Tomatidine provides mitophagy‐independent neuroprotection after ischemic injury
| Autor: | Anil Ahsan, Li-na Zhang, Zikai Feng, Xiangnan Zhang, Yu-ting Wang, Yue Li, Xiao-cui Lyu |
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| Rok vydání: | 2021 |
| Předmět: |
autophagy
Cell Survival QH301-705.5 Ischemia Mitochondrion Pharmacology Neuroprotection cerebral ischemia General Biochemistry Genetics and Molecular Biology Brain Ischemia Neuroblastoma cell Mice Tomatine Cell Line Tumor Mitophagy medicine Animals Humans Translocase Biology (General) Research Articles Neurons biology business.industry Autophagy Ischemic injury medicine.disease Mitochondria Oxygen Glucose Neuroprotective Agents mitophagy biology.protein business tomatidine Research Article |
| Zdroj: | FEBS Open Bio, Vol 11, Iss 9, Pp 2647-2654 (2021) FEBS Open Bio |
| ISSN: | 2211-5463 |
| DOI: | 10.1002/2211-5463.13265 |
| Popis: | Cerebral ischemia is one of the leading causes of human mortality and disability worldwide. The treatment of cerebral ischemia is refractory due to its short therapeutic window and lack of effective clinical drugs. Mitophagy, the autophagic elimination of damaged mitochondria, attenuates neuronal injury in cerebral ischemia, indicating the potential of mitophagy inducers as therapies for cerebral ischemia. We previously determined that, by enhancing autophagy flux, the steroidal alkaloid tomatidine can function as a neuroprotective agent against ischemic injury. However, its effects on mitophagy remain unknown. For this purpose, neuroblastoma cell lines Neuro‐2a and SH‐SY5Y were subjected to ischemic injury induced by oxygen–glucose deprivation/reperfusion (OGD/R) and then treated with tomatidine. OGD/R induced a general decrease of cellular contents, and this study revealed that tomatidine had no impact on mitophagy. In addition, tomatidine did not affect mitochondrial contents, including translocase of outer mitochondrial membrane 20 and voltage‐dependent anion channel 1, in either OGD/R‐treated or intact SH‐SY5H cells. Our results indicate that tomatidine exhibits its neuroprotective effects by enhancing autophagy, but in a potentially mitophagy‐independent manner, and provide insights for further investigation into its mechanism(s) and potential therapeutic use against cerebral ischemia. The steroidal alkaloid, tomatidine, has been shown to treat cerebral ischemia by enhancing autophagy, but its effect on mitophagy is still unknown. Our work indicates that the neuroprotective role of tomatidine is independent of mitophagy. Further research should be performed to determine how autophagy contributes to the neuroprotective effects of tomatidine in ischemic neurons. |
| Databáze: | OpenAIRE |
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