2004 Fiscal Year Final Research Report Summary
Apoptosis in DNase g deficient mic
| Project/Area Number |
14370752
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | TOKYO UNIVERSITY OF SCIENCE |
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Principal Investigator |
TANUMA Seiichi TOKYO UNIVERSITY OF SCIENCE, FACULTY OF PHARMACEUTICAL SCIENCES, 薬学部, 教授 (10142449)
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| Co-Investigator(Kenkyū-buntansha) |
MARUTA Hideharu TOKYO UNIVERSITY OF SCIENCE, FACULTY OF PHARMACEUTICAL SCIENCES, 薬学部, 助手 (00266917)
SHIOKAWA Daisuke TOKYO UNIVERSITY OF SCIENCE, FACULTY OF PHARMACEUTICAL SCIENCES, 薬学部, 助手 (90277278)
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| Project Period (FY) |
2002 – 2004
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| Keywords | apoptosis / DNase gamma / knockout mice / class switch / autoimmune / disease / self antigen |
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| Research Abstract |
The internucleosomal cleavage of chromosomal DNA is the biochemical feature most commonly associated with apoptotic cell death. Our laboratory has been reported the purification and cloning of endonuclease DNase γ, the nuclease responsible for DNA fragmentation during apoptosis.
DNase γ deficient mice was healthy, thus this result means DNase γ has not important role in ontogeny.
Next, RT-PCR analysis indicated that expression of DNase γ was highly induced when splenocytes were stimulated with α-CD40+IL-4. On the other hand, expression of CAD (Caspase Activated DNase), which has been suggested commonly to be responsible for apoptotic DNA fragmentation, was not induced. In addition, expression of ICAD (Inhibitor of CAD), which inhibit the activity of CAD, was reduced and disappeared during activation of B cells. Thus, these results suggest that the CAD-ICAD system does not work during activation of B cells, and activated CAD does not exist. Then splenic B cells were purified and activated with α-CD40+IL-4, and the cells were induced apoptosis by α-Fas antibody. The results indicated that the nucleosomal DNA fragmentation was inhibited in DNase γ deficient mice. It seems that DNase γ is responsible for DNA fragmentation in order to remove the self-reactive B cells and to finish immunological reaction rapidly.
In this report, we have shown the physiological analysis of DNase γ in vivo, and indicated that DNase γ is responsible for nucleosomal DNA fragmentation in the activation-induced apoptosis of B cells in immunological tissues.
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