Pathological implication of CaMKII in NF-κB pathway and SASP during cardiomyocytes senescence.
Mech Ageing Dev
; 209: 111758, 2023 01.
Article
em En
| MEDLINE
| ID: mdl-36462537
ABSTRACT
Senescence-associated secretory phenotype (SASP) could be developed during heart ageing. But the role of SASP in cardiomyocytes senescence and its molecular mechanism remains undetermined. In this study, we observed elevated Ca2+/calmodulin -dependent protein kinase II (CaMKII) activation in both physiological aged heart and premature senescent cardiomyocytes. Notably, we confirmed the gradual SASP development induced by NF-κB activation in long-term cultured cardiomyocytes. Transgenic inhibition of CaMKII in mice (AC3-I mice) alleviated the NF-κB activation, chronic sterile inflammation and ageing-associated cardiomyopathy. Correspondingly, pharmacological inhibition of CaMKII with KN93 mitigated SASP and hindered cardiomyocytes senescence. Meanwhile, increased NF-κB activation and exacerbated cardiomyocytes senescence were observed with transgenic CaMKII activation. Collectively, our results indicated that the increased CaMKII activation accompanying ageing could aggravate NF-κB activation and SASP development and facilitate cardiomyocytes senescence and heart ageing.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
NF-kappa B
/
Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina
Limite:
Animals
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article