1994 Fiscal Year Final Research Report Summary
Mitochondrial gene expression in cell death and differentiation of leukemic cells
| Project/Area Number |
05670914
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Seinan Jogakuin University (1994)
Kyushu University (1993) |
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Principal Investigator |
KUDO Jiro Seinan Jogakuin University, Faculty of Health and Welfare, Associate Professor, 保険福祉学部, 助教授 (90148940)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHIDA Kazuhiro Kyushu University, Faculty of Medicine, Assistant, 医学部, 助手 (60180981)
ISHIBASHI Hiromi Kyushu University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (80127969)
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| Project Period (FY) |
1993 – 1994
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| Keywords | mitochondria / cellular differentiation / apoptosis / NADH dehydrogenase / leukemia / rotenone / mitochondrial inhibitor / HL60 cells |
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| Research Abstract |
In the previous study we elucidated that the mitochondrial NADH dehydrogenase gene was over expressedin leukemic cells, suggesting the gene expression could be related to the myeloid differentiation. So we investigated in this study the effect of rotenone, a specific NADH dehydrogenase inhibitor, on HL60cell growth, differentiation and cell death.
Fifty nM rote non inhibited the growth of HL60 cells and caused an increase in the cell population in the G2 + M phase. In the quantitative comparison of myeloid antigen, the expression of CD13 and CD38 were relatively increasedin the rote non-treated cells. These finding suggest that the inhibition of NADH dehydrogenase changes the cell cycle and induces the differentiation of HL60 cells. On the other hand, the expression of ND2 gene remained unchanged after the rote non treatment, suggesting the rote non-mediated mitochondrial inhibition did not affect the mitochondrial gene expression.
Five muM rote non strongly inhibited the cellular proliferation and electron microscopy and an electrophoretic analysis of DNA showed that the majority of the HL60 cells were induced into typical apoptosis within 24 to 48 hours. On the basis of this and other studies, we believe that mitochondrial junction is directory involved in both cellular differentiation and apoptotic cell death.
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