The Impact of GSK-3β on the Replication of Influenza Virus in A549 Cells

作者: 戴新宪 :北京生物制品研究所有限责任公司,北京; 张丽姝 , 韩鸿雅 :北京交通大学理学院,北京;

关键词: 病毒学流感病毒细胞凋亡糖原合成激酶-3β病毒与宿主相互作用Virology Influenza Virus Cell Apoptosis Glycogen Synthase Kinase-3β Viral-Host Interaction


Abstract: Objective: In order to clarify the role of glycogen synthase kinase-3β (GSK-3β) in the process of influenza virus infection. Methods: We preformed the RNAi to knock down the GSK-3β gene expression, then we determined the virus titers in the A549 cell supernatants by performing TCID 50 assay, and examined the influence of GSK-3β to cell viabilities of the infected cells as well as the influenza virus-induced A549 cell apoptosis using CCK-8 Kit and Caspase-Glo 3/7 Kit. Results: The results demonstrated that down-regulation of GSK3 expression decreased the viral titers in the A549 cells supernatants. Down-regulation of GSK-3β expression decreased the A549 cell viability, at the same time, increased the influenza virus induced cell apoptosis. Conclusion: Hence, GSK-3β negatively regulated the influenza virus-induced host cell apoptosis, and it was essential for the efficient replication of influenza virus.


文章引用: 戴新宪 , 张丽姝 , 韩鸿雅 (2016) GSK-3β对流感病毒在A549细胞中复制的影响。 自然科学, 4, 371-377. doi: 10.12677/OJNS.2016.44045


[1] Embi, N., Rylatt, D.B. and Cohen, P. (1980) Glycogen Synthase Kinase-3 from Rabbit Skeletal Muscle. Separation from Cyclic-AMP-Dependent Protein Kinase and Phosphorylase Kinase. European Journal of Biochemistry, 107, 519- 527.

[2] Rylatt, D.B., Aitken, A., Bilham, T., Condon, G.D., Embi, N. and Cohen, P. (1980) Glycogen Synthase from Rabbit Skeletal Muscle. Amino Acid Sequence at the Sites Phosphorylated by Glycogen Synthase Kinase-3, and Extension of the N-Terminal Sequence Containing the Site Phosphorylated by Phosphorylase Kinase. European Journal of Biochemistry, 107, 529-537.

[3] Jope, R.S. and Johnson, G.V. (2004) The Glamour and Gloom of Glycogen Synthase Kinase-3. Trends in Biochemical Sciences, 29, 95-102.

[4] Beurel, E. and Jope, R.S. (2006) The Paradoxical Pro- and An-ti-Apoptotic Actions of GSK3 in the Intrinsic and Extrinsic Apoptosis Signaling Pathways. Progress in Neurobiology, 79, 173-189.

[5] Chin, P.C., Majdzadeh, N. and D’Mello, S.R. (2005) Inhibition of GSK3β Is a Common Event in Neuroprotection by Different Survival Factors. Molecular Brain Research, 137, 193-201.

[6] Shin, S.Y., Kim, C.G., Jho, E.-H., Rho, M.-S., Kim, Y.S., Kim, Y.-H. and Lee, Y.H. (2004) Hydrogen Peroxide Negatively Modulates Wnt Signaling through Downregulation of β-Catenin. Cancer Letters, 212, 225-231.

[7] Srinivasan, S., Ohsugi, M., Liu, Z., Fatrai, S., Bernal-Mizrachi, E. and Permutt, M.A. (2005) Endoplasmic Reticulum Stress-Induced Apoptosis Is Partly Mediated by Reduced Insulin Signaling through Phosphatidylinositol 3-Kinase/Akt and Increased Glycogen Synthase Kinase-3β in Mouse Insulinoma Cells. Diabetes, 54, 968-975.

[8] Watcharasit, P., Bijur, G.N., Song, L., Zhu, J., Chen, X. and Jope, R.S. (2003) Glycogen Synthase Kinase-3β (GSK3β) Binds to and Promotes the Actions of p53. The Journal of Biological Chemistry, 278, 48872-48879.

[9] Watcharasit, P., Bijur, G.N., Zmijewski, J.W., Song, L., Zmijewska, A., Chen, X., Johnson, G.V.W. and Jope, R.S. (2002) Direct, Activating Interaction between Glycogen Synthase Kinase-3β and p53 after DNA Damage. Proceedings of the National Academy of Sciences of the United States of America, 99, 7951-7955.

[10] Song, L., Zhou, T. and Jope, R.S. (2004) Lithium Facilitates Apoptotic Signaling Induced by Activation of the Fas Death Domain-Containing Receptor. BMC Neuroscience, 5, 1-7.

[11] Bournat, J.C., Brown, A.M.C. and Soler, A.P. (2000) Wnt-1 Dependent Activation of the Survival Factor NF-κB in PC12 Cells. Journal of Neuroscience Research, 61, 21-32.<21::AID-JNR3>3.0.CO;2-7

[12] Ciani, L. and Salinas, P.C. (2005) WNTs in the Vertebrate Nervous System: From Patterning to Neuronal Connectivity. Nature Reviews. Neuroscience, 6, 351-362.

[13] Zmijewski, J.W. and Jope, R.S. (2004) Nuclear Accumulation of Glycogen Synthase Kinase-3 during Replicative Senescence of Human Fibroblasts. Aging Cell, 3, 309-317.

[14] Ehrhardt, C., Wolff, T., Pleschka, S., Planz, O., Beermann, W., Bode, J.G., Schmolke, M. and Ludwig, S. (2007) Influenza A Virus NS1 Protein Activates the PI3K/Akt Pathway to Mediate Antiapoptotic Signaling Responses. Journal of Virology, 81, 3058-3067.