The effects and regulatory mechanism of RIP3 on RGC-5 necroptosis following elevated hydrostatic pressure
| Autor: | Kun Xiong, Lei Shang, Na Li, Wei Ding, Jufang Huang, Lvshuang Liao, Dan Chen |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Retinal Ganglion Cells
0301 basic medicine Necrosis Necroptosis Blotting Western Hydrostatic pressure Biophysics Butylated Hydroxyanisole Apoptosis Biochemistry Antioxidants Cell Line Flow cytometry Mice 03 medical and health sciences 0302 clinical medicine Malondialdehyde Hydrostatic Pressure medicine Animals Kinase activity chemistry.chemical_classification Caspase 8 Reactive oxygen species medicine.diagnostic_test Chemistry Glycogen Phosphorylase General Medicine Flow Cytometry Up-Regulation Cell biology 030104 developmental biology Cell culture Receptor-Interacting Protein Serine-Threonine Kinases RNA Interference medicine.symptom Reactive Oxygen Species 030217 neurology & neurosurgery |
| Zdroj: | Acta Biochimica et Biophysica Sinica. 49:128-137 |
| ISSN: | 1672-9145 |
| DOI: | 10.1093/abbs/gmw130 |
| Popis: | Necroptosis is a type of regulated cell death that has been implicated in various diseases. Receptor-interacting protein 3 (RIP3), a member of the RIP family, is an important mediator of the necroptotic pathway. Cleavage of RIP3 at Asp328 by caspase-8 abolishes the kinase activity of RIP3, which is critical for necroptosis. Moreover, RIP3 is significantly upregulated during the early stages of acute high intra-ocular pressure and oxygen glucose deprivation. In this study, the effects of RIP3 during elevated hydrostatic pressure (EHP) were investigated and the possible mechanism through which caspase-8 regulated RIP3 cleavage was explored. Flow cytometry analysis revealed that the number of EHP-induced necrotic retinal ganglion cell 5 (RGC-5) cells was reduced after RIP3-knockdown. Furthermore, malondialdehyde (MDA) levels and glycogen phosphorylase (PYGL) activity in normal RGC-5 cells were much higher than those in RIP3-knockdown cells after EHP. EHP-induced RGC-5 necrosis was significantly reduced after treatment with butylated hydroxyanisole (BHA), a reactive oxygen species (ROS) scavenger. MDA levels and PYGL activity were lower in normal RGC-5 cells than those in cells with caspase-8 inhibition after EHP. Western blot analysis demonstrated that the RIP3 cleavage product was upregulated in cells with caspase-8 inhibition. Additionally, flow cytometry analysis revealed that the number of EHP-induced necrotic RGC-5 cells was increased after caspase-8 inhibition. Our results suggested that RGC-5 necroptosis following EHP was mediated by RIP3 through induction of PYGL activity and subsequent ROS accumulation. Thus, caspase-8 may participate in the regulation of RGC-5 necroptosis via RIP3 cleavage. |
| Databáze: | OpenAIRE |
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