Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage(SAH).Recently,HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells c aused by carbon io...Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage(SAH).Recently,HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells c aused by carbon ion radiation through activation of the Wnt/β-catenin pathway.This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH.The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6(LRP6),which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta(p-GSK3β)(Ser9),β-catenin,and Bcl-2,accompanied by a decrease of p-β-catenin,Bax,and cleaved caspase 3.An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78.In conclusion,HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats.HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.展开更多
The health-related effects of ionizing radiation on embryonic development and their underlying mechanisms are still unclear.The aim of this study was to investigate the role of Wnt signaling in mediating the developme...The health-related effects of ionizing radiation on embryonic development and their underlying mechanisms are still unclear.The aim of this study was to investigate the role of Wnt signaling in mediating the developmental toxicity induced by heavy ion and proton radiation using zebrafish embryos.Wnt signaling is a well-known cell signaling pathway with roles in embryogenesis.Wnt family members can regulate cell fate determination,differentiation,proliferation,and apoptosis during embryonic development[1;2].Zebrafish embryos were radiated with carbon ions or protons.HLY78,an activator of the Wnt signaling pathway,was added immediately after radiation.Carbon ion radiation induced a significant increase of mortality,and activating Wnt signaling using HLY78 after radiation significantly alleviated this stress.Both carbon ion and proton radiation significantly increased malformation rates and decreased hatching rates.Supplementation with HLY78 significantly reduced the effects induced by carbon ion radiation alone(Fig.1).After irradiation with carbon ions,embryos showed a significant decrease in heart rate,spontaneous movement,and locomotive behavior(Figs.2 and 3).Supplementation with HLY78 was able to reduce these effects.The results of this study improve our understanding of the mechanisms of carbon ion radiation-induced developmental toxicity,which potentially involves the inhibition of Wnt signaling.展开更多
基金This work was supported by the National Natural Science Foundation of China(81771961 and 81401505)the Kuanren Talents Program of the Second Affiliated Hospital of Chongqing Medical University(201959).
文摘Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage(SAH).Recently,HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells c aused by carbon ion radiation through activation of the Wnt/β-catenin pathway.This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH.The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6(LRP6),which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta(p-GSK3β)(Ser9),β-catenin,and Bcl-2,accompanied by a decrease of p-β-catenin,Bax,and cleaved caspase 3.An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78.In conclusion,HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats.HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.
基金Key Program of National Natural Science Foundation of China(U1432248),National Natural Science Foundation of China(11305226)。
文摘The health-related effects of ionizing radiation on embryonic development and their underlying mechanisms are still unclear.The aim of this study was to investigate the role of Wnt signaling in mediating the developmental toxicity induced by heavy ion and proton radiation using zebrafish embryos.Wnt signaling is a well-known cell signaling pathway with roles in embryogenesis.Wnt family members can regulate cell fate determination,differentiation,proliferation,and apoptosis during embryonic development[1;2].Zebrafish embryos were radiated with carbon ions or protons.HLY78,an activator of the Wnt signaling pathway,was added immediately after radiation.Carbon ion radiation induced a significant increase of mortality,and activating Wnt signaling using HLY78 after radiation significantly alleviated this stress.Both carbon ion and proton radiation significantly increased malformation rates and decreased hatching rates.Supplementation with HLY78 significantly reduced the effects induced by carbon ion radiation alone(Fig.1).After irradiation with carbon ions,embryos showed a significant decrease in heart rate,spontaneous movement,and locomotive behavior(Figs.2 and 3).Supplementation with HLY78 was able to reduce these effects.The results of this study improve our understanding of the mechanisms of carbon ion radiation-induced developmental toxicity,which potentially involves the inhibition of Wnt signaling.
