋敷 一馬, 後藤 明彦, 赤羽 大悟, 田内 哲三, 伊藤 良和, 荘司 奈穂子, 岡部 聖一, 井口 具隆, 高久 智生, 山田 聖子, 布田 晃介, 豊武 寿理, 藤本 博昭, 宮澤 啓介, 木村 之彦, 大屋敷 純子
Organizer
第68回日本血液学会総会/第48回日本臨床血液学会総会(合同総会)
Place of Presentation
福岡
Year and Date
20060900
Description
「研究成果報告書概要(和文)」より
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