RRC ID 75768
著者 Sato K, Miyauchi Y, Xu X, Kon R, Ikarashi N, Chiba Y, Hosoe T, Sakai H.
タイトル Platinum-based anticancer drugs-induced downregulation of myosin heavy chain isoforms in skeletal muscle of mouse.
ジャーナル J Pharmacol Sci
Abstract Cisplatin, a platinum-based anticancer drug used frequently in cancer treatment, causes skeletal muscle atrophy. It was predicted that the proteolytic pathway is enhanced as the mechanism of this atrophy. Therefore, we investigated whether a platinum-based anticancer drug affects the expression of the major proteins of skeletal muscle, myosin heavy chain (MyHC). Mice were injected with cisplatin or oxaliplatin for four consecutive days. C2C12 myotubes were treated using cisplatin and oxaliplatin. Administration of platinum-based anticancer drug reduced quadriceps mass and muscle strength compared to the control group. Protein levels of all MyHC isoforms were reduced in the platinum-based anticancer drug groups. However, only Myh2 (MyHC-IIa) gene expression in skeletal muscle of mice treated with platinum-based anticancer drugs was found to be reduced. Treatment of C2C12 myotubes with platinum-based anticancer drugs reduced the protein levels of all MyHCs, and treatment with the proteasome inhibitor MG-132 restored this reduction. The expression of Mef2c, which was predicted to act upstream of Myh2, was reduced in the skeletal muscle of mice treated systemically with platinum-based anticancer drug. Degradation of skeletal muscle MyHCs by proteasomes may be a factor that plays an important role in muscle mass loss in platinum-based anticancer drug-induced muscle atrophy.
巻・号 152(3)
ページ 167-177
公開日 2023-7-1
DOI 10.1016/j.jphs.2023.04.009
PII S1347-8613(23)00030-0
PMID 37257944
MeSH Animals Antineoplastic Agents* / pharmacology Atrophy / metabolism Cisplatin Down-Regulation Mice Muscle Fibers, Skeletal / metabolism Muscle, Skeletal / metabolism Myosin Heavy Chains* / genetics Myosin Heavy Chains* / metabolism Oxaliplatin Platinum / metabolism Protein Isoforms / genetics Protein Isoforms / metabolism
IF 2.835
リソース情報
ヒト・動物細胞 C2C12(RCB0987)