2021 Fiscal Year Final Research Report
Involvement of Parkin-mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease-related sarcopenia
| Project/Area Number |
19K08612
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Jikei University School of Medicine |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
谷端 淳 東京慈恵会医科大学, 医学部, 助教 (00508426)
橋本 典生 東京慈恵会医科大学, 医学部, 助教 (00771742)
荒屋 潤 東京慈恵会医科大学, 医学部, 教授 (90468679)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 閉塞性肺疾患 / サルコペニア |
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| Outline of Final Research Achievements |
Parkin-mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF-1)-mediated myosin heavy chain (MHC) degradation. Parkin－/－ mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights and 2.3 times greater MuRF-1 expression compared to wild-type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression.
Taken together, COPD-related sarcopenia can be attributed to insufficient Parkin-mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF-1 activation.
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| Free Research Field |
肺癌、閉塞性肺疾患
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| Academic Significance and Societal Importance of the Research Achievements |
COPDの死亡リスク因子は身体活動性の低下であり、サルコペニアが関与しているが、サルコペニアの発症予防や治療薬はまだない状態である。COPD患者の骨格筋では活性酸素種(ROS)が増加し、ミトコンドリア障害が示唆されており、本研究では、COPD合併サルコペニアでは、不十分なParkin介在性マイトファジーによるROS産生と、それに伴うMuRF-1活性化が筋萎縮を引き起こす可能性が示唆された。本研究の成果が今後のCOPD合併サルコペニアの予防薬の開発に繋がる可能性があると考えられる。
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