Upregulation of ubiquitinated proteins and their degradation pathway in muscle atrophy induced by cisplatin in mice.
Toxicol Appl Pharmacol
; 403: 115165, 2020 09 15.
Article
en En
| MEDLINE
| ID: mdl-32738330
ABSTRACT
We previously demonstrated that cisplatin administration in mice induces muscle atrophy and an increase in the expression of two muscle-specific ubiquitin E3 ligase genes, muscle ring finger protein 1 (MuRF1), and atrophy gene-1 (atrogin-1), in skeletal muscle. Ubiquitination serves as a degradation signal in both the ubiquitin-proteasome and selective autophagy pathways. In the present study, we investigated changes in the expression of ubiquitin and ubiquitinated proteins and their degradation pathways. Ubiquitin and ubiquitinated protein levels were increased by cisplatin compared with those in the vehicle and dietary restriction (DR) groups. To quantify the levels of ubiquitin and ubiquitinated proteins, we conducted a dot blot assay using an anti-ubiquitin antibody. The expression of ubiquitin was also significantly increased by cisplatin compared with that in the vehicle and DR groups. Since the ubiquitin proteins were upregulated by cisplatin, we measured the mRNA levels of the ubiquitin genes Ubb, Ubc, Rps27a, and Uba52. All these four genes were increased by cisplatin administration compared with those in both the vehicle-treated and DR groups in quadriceps muscle tissue. The anti-ubiquitin antibody-sensitive bands increased when C2C12 myotubes were treated with cisplatin. Furthermore, MG-132 (26 s proteasome inhibitor), but not bafilomycin A1 (autophagy inhibitor), caused a further increase in expression. In conclusion, ubiquitin and ubiquitinated proteins are upregulated in cisplatin-induced muscle atrophy. Cisplatin-induced ubiquitinated proteins are degraded by the 26 s proteasome pathway.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Atrofia Muscular
/
Regulación hacia Arriba
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Regulación de la Expresión Génica
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Cisplatino
/
Proteínas Ubiquitinadas
Límite:
Animals
Idioma:
En
Revista:
Toxicol Appl Pharmacol
Año:
2020
Tipo del documento:
Article