c-FLIP regulates pyroptosis in retinal neurons following oxygen-glucose deprivation/recovery via a GSDMD-mediated pathway
| Autor: | Dan Chen, Xiaobo Xia, Mi Wang, Hao Wan, Bing Jiang, Dan Ji, Bo Qin, Kun Xiong, Weitao Yan, Lvshuang Liao, Yanxia Huang, Qi Zhang, Fengxia Liu, Shuchao Wang, Fei Huang, Jufang Huang |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
CASP8 and FADD-Like Apoptosis Regulating Protein Inflammation Pathogenesis 03 medical and health sciences chemistry.chemical_compound In vivo medicine Pyroptosis Gene knockdown Retinal General Medicine Phosphate-Binding Proteins Cell biology Oxygen 030104 developmental biology Glucose chemistry Flip 030101 anatomy & morphology Anatomy medicine.symptom Adenosine triphosphate Developmental Biology Retinal Neurons |
| Zdroj: | Annals of anatomy = Anatomischer Anzeiger : official organ of the Anatomische Gesellschaft. 235 |
| ISSN: | 1618-0402 |
| Popis: | Cellular FLICE-inhibitory protein (c-FLIP), an anti-apoptotic regulator, shows remarkable similarities to caspase-8, which plays a key role in the cleavage of gasdermin D (GSDMD). It has been reported that the oxygen-glucose deprivation/recovery (OGD/R) model and lipopolysaccharide (LPS)/adenosine triphosphate (ATP) treatment could induce inflammation and pyroptosis. However, the regulatory role of c-FLIP in the pyroptotic death of retinal neurons is unclear. In this study, we hypothesized that c-FLIP might regulate retinal neuronal pyroptosis by GSDMD cleavage. To investigate this hypothesis, we induced retinal neuronal damage in vitro (OGD/R and LPS/ATP) and in vivo (acute high intraocular pressure [aHIOP]). Our results demonstrated that the three injuries triggered the up-regulation of pyroptosis-related proteins, and c-FLIP could cleave GSDMD to generate a functional N-terminal (NT) domain of GSDMD, causing retinal neuronal pyroptosis. In addition, c-FLIP knockdown in vivo ameliorated the already established visual impairment mediated by acute IOP elevation. Taken together, these findings revealed that decreased c-FLIP expression protected against pyroptotic death of retinal neurons possibly by inhibiting GSDMD-NT generation. Therefore, c-FLIP might provide new insights into the pathogenesis of pyroptosis-related diseases and help to elucidate new therapeutic targets and potential treatment strategies. |
| Databáze: | OpenAIRE |
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