| Autor: |
Jing Tian, Yi-Yue Zhang, Ya-Wei Peng, Bin Liu, Xiao-Jie Zhang, Zhong-Yang Hu, Chang-Ping Hu, Xiu-Ju Luo, Jun Peng |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
Journal of cardiovascular translational research. 15(5) |
| ISSN: |
1937-5395 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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