2005 Fiscal Year Final Research Report Summary
IDENTIFICATION OF THE CAUSATIVE GENES RESPONSIBLE FOR ERYTHROID APOPTOSIS INDUCED BY GLYCOLYTIC INHIBITION
| Project/Area Number |
16590254
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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 |
Pathological medical chemistry
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| Research Institution | TOKYO WOMEN'S MEDICAL UNIVERSITY |
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Principal Investigator |
KANNO HITOSHI TOKYO WOMEN'S MEDICAL UNIVERSITY, FACULTY OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (70221207)
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| Co-Investigator(Kenkyū-buntansha) |
AISAKI KEN-ICHI NATIONAL INSTITUTE OF HEALTH AND SCIENCES, DIVISION OF TOXICOLOGY, 毒性部, 研究員 (40322086)
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| Project Period (FY) |
2004 – 2005
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| Keywords | hemolytic anemia / inborn error of metabolism / red cell life span / anti-oxidant |
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| Research Abstract |
We previously established a Friend erythroleukemic cell, SLC3, from the mice model of red blood cell pyruvate kinase (R-PK) deficiency. SLC3 showed spontaneous apoptosis during routine passage. When cultured in a condition of glucose deprivation or supplementation with 2-deoxyglucose, a control Friend cell, CBA2, also showed apoptosis. Preincubation with N-acetyl cysteine, glutathione precursor, reduces apoptosis of CBA2 induced by 2-deoxyglucose, suggesting that glycolytic inhibition increases oxidative stress in erythroid cells and that erythroid apoptosis is likely to be induced by reactive oxygen species (ROS).
When cultured in 5mM phosphoenolpyruvate (PEP) for 48 hours, intracellular concentration of PEP and pyruvate increased up to 7- and 2-times, respectively. ROS in the PEP-treated erythroid cells significantly decreased, and apoptotic cell number decreased about 50% of non-treated cells. This observation suggests that accumulation of PEP improves glycolysis since the mutant R-PK has lower substrate specificity due to the active site mutation. Taken together, we conclude that glycolytic inhibition increases oxidative stress in erythroid cells and activate proapoptotic gene expressions, leading to apoptosis.
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Research Products
(12 results)
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[Journal Article] Ineffective erythropoiesis in mutant mice with deficient pyruvate kinase activity.2005
Author(s)
Aizawa, S., Harada, T., Kanbe, E., Tsuboi, I., Aisaki, K., Fujii, H., Kanno, H.
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Journal Title
Exp Hematol 33
Pages: 1292-1298
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Cyclic polylactate inhibited growth of cloned leukemic cells through reducing glycolytic enzyme activities.2005
Author(s)
Harada, T., Nagasu, M., Tsuboi, I., Koshinaga, M., Kanno.H., Aizawa, S.
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Journal Title
Oncol Rep 14
Pages: 501-505
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Histopathological study of lattice corneal dystrophy with L 527 R mutation of transforming growth factor-beta induced gene.2004
Author(s)
Nakagawa, E., Sakimoto, T., Inada, N., Shoji, J., Sawa, M., Kanno, H., Nakagawa, S.
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Journal Title
Nippon Ganka Gakkai Zasshi 108
Pages: 118-123
Description
「研究成果報告書概要(欧文)」より
