Objective:To investigate the vasculogenic mimicry formation induced by hypoxia in Ⅱ-Ⅲ human glioma cell and the effect of alphastatin peptide suppressing the hypoxia-induced vasculogenic mimicry formation and the me...Objective:To investigate the vasculogenic mimicry formation induced by hypoxia in Ⅱ-Ⅲ human glioma cell and the effect of alphastatin peptide suppressing the hypoxia-induced vasculogenic mimicry formation and the mechanism.Methods:MTT,Transwell and three-dimentional culture were used to detect the proliferation,migration and tubule formation of SHG44.The expression of vascular endothelial growth factor-α(VEGF-α),erythropoietin-producing hepatocellular carcinoma-A2 (EphA2) and matrix metalloproteinases 2 (MMP2) was detected by RT-PCR and Western blotting analysis.Results:The OD 490 in hypoxia group was 0.60±0.06 and in control group was 0.46±0.05.The number of cell migration was 178.71±18.81 in hypoxia group and 85.86±17.92 in control group.The tubule formation was 56.80±12.21 in hypoxia group and 4.20±2.62 in control group.The proliferation,migration and tubule formation in hypoxia group were significantly higher than that in control group.The expression of VEGF-α,EphA2 and MMP2 was upregulated in hypoxia.When various concentrations of alphastatin (100,1 000,10 000 nmol/L) were added to hypoxia group,the numbers of cell migration were 142.57±12.12,92.71±17.68,30.00±7.72 and the tubule formation were 47.71±10.58,18.86±8.40,8.43±5.62.The cell migration and tubule formation were significantly suppressed by alphastatin in a dose-dependent manner.In alphastatin group,the phosphorylation of EphA2 protein (P=0.037,F=4.629) and activation of MMP2 protein (P=0.005,F=9.331) were significantly suppressed but there was no change in VEGF-α protein.Conclusion:Ⅱ-Ⅲ human glioma cell is able to form vasculogenic mimicry induced by hypoxia and alphastatin peptide can suppress the hypoxia-induced vasculogenic mimicry.VEGF-α induced EphA2 phospharilation and MMP2 activation maybe the key pathway to form vasculogenic mimicry.展开更多
Aluminium is widely used as an antimicrobial coagulant,food additive,and cookware.However,many reports indicate that aluminium may be a critical factor in many amyloid diseases,such as Alzheimer’s disease and Parkin...Aluminium is widely used as an antimicrobial coagulant,food additive,and cookware.However,many reports indicate that aluminium may be a critical factor in many amyloid diseases,such as Alzheimer’s disease and Parkinson’s disease.Unfortunately,the underlying mechanism is still poorly understood,which limits efforts to prevent and treat these diseases.In this paper,using an ab initio method,we studied the interaction of Al-backbone ring structure with theπ-electron-rich sidechains of His,Phe,Trp,and Tyr.We found that in the absence of water,the Al-backbone ring can stably bind with those sidechains.In the presence of water,the Al-backbone ring can bind to the His sidechain and cannot bind to the other sidechains.As revealed by further investigations,this could be attributed to the fact that there was a coordinate bond of the Al-backbone ring with the His sidechain,while there were theπ-πstacking and cation-π-like interactions with the other sidechains.These findings potentially provide a molecular understanding of Al-related toxicity,and may be helpful in designing drugs for those aforementioned aluminum-linked diseases and encourage treatment of Al-polluted water.展开更多
基金Supported in Part by a Grant from the National Nature Science Foundation of China(No.30672126)
文摘Objective:To investigate the vasculogenic mimicry formation induced by hypoxia in Ⅱ-Ⅲ human glioma cell and the effect of alphastatin peptide suppressing the hypoxia-induced vasculogenic mimicry formation and the mechanism.Methods:MTT,Transwell and three-dimentional culture were used to detect the proliferation,migration and tubule formation of SHG44.The expression of vascular endothelial growth factor-α(VEGF-α),erythropoietin-producing hepatocellular carcinoma-A2 (EphA2) and matrix metalloproteinases 2 (MMP2) was detected by RT-PCR and Western blotting analysis.Results:The OD 490 in hypoxia group was 0.60±0.06 and in control group was 0.46±0.05.The number of cell migration was 178.71±18.81 in hypoxia group and 85.86±17.92 in control group.The tubule formation was 56.80±12.21 in hypoxia group and 4.20±2.62 in control group.The proliferation,migration and tubule formation in hypoxia group were significantly higher than that in control group.The expression of VEGF-α,EphA2 and MMP2 was upregulated in hypoxia.When various concentrations of alphastatin (100,1 000,10 000 nmol/L) were added to hypoxia group,the numbers of cell migration were 142.57±12.12,92.71±17.68,30.00±7.72 and the tubule formation were 47.71±10.58,18.86±8.40,8.43±5.62.The cell migration and tubule formation were significantly suppressed by alphastatin in a dose-dependent manner.In alphastatin group,the phosphorylation of EphA2 protein (P=0.037,F=4.629) and activation of MMP2 protein (P=0.005,F=9.331) were significantly suppressed but there was no change in VEGF-α protein.Conclusion:Ⅱ-Ⅲ human glioma cell is able to form vasculogenic mimicry induced by hypoxia and alphastatin peptide can suppress the hypoxia-induced vasculogenic mimicry.VEGF-α induced EphA2 phospharilation and MMP2 activation maybe the key pathway to form vasculogenic mimicry.
基金Supported by National Natural Science Foundation of China(Nos.11174310 and 11290164)the Key Research Program of Chinese Academy of Sciences(No.KJZD-EW-M03)
文摘Aluminium is widely used as an antimicrobial coagulant,food additive,and cookware.However,many reports indicate that aluminium may be a critical factor in many amyloid diseases,such as Alzheimer’s disease and Parkinson’s disease.Unfortunately,the underlying mechanism is still poorly understood,which limits efforts to prevent and treat these diseases.In this paper,using an ab initio method,we studied the interaction of Al-backbone ring structure with theπ-electron-rich sidechains of His,Phe,Trp,and Tyr.We found that in the absence of water,the Al-backbone ring can stably bind with those sidechains.In the presence of water,the Al-backbone ring can bind to the His sidechain and cannot bind to the other sidechains.As revealed by further investigations,this could be attributed to the fact that there was a coordinate bond of the Al-backbone ring with the His sidechain,while there were theπ-πstacking and cation-π-like interactions with the other sidechains.These findings potentially provide a molecular understanding of Al-related toxicity,and may be helpful in designing drugs for those aforementioned aluminum-linked diseases and encourage treatment of Al-polluted water.
