| Project/Area Number |
03670584
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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 |
General surgery
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| Research Institution | Osaka University |
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Principal Investigator |
TSUJINAKA Toshimasa Osaka University Medical School, Department of Surgery II,assistant professor, 医学部, 助手 (40188545)
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| Co-Investigator(Kenkyū-buntansha) |
KIDO Yoshihiro Osaka University Medical Technology and Nursing School, Department of Nursing, a, 医学部, 助教授 (20116023)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1991: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Muscle protein degradation / Platelet / Disseminated intravascular coagulation / Protease / Inflammatory cytokine / Interleukin-6 / Myotube |
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| Research Abstract |
1.Muscle culture system : Muscle culture system was estabulished to examine protein degradation in soleus muscles obtained from young rats. Proteolysis inducing activity was found in the thrombin activated supernatant of human washed platelets.
2.Rat DIC model : DIC was introduced by the repeated injection of thrombin into rats. Apparent proteolysis was increased in the soleus muscles obtained from DIC rats. When the assay system for 3-methyl histidine was estabulished and the treatment of cycloheximide was performed, it was proven that protein synthesis but not degradation was suppressed in the muscles of DIC rats.
3.Myotubes : While L6 myoblasts were differenciated to myotubes, they showed the similar characteristics with the mature muscle. Intracellular proteases playd important roles in this differenciation step to myotubes in association with up-regulation of cathepsins and downregulation of proteasomes. C2C12 myotubes could be employed as a model of the mature muscle.
4.Proteolytic effect of inflammatory cytokines on C2C12 myotubes : Using C2C12 myotubes, proteolytic effects of inflammatory cytokines, such as TNF,IL-1 and IL-6, were examined. Solely IL-6 possesed proteolytic effect in association with an increase of enzymatic activitie of cathepsins (B,L) and 26S proteasome, and an enhanced transcription of cathepsins (B,L) and proteasomes mRNAs. It was concluded that IL-6 induces muscle protein degradation via activatio of intracellular proteolytic systems.
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