Dysregulated autophagy is linked to BAX oligomerization and subsequent cytochrome c release in 6-hydroxydopmaine-treated neuronal cells
| Autor: | Young J. Oh, Yuhyun Chung, Yoonkyung Kim, Nuri Yun |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Biophysics Disuccinimidyl suberate Cellular homeostasis Apoptosis X-Linked Inhibitor of Apoptosis Protein Biochemistry Cell Line Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Autophagy medicine Animals Oxidopamine Molecular Biology bcl-2-Associated X Protein Cerebral Cortex Neurons chemistry.chemical_classification Reactive oxygen species biology Cytochrome c Neurodegeneration Cytochromes c Cell Biology medicine.disease Mitochondria XIAP Cell biology 030104 developmental biology nervous system chemistry Caspases 030220 oncology & carcinogenesis biology.protein Protein Multimerization |
| Zdroj: | Biochemical and Biophysical Research Communications. 548:20-26 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2021.02.045 |
| Popis: | Autophagy and apoptosis are essential physiological pathways that are required to maintain cellular homeostasis. Therefore, it is suggested that dysregulation in both pathways is linked to several disease states. Moreover, the crosstalk between autophagy and apoptosis plays an important role in pathophysiological processes associated with several neurodegenerative disorders. We have previously reported that 6-hydroxydopamine (6-OHDA)-triggered reactive oxygen species (ROS) induces dysregulated autophagy, and that a dysregulated autophagic flux contributes to caspase-dependent neuronal apoptosis. Based on our previous findings, we specifically aimed to elucidate the molecular mechanisms underlying the potential role of dysregulated autophagy in apoptotic neurodegeneration. The disuccinimidyl suberate (DSS) cross-linking assay and immunological analyses indicated that exposure of several types of cells to 6-OHDA resulted in BAX activation and subsequent oligomerization. Pharmacological inhibition and genetic perturbation of autophagy prevented 6-OHDA-induced BAX oligomerization and subsequent release of mitochondrial cytochrome c into the cytosol and caspase activation. These events were independent of expression levels of XIAP. Taken together, our results suggest that BAX oligomerization comprises a critical step by which 6-OHDA-induced dysregulated autophagy mediates neuronal apoptosis. |
| Databáze: | OpenAIRE |
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