RSK3 mediates necroptosis by regulating phosphorylation of RIP3 in rat retinal ganglion cells
| Autor: | Shuchao Wang, Kun Xiong, Bin Jiang, Yanxia Huang, Lvshuang Liao, Xiaobo Xia, Li-min Guo, Lei Shang, Fengxia Liu, Dan Ji, Jufang Huang, Mi Wang, Dan Chen, Hao Wan |
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| Rok vydání: | 2020 |
| Předmět: |
Retinal Ganglion Cells
0301 basic medicine Small interfering RNA Histology Necroptosis Regulator Ribosomal Protein S6 Kinases 90-kDa Retinal ganglion Cell Line Rats Sprague-Dawley Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Computer Simulation Phosphorylation Molecular Biology Ecology Evolution Behavior and Systematics Chemistry Kinase Original Articles Cell Biology Cell Hypoxia Rats Cell biology 030104 developmental biology medicine.anatomical_structure Retinal ganglion cell Receptor-Interacting Protein Serine-Threonine Kinases Ribosomal protein s6 Anatomy 030217 neurology & neurosurgery Signal Transduction Developmental Biology |
| Zdroj: | J Anat |
| ISSN: | 1469-7580 0021-8782 |
| DOI: | 10.1111/joa.13185 |
| Popis: | Receptor‐interacting protein 3 (RIP3) plays an important role in the necroptosis signaling pathway. Our previous studies have shown that the RIP3/mixed lineage kinase domain‐like protein (MLKL)‐mediated necroptosis occurs in retinal ganglion cell line 5 (RGC‐5) following oxygen‐glucose deprivation (OGD). However, upstream regulatory pathways of RIP3 are yet to be uncovered. The purpose of the present study was to investigate the role of p90 ribosomal protein S6 kinase 3 (RSK3) in the phosphorylation of RIP3 in RGC‐5 cell necroptosis following OGD. Our results showed that expression of RSK3, RIP3, and MLKL was upregulated in necroptosis of RGC‐5 after OGD. A computer simulation based on our preliminary results indicated that RSK3 might interact with RIP3, which was subsequently confirmed by co‐immunoprecipitation. Further, we found that the application of a specific RSK inhibitor, LJH685, or rsk3 small interfering RNA (siRNA), downregulated the phosphorylation of RIP3. However, the overexpression of rip3 did not affect the expression of RSK3, thereby indicating that RSK3 could be a possible upstream regulator of RIP3 phosphorylation in OGD‐induced necroptosis of RGC‐5 cells. Moreover, our in vivo results showed that pretreatment with LJH685 before acute high intraocular pressure episodes could reduce the necroptosis of retinal neurons and improve recovery of impaired visual function. Taken together, our findings suggested that RSK3 might work as an upstream regulator of RIP3 phosphorylation during RGC‐5 necroptosis. |
| Databáze: | OpenAIRE |
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