Calpain-2 Facilitates Autophagic/Lysosomal Defects and Apoptosis in ARPE-19 Cells and Rats Induced by Exosomes from RPE Cells under NaIO3 Stimulation.
Oxid Med Cell Longev
; 2023: 3310621, 2023.
Article
em En
| MEDLINE
| ID: mdl-36703913
ABSTRACT
Although accumulated evidence supports the notion that calpain contributes to eye disease, the mechanisms by which calpain promotes RPE injury are not defined. The present study is aimed at investigating whether the effect of NaIO3-exos (exosomes derived from RPE cells under NaIO3 stimulation) on the dysfunction of the autophagy-lysosomal pathway (ALP) and apoptosis is based on its regulation of calpain activation in ARPE-19 cells and rats. The results showed that calpain-2 activation, ALP dysfunction, and apoptosis were induced by NaIO3-exos in ARPE-19 cells. NaIO3-exo significantly increased autophagic substrates by activating lysosomal dysfunction. ALP dysfunction and apoptosis in vitro could be eliminated by knocking down calpain-2 (si-C2) or the inhibitor calpain-2-IN-1. Further studies indicated that NaIO3-exo enhanced calpain-2 expression, ALP dysfunction, apoptosis, and retinal damage in rats. In summary, these results demonstrate for the first time that calpain-2 is one of the key players in the NaIO3-exo-mediated ALP dysfunction, apoptosis, and retinal damage and identify calpain-2 as a promising target for therapies aimed at age-related macular degeneration (AMD).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Calpaína
/
Apoptose
/
Exossomos
Limite:
Animals
Idioma:
En
Revista:
Oxid Med Cell Longev
Assunto da revista:
METABOLISMO
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China