The effects of 3-methylhistidine on myosin degradation in skeletal muslce

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22609
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Niigata University
• Principal Investigator: Shimamoto Saki 新潟大学, 自然科学系, 助教 (90875395)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 骨格筋 / タンパク質分解 / Nτ-メチルヒスチジン

Outline of Final Research Achievements

Skeletal muscle mass is controlled through a delicate balance between protein synthesis and degradation. The mechanisms by which control protein synthesis and degradation are important for proper control of skeletal muscle mass. 3-methylhistidine (3-MeHis) is formed by post-translational methylation of the histidine residue involved in myosin and actin, which occupy a large part of myofibrillar proteins. Since this amino acid has been considered to be rapidly effused from skeletal muscle, its biological activity in skeletal muscles remains unclear. However, considerable amount of intercellular free 3-MeHis was actually detected in skeletal muscle.In this study, to investigate biological roles of 3-MeHis in skeletal muscle, we examined the effects of medium supplementation with 3-MeHis on myofibrillar protein levels in C2C12 myotubes.
Supplementation of 3-MeHis decreased myofibrillar protein via the dual pathway of autophagy-lysosome and Ub-proteasome in C2C12 myotubes.

Free Research Field

動物生産科学

Academic Significance and Societal Importance of the Research Achievements

本研究はタンパク質分解機構の全容解明の一助となり、また遺伝子に暗号化されていないアミノ酸の機能の重要性を発信する研究となる。また、3メチルヒスチジンが「生体にとって不要で速やかに体外に排出される」という考え方から、「筋原線維タンパク質の分解産物である3-MeHisが連鎖的な筋原線維タンパク質の分解を惹起する」という考え方へのパラダイムシフトを提示することができ、加えて、3-MeHisは、イミダゾールジペプチドであるバレニンを構成するアミノ酸であるため、タンパク質分解に対するイミダゾールジペプチドの作用に焦点を当てた研究への波及が期待されると考えられる。