Propofol inhibits parthanatos via ROS-ER-calcium-mitochondria signal pathway in vivo and vitro.
Cell Death Dis
; 9(10): 932, 2018 09 17.
Article
em En
| MEDLINE
| ID: mdl-30224699
ABSTRACT
Parthanatos is a new form of programmed cell death. It has been recognized to be critical in cerebral ischemia-reperfusion injury, and reactive oxygen species (ROS) can induce parthanatos. Recent studies found that propofol, a widely used intravenous anesthetic agent, has an inhibitory effect on ROS and has neuroprotective in many neurological diseases. However, the functional roles and mechanisms of propofol in parthanatos remain unclear. Here, we discovered that the ROS-ER-calcium-mitochondria signal pathway mediated parthanatos and the significance of propofol in parthanatos. Next, we found that ROS overproduction would cause endoplasmic reticulum (ER) calcium release, leading to mitochondria depolarization with the loss of mitochondrial membrane potential. Mitochondria depolarization caused mitochondria to release more ROS, which, in turn, contributed to parthanatos. Also, we found that propofol inhibited parthanatos through impeding ROS overproduction, calcium release from ER, and mitochondrial depolarization in parthanatos. Importantly, our results indicated that propofol protected cerebral ischemia-reperfusion via parthanatos suppression, amelioration of mitochondria, and ER swelling. Our findings provide new insights into the mechanisms of how ER and mitochondria contribute to parthanatos. Furthermore, our studies elucidated that propofol has a vital role in parthanatos prevention in vivo and in vitro, and propofol can be a promising therapeutic approach for nerve injury patients.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Contexto em Saúde:
6_ODS3_enfermedades_notrasmisibles
Problema de saúde:
6_cerebrovascular_disease
Assunto principal:
Propofol
/
Cálcio
/
Morte Celular
/
Espécies Reativas de Oxigênio
/
Retículo Endoplasmático
/
Mitocôndrias
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Death Dis
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
China