Polymyxin B Reduces Brain Injury in Ischemic Stroke Rat Through a Mechanism Involving Targeting ESCRT-III Machinery and RIPK1/RIPK3/MLKL Pathway.
J Cardiovasc Transl Res
; 15(5): 1129-1142, 2022 10.
Article
em En
| MEDLINE
| ID: mdl-35239171
ABSTRACT
Endosomal sorting complex required for transport III (ESCRT-III) machinery is a key component to counteract the mixed lineage kinase domain-like pseudokinase (MLKL)-induced plasma membrane broken in cells undergoing necroptosis. Based on the bioinformatics analysis, polymyxin B, a polypeptide antibiotic, is predicted to simultaneously interact with ESCRT-III subunits and necroptosis-relevant proteins. This study aims to explore whether polymyxin B could reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and/or suppressing the RIPK1/RIPK3/MLKL pathway. The stroke rats showed evident brain injury, concomitant with the downregulation of ESCRT-III subunits and the upregulation of necroptosis-relevant proteins. Post-ischemic administration of polymyxin B could alleviate the brain injury, accompanied by restoration of the levels of ESCRT-III subunits and suppression of necroptosis-relevant proteins. And, polymyxin B exerted similar effects in hypoxia-treated HT22 cells. We conclude that polymyxin B can reduce necroptosis in the stroke rat brain via enhancing the ESCRT-III machinery and suppressing the RIPK1/RIPK3/MLKL pathway simultaneously.
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Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
/
Acidente Vascular Cerebral
/
AVC Isquêmico
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article