Abstract
Ischemia stroke has become the second leading cause of death in adult population. It could cause sereve cognitive and motor dysfunction, neurodegenerative disease, and even acute death. Ischemia stroke could lead cells expose to the environment without oxygen and glucose, and induce autophagy, apoptosis and necrosis pathways. It has been known that autophagy plays an important role in ischemia stroke; however, whether the autophagy mitigates or exacerbates the brain injury is still controversial. Phellinus linteus, an orange Basidiomycete fungus has antioxidative, anti-inflammatory and other properties. However, reports about P. linteus application to stroke are still limited. In our study, we had established both in vitro oxygen glucose deprivation (OGD), and reoxygenation (O/R) system to mimic in vivo brain ischemia/reperfusion injury. Our results indicated that P. linteus mycelium extract (PLME) treatment was able to protect PC-12 cells from damage caused by OGD or O/R. (The ratio of cell death was decresed from 70% to 5%). Compared to control, PLME pretreated cells under OGD and O/R conditions significantly upregulated p62, Beclin-1and LC3 I protein expression to maintain autophagy in low dose. Furthermore, PLME could up-regulate apoptosis-related protein Bcl-2 expression and significantly inhibit the activation of pro-casapase 3. We also demonstraeed that PLME was capable to suppress the phosphorylations of JNK and eIF-2α protein to avoid initiatiation of apoptosis. Interestingly, only PLME-pretreated cells could significantly upregulate CHOP protein expression under OGD, however, cell treated with cycloheximde do not effect autophagy-related protein expression, but CHOP. Accrodingly, we suggest that CHOP expression may regulated by other signal pathway (such as p38) and not the dominant regulator controlling autophagy related protein expression. In conclusion, PLME could sustain autophagy, suppress pro-apoptotic pathways and inhibit apoptosis to prevent neuronal-like cells from OGD or O/R-induced cell damage. Therefore, Phellinus linteus may offer a new strategy to prevent stroke in the future.
Published Version
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