| Project/Area Number |
23K19925
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0909:Sports sciences, physical education, health sciences, and related fields
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| Research Institution | The University of Tokushima |
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Principal Investigator |
ULLA ANAYT 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (20980171)
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| Project Period (FY) |
2023-08-31 – 2025-03-31
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| Project Status |
Granted (Fiscal Year 2023)
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| Budget Amount *help |
¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2024: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2023: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 3D-Clinorotation, / MAM, / Mitochondria, / Mulberry Polyphenols, / Microgravity, / Tail suspension, / ER Stress / mulberry polyphenol / MAM |
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| Outline of Research at the Start |
Inactivity disrupts mitochondrial-associated ER membrane (MAM) integrity. So here I will investigate the effects of mulberry polyphenols in preventing MAM disruption thereby reducing metabolic abnormalities in inactivity-induced muscle using cell and animal model.
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| Outline of Annual Research Achievements |
Inactivity causes degradation of mitofusion-2 (MFN2) protein which disrupts mitochondrial-associated ER membrane (MAM) integrity. The MFN2 degradation further causes mitochondrial dysfunction and ER stress leading to metabolic abnormalities.
This year, I found by proximity ligation assay (PLA) analysis that 3D-clinorotation (microgravity-inducer) of C2C12 cells causes disruption of MAM structure. Furthermore, it decreases the MAM number, ATP production and MAM related protein, and increased the expression of Atrogin-1 and MuRF-1, markers for muscle atrophy. Morin and 4-oxyresveratrol were used against MAM disruption and related changes in C2C12 cells. This research is continued in siRNA treated MFN2 knokdown C2C12 cells. In the follow up study, animal experiment will be conducted.
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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
The research that has been planned earlier is progressing smoothly with the time span. The step by step experiments and analysis are being conducted and analysed. I belive that within the stipulated time, research outcomes can be obtained from both the cell and animal studies.
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| Strategy for Future Research Activity |
Currently,I am investigating and analysing the 3D-clinorotated (Control and MFN2 knockdown) C2C12 cells treated with polyphenols (Morin and 4-oxyresveratrol) to check the MAM integrity, mitochondrial function, oxidative stress and metabolic changes. In the follow up study, the animal (In vivo) experiments will be conducted to illustrate the changes in MAM integrity and energy regulations with the treatments of polyphenols in tail suspension-induced control and MFN2 knockout mice. I will also analyze the gastrocnemius muscle glucose metabolism in MFN2 muscle-specific knockout mice treated with polyphenols.
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