Role of the SIRT1/p53 regulatory axis in oxidative stressmediated granulosa cell apoptosis.
Mol Med Rep
; 23(1)2021 01.
Article
em En
| MEDLINE
| ID: mdl-33179088
ABSTRACT
Oxidative stress has been suggested to induce granulosa cell apoptosis, which contributes to follicular atresia. However, the mechanism via which oxidative stress mediates granulosa cell apoptosis remains elusive. Therefore, the aim of this study was to elucidate the molecular mechanisms regulating oxidative stressinduced granulosa cell apoptosis. The present study demonstrated that reactive oxygen species induced by H2O2 resulted in human granulosa COV434 cell apoptosis via the regulation of sirtuin 1 (SIRT1)mediated p53 activity. Endogenous SIRT1 expression was alleviated by H2O2 treatment of COV434 cells in a timedependent manner. In addition, knockdown or inhibition of SIRT1 promoted H2O2induced poly(ADPribose) polymerase (PARP) cleavage and p53 acetylation, which led to an increase in COV434 cell apoptosis. Treatment with H2O2 enhanced the expression levels of the p53dependent proteins, p53upregulated modulator of apoptosis (PUMA) and phorbol12myristate13acetateinduced protein 1 (PMAIP1), as well as those of p53; however, knockdown of p53 decreased cleaved PARP, PUMA and PMAIP1 expression levels induced by H2O2 treatment. Moreover, knockdown of PUMA or PMAIP1 attenuated the H2O2 induction of PARP cleavage and COV434 cell apoptosis. In conclusion, the present findings suggested that H2O2induced oxidative stress causes granulosa COV434 cell apoptosis via the upregulation of p53 activity by SIRT1 suppression, indicating a mechanistic role of the SIRT1/p53 axis in H2O2induced granulosa cell apoptosis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteína Supressora de Tumor p53
/
Sirtuína 1
/
Células da Granulosa
/
Peróxido de Hidrogênio
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article