Protosappanin A Maintains Neuronal Mitochondrial Homeostasis through Promoting Autophagic Degradation of Bax
| Autor: | Ke-Wu Zeng, Xin Dong, Yan-Jun Wan, Yang Liu, Li-Xi Liao, Peng-Fei Tu, Jing-Kang Wang |
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| Rok vydání: | 2020 |
| Předmět: |
Mitochondrial DNA
Physiology Cognitive Neuroscience Ischemia Reversion Apoptosis Biochemistry Phenols Puma medicine Autophagy Animals Homeostasis Mitochondrial homeostasis bcl-2-Associated X Protein biology Chemistry Effector Cell Biology General Medicine biology.organism_classification medicine.disease Cell biology Mitochondria Rats Function (biology) |
| Zdroj: | ACS chemical neuroscience. 11(24) |
| ISSN: | 1948-7193 |
| Popis: | Cerebral ischemia is accompanied by mitochondrial integrity destruction. Thus, reversion of mitochondrial damage holds great potential for cerebral ischemia therapy. As a crucial Bcl-2 family member, pro-apoptotic Bax protein is a main effector of mitochondrial permeabilization and plays an important role in mitochondrial homeostasis. However, there is still a lack of an effective cerebral protective strategy through selectively targeting Bax. In this study, we reported that natural small-molecule protosappanin A (PTA) showed a significant mitochondrial protective effect on oxygen-glucose deprivation/reperfusion (OGD/R)-induced PC12 cells injury through increasing ATP production and maintaining mitochondrial DNA (mtDNA) content. The mechanism study revealed that PTA selectively induced pro-apoptotic protein Bax degradation, without affecting other Bcl-2 family members such as Bcl-2, Bcl-xl, Bad, Puma, Bid, Bim, and Bik. In addition, we found that PTA promoted the association of autophagosomal marker LC3B to Bax for its degradation via an autophagy-dependent manner but not the ubiquitin-proteasome pathway. Collectively, our findings offered a new pharmacological strategy for maintaining mitochondrial function by inducing autophagic degradation of Bax and also provided a novel drug candidate against ischemic neuronal injury. |
| Databáze: | OpenAIRE |
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