Eicosapentaenoic acid suppresses cisplatin-induced muscle atrophy by attenuating the up-regulated gene expression of ubiquitin

• Published in: The Journal of nutritional biochemistry 2022-05, Vol.103, p.108953-108953, Article 108953
• Main Authors: Ikeno, Yohei, Inomata, Maya, Tsukimura, Yuka, Suzuki, Yuta, Takeuchi, Hiroto, Harada, Yui, Kon, Risako, Ikarashi, Nobutomo, Chiba, Yoshihiko, Yamada, Takeshi, Kamei, Junzo, Sakai, Hiroyasu
• Format: Article
• Language: English
• Subjects: Animals; Cisplatin; Cisplatin - adverse effects; Eicosapentaenoic acid; Eicosapentaenoic Acid - metabolism; Gene Expression; Humans; Mice; Muscle atrophy; Muscle Proteins - genetics; Muscle Proteins - metabolism; Muscle, Skeletal - metabolism; Muscular Atrophy - chemically induced; Muscular Atrophy - prevention & control; Proteasome; SKP Cullin F-Box Protein Ligases - genetics; SKP Cullin F-Box Protein Ligases - metabolism; SKP Cullin F-Box Protein Ligases - pharmacology; Ubiquitin; Ubiquitin - metabolism; Ubiquitin-Protein Ligases - metabolism; Ubiquitinated Proteins - genetics; Ubiquitinated Proteins - metabolism; Ubiquitinated Proteins - pharmacology
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2022.108953

Previously it was shown that cisplatin causes muscle atrophy. Under this condition, cisplatin increased the expression of atorogenes, such as muscle ring finger 1 and atrogin-1 (also known as muscle atrophy F-box protein), in mouse skeletal muscle. It was reported recently that ubiquitin (Ub) and ubiquitinated protein levels in skeletal muscle were also up-regulated in cisplatin-induced muscle atrophy, and cisplatin-induced ubiquitinated proteins were degraded by the 26S proteasome pathway. Eicosapentaenoic acid (EPA) is effective against skeletal muscle atrophy in mice. However, it is unclear how EPA suppresses the Ub–proteasome pathway. In this study, the effect of EPA on cisplatin-induced muscle atrophy in mice was examined. Mice were intraperitoneally injected with cisplatin or vehicle control once daily for 4 d. EPA or its vehicle was orally administered 30 min before cisplatin administration. Cisplatin systemic administration induced decrease in muscle mass, myofiber diameter, and increase in Ub genes and ubiquitinated proteins in mouse skeletal muscle were recovered by co-treatment with EPA. However, weight loss and up-regulated atrogenes induced by cisplatin were not changed by co-treatment with EPA in skeletal muscle. In this study, EPA attenuated cisplatin-induced muscle atrophy via down-regulation of up-regulated Ub gene expression. Although further clinical studies are needed, EPA administration can be effective in the development of muscle atrophy in cisplatin-treated patients.