Development of a method to inhibit muscle atrophy by targeting accelerated Ca2+ reuptake into the sarcoplasmic reticulum

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K09511
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Tanihata Jun 東京慈恵会医科大学, 医学部, 講師 (00508426)
• Co-Investigator(Kenkyū-buntansha): 南沢 享 東京慈恵会医科大学, 医学部, 教授 (40257332) ; 暮地本 宙己 東京慈恵会医科大学, 医学部, 講師 (60632841)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: サルコリピン / 筋萎縮抑制 / SERCA機能 / 細胞内Ca2+濃度

Outline of Final Research Achievements

It is known that the expression of sarcoplasmic reticulum protein sarcolipin (SLN), which suppresses the function of sarcoplasmic reticulum Ca2+ ATPase (SERCA) to reuptake Ca2+ into the sarcoplasmic reticulum, is increased in atrophic skeletal muscle and muscle diseases, and the intracytoplasmic Ca2+ concentration is increased. Therefore, we hypothesized that "optimization of intracellular Ca2+ concentration by maintenance of sarcoplasmic reticulum Ca2+ reuptake function contributes to muscle homeostasis," and examined the effect of induction of muscle atrophy on the degree of muscle atrophy in response to SLN deletion. Unfortunately, induction of muscle atrophy in SLN KO mice resulted in muscle atrophy similar to the wild-type model of muscle atrophy, and no inhibitory effect on muscle atrophy was observed.

Free Research Field

筋生理

Academic Significance and Societal Importance of the Research Achievements

近年、SLNはcalcineurinを介して筋肥大に関わるという報告やSLN欠失では筋の再生が遅延するということが報告された。即ち、SLN欠失はSERCA機能を改善させる一方で、SLNは筋の恒常性維持にも関わるため、SLNの発現を抑制すると骨格筋の恒常性が損なわれる可能性が示唆された。そのため、細胞内Ca2+濃度の正常化を介した筋萎縮抑制法の開発に際し、SLNを標的することは適切ではない可能性がある。