Pro-caspase-3 protects cells from polymyxin B-induced cytotoxicity by preventing ROS accumulation.
J Antibiot (Tokyo)
; 72(11): 848-852, 2019 11.
Article
em En
| MEDLINE
| ID: mdl-31371783
ABSTRACT
Polymyxin B (PMB), a last-line antibiotic used against antibiotic-resistant superbugs, causes undesirable cytotoxic side effects. However, its mechanisms remain unknown. In this study, we unexpectedly found that caspase-3, a main executor of apoptosis, plays a protective role in PMB-induced cytotoxicity. Caspase-3 knockout (KO) cells exhibited higher susceptibility to PMB-induced cytotoxicity compared with wild-type (WT) cells, accompanied by increased levels of reactive oxygen species (ROS). Interestingly, co-treatment with the antioxidant N-acetylcysteine (NAC) rescued cell viability to a similar extent as WT cells. Furthermore, PMB failed to facilitate the processing of inactive caspase-3 (pro-caspase-3) into active forms, suggesting that pro-caspase-3 nonenzymatically suppresses PMB-driven ROS accumulation and its cytotoxicity. Thus, our findings that demonstrate the potential ability of PMB to stimulate ROS generation, but which is normally masked by pro-caspase-3-dependent mechanisms, may provide novel insights into the mechanisms of PMB-induced side effects.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Polimixina B
/
Espécies Reativas de Oxigênio
/
Caspase 3
/
Antibacterianos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
J Antibiot (Tokyo)
Ano de publicação:
2019
Tipo de documento:
Article