Myrica rubra is well known for its delicious taste and high nutritional value. The present study investigated the potential protective effects and mechanisms of M. rubra flavonoids (MRF) extract on isoproterenol (ISO)-induced myocardial injury in rats and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes. An in vivo study revealed that MRF decreased serum cardiac enzyme levels, ameliorated pathological heart alterations and increased the antioxidant potential. The in vitro investigation demonstrated that MRF inhibited cell death, reactive oxygen species (ROS) accumulation, mitochondrial membrane depolarization, apoptosis rate and caspase-3 activation and enhanced the Bcl-2/Bax ratio during H/R injury. These effects were accompanied by the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase (GSK)-3β. Further mechanism studies demonstrated that LY294002, a specific inhibitor of phosphoinositide 3-kinase (PI3K), abolished the MRF-mediated cardioprotection against H/R-induced apoptosis and ROS overproduction. Collectively, these results suggested that MRF exerts cardioprotective effects by attenuating oxidative damage and cardiomyocyte apoptosis most likely via a PI3K/Akt/GSK3β-dependent mechanism.
The present study investigated the role of cytochrome P450 family 2 subfamily e polypeptide 1 (cYP2e1) in the development and progression of gastric cancer (Gc). The expression levels of cYP2e1 in MGc-803 Gc cells and normal GeS-1 cells were investigated via western blotting, and it was identified that the expression of CYP2E1 was different between GeS-1 and MGc-803 cells. cYP2e1 was overexpressed in MGc-803 cells using a lentiviral vector GV358. cell counting Kit-8, flow cytometry, cell migration and Matrigel invasion assays suggested that overexpression of cYP2e1 promoted the proliferation and invasion, and inhibited the apoptosis of Gc cells. The relationship between cYP2e1 expression and key signaling molecules in the Pi3K/akt/mTor signaling pathway was assessed. reverse transcription-quantitative Pcr analysis showed that mTor mrna expression was significantly increased after overexpression of cYP2e1 (P<0.05). Western blotting results showed that overexpression of cYP2e1 upregulated the expression of phosphorylated (p)-akt, p-mTor and p-p70 ribosomal protein S6 kinase (P70S6K; Ser371) proteins (P<0.05). To further investigate the relationship between cYP2e1 and the Pi3K/akt/mTor signaling pathway in Gc cells, MGc-803 cells were treated with the Pi3K inhibitor lY294002, and changes in the expression levels of Pi3K, aKT, mTor, P70S6K and cYP2e1 were observed. The present results showed that lY294002 downregulated the expression of Pi3K, cYP2e1, aKT, mTor and P70S6K (P<0.05). Therefore, changes in the biological function of Gc cells induced by cYP2e1 overexpression may be via the Pi3K/akt/mTor signaling pathway.
In mammals, neurons in the central nervous system (CNS) lose their axon growth ability as they mature. On the contrary, mature neurons in the peripheral nervous system (PNS) still possess such an ability and can spontaneously regenerate axons upon axonal injury by initiating a regenerative response. Emerging evidence suggests that the transition from a non‐regenerative state to a regenerative state of injured PNS neurons largely involves epigenetic regulation of chromatin accessibility. Here we investigated the role of Ezh2, a histone methyltransferase that adds methyl groups onto lysine 27 on histone H3 (H3K27) to suppress gene transcription, in mammalian axon regeneration. Western blot results showed that Ezh2 level was significantly upregulated in mouse lumbar 4 and 5 dorsal root ganglia (L4/5 DRGs) 3 days following sciatic nerve axotomy. Functionally, Ezh2 knockdown or knockout in cultured DRG neurons impaired axon growth in vitro. In consistence, knockdown or knockout of Ezh2 in L4/5 DRGs by in vivo electroporation or conditional knockout of Ezh2 in sensory neurons impaired sensory axon regeneration after sciatic nerve crush. More importantly, using optic nerve regeneration model, we found that overexpressing Ezh2 in retinal ganglion cells (RGCs) by intravitreal injection of AAV2‐Ezh2 virus significantly promoted axon regeneration after optic nerve crush. RNA‐seq analysis of RGCs enriched by fluorescence‐activated cell sorting revealed that the transcription of a large number of genes involved in synaptic transmission were downregulated by Ezh2 overexpression, indicating that Ezh2 supports axon regeneration by rejuvenating adult neurons to a younger state. Using optic nerve regeneration model again, we showed that overexpression of Slc6a13 (encoding Gat2), a gene suppressed by Ezh2, partially blocked RGC axon regeneration induced by Ezh2 overexpression. Our study demonstrated that Ezh2 was required for the successful spontaneous axon regeneration in the PNS, and that Ezh2 gain‐of‐function could promote axon regeneration in the CNS by silencing synaptic transmission‐associated genes.
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