The role of iron on sarcopenia, and the therapeutic significance of iron regulation for anti-sarcopenia

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K01716
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: The University of Tokushima
• Principal Investigator: IKEDA Yasumasa 徳島大学, 大学院医歯薬学研究部(医学系), 准教授 (60432754)
• Co-Investigator(Kenkyū-buntansha): 八木 秀介 徳島大学, 大学院医歯薬学研究部, 特任准教授 (00507650)
• Co-Investigator(Renkei-kenkyūsha): HORINOUCHI Yuya 徳島大学, 大学院医歯薬学研究部(医学系), 助教 (30716593)
• Research Collaborator: HAMANO Hirofumi 徳島大学, 大学院医歯薬学研究部(医学系), 大学院生 ; IMAO Mizuki 徳島大学, 大学院医歯薬学研究部(薬学系), 学部生 ; SATO Akiho 徳島大学, 大学院医歯薬学研究部(薬学系), 学部生 ; WATANABE Hiroaki 徳島大学, 大学院医歯薬学研究部(薬学系), 学部生
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: 鉄 / サルコペニア / 酸化ストレス

Outline of Final Research Achievements

Skeletal muscle atrophy is a critical health problem. However, the effect of iron on skeletal muscle atrophy has remained unclear. Mice with excess iron-injected group showed the reduced skeletal muscle mass. The skeletal muscle with iron treatment showed elevated mRNA expression of the muscle atrophy-related E3 ubiquitin ligases, atrogin-1 and muscle ring finger-1(MuRF1). Moreover, iron-treated mice showed reduced phosphorylation of Akt and forkhead box O3 (FOXO3a) in skeletal muscles. In in vitro experiments using C2C12 myotube cells, FOXO3a siRNA inhibited iron-induced upregulation of atrogin-1 and MuRF1 and reversed the reduction in myotube diameters. Iron-load caused oxidative stress, and an oxidative stress inhibitor abrogated iron-induced muscle atrophy by recovering the reduced phosphorylation of Akt-FOXO3a pathway. Iron-induced skeletal muscle atrophy is suggested to involve the inactivation of Akt-FOXO3a-E3 ubiquitin ligase signaling by oxidative stress.

Free Research Field

薬理学、循環器内科学、内分泌代謝学、腎臓内科学