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缺氧对稳定表达人淀粉样前体蛋白HEK293细胞的存活及阿尔茨海默病相关蛋白表达的影响 被引量:1

Effects of hypoxia on the survival and Alzheimer's disease-related protein expression in HEK293 cells stably expression APP695 protein
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摘要 目的:探讨缺氧对稳定表达人淀粉样前体蛋白的HEK293细胞(HEK293-APP695)存活及相关蛋白表达的影响,为深入研究缺氧对阿尔茨海默病的调节作用提供稳定的细胞模型。方法:利用缺氧手套箱(0.3%O2)处理HEK293-APP695细胞,CCK-8法检测细胞的存活情况;Western blot检测缺氧条件下阿尔茨海默病(AD)相关蛋白APP、APP-CTFs和BACE1的表达变化。结果:缺氧处理后,HEK293-APP695细胞的存活率明显下降,APP表达降低,其剪切体APP-CTFs表达升高。结论:缺氧导致APP剪切的增多,抑制细胞的存活,提示缺氧可能通过影响BACE1的活性在AD的发病进程中起重要的调节作用。 Objective: To further study the regulation of hypoxia on Alzheimer's disease (AD) pathogenesis, we investigate the effect of hypoxia on the effect of cell survival and expression of related proteins in HEK293 cells stably expressing APP695 Swedish mutantK595N/M596L (HEK293-APP695 cells). Methods: HEK293-APP695 cells were cultured at hypoxia condition (0.3% 02). The survival rate of HEK293- APP695 cells was measured by CCK-8 assay. The protein expression levels of APP, APP-CTFs and BACE1 were detected by Western blot. Results: The survival of HEK293-APP695 cells was obviously decreased after exposed to hypoxia. The expression of APP was reduced, and the expression of APP-CTFs was increased under hypoxia. Conclusion: Our data indicate that hypoxia accelerated cell death of HEK293- APP695 cells by increasing the cleavage of APP and production of β-secretase (β-site amyloid precursor protein cleavage enzymel, BACE1 ).
出处 《中国应用生理学杂志》 CAS CSCD 2016年第2期106-109,共4页 Chinese Journal of Applied Physiology
基金 国家973计划资助项目(2011CB910800 2012CB518200)
关键词 阿尔茨海默病 缺氧 HEK293细胞 淀粉样前体蛋白 Alzheimer' s disease hypoxia HEK293-APP695 APP
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参考文献11

  • 1Huang Y, Mucke L. Alzheimer mechanisms and therapeutic strategies [J]. Cell, 2012, 148(6): 1204-1222.
  • 2王利利,纳鑫,朱小南,陈汝筑,汪海,汪雪兰.Tau/APP/PS1三转基因小鼠模型的建立及生物学特征[J].中国应用生理学杂志,2012,28(4):294-297. 被引量:16
  • 3Matsuda T, Abe T, Wu JL, eta/. Hypoxia-inducible factor- lalpha DNA induced angiogenesis in a rat cerebral ischemia model [J].Neurol Res, 2005, 27(5): 503-508.
  • 4Zhang X, Zhou K, Wang R, eta!. Hypoxia-inducible factor 1 alpha ( HIF- 1 alpha )-mediated hypoxia increases BACE 1 ex- pression and beta-amyloid generation [ J ]. J Biol Chem, 2007, 282(15) : 10873-10880.
  • 5Peers C, Pearson HA, Boyle JP. Hypoxia and Alzheimer' s disease [J]. Essays Biochem, 2007, 43: 153-164.
  • 6Sun X, He G, Qing H, et d. Hypoxia facilitates Alzheimer's disease pathogenesis by up-regulating BACE1 gene expression [J]. Proc Natl Acad Sci U S A, 2006, 103(49): 18727- 18732.
  • 7Fang H, Zhang LF, Meng Fr, et al. Acute hypoxia promote the phosphorylation of tau via ERK pathway [ J]. Neurosci Lett, 20101 474(3): 173-177.
  • 8Wen Y, Yang S, Liu R, eta/. Transient cerebral ischemia induces aberrant neuronal cell cycle re-entry and Alzheimer' s diseas~like tauopathy in female rats [ J]. J Biol Chem, 2004, 279(21): 22684-22692.
  • 9Marshall AJ, Rattray M, Vaughan PF. Chronic hypoxaa m the human neuroblastoma SH-SY5Y causes reduced expres- sion of the putative alpha-secretases, ADAM10 and TACE, without altering their mRNA levels [ J ]. Brain Res, 2006, 12(1) : 18-24.
  • 10Li L, Zhang X, Yang D, et al. Hypoxia increases Abeta generation by altering beta- and gamma-cleavage of APP [J]. Neurobiol Ag/ng, 2009, 30(7) : 1091-1098.

二级参考文献8

  • 1LaFefla F M. Pathways linking Abeta and tau pathologies[J]. Biochem Soc Traas, 2010, 38(4): 993-995.
  • 2Schaeffer E L, Figueiro M, Gattaz W F. Insights into Alzheimer disease pathogenesis from studies in transgenic an- imal models [J]. Cncs, 2011, 66(S1): 45-54.
  • 3Jankowsky J L, Slant H H, Ratovitski T, et al. Coesion of multiple transgenes in mouse CNS: a comparison of strategies [J]. Biomol Eng, 2001, 17(6) : 157-165.
  • 4Wengenack T M, Whelan S, Curran G L, at al. Quantitative histological analysis of amyloid deposition in Alzheimer' s double transgenic mouse brain[J]. Neurosci, 2000, 101 (4) : 939-944.
  • 5Lewis J, Dickson D W, Lin W L, et al. Enhanced neurofib- rillary degeneration in transgenic mice expressing mutant tau and APP[J]. Sd, 2001, 293(5534): 1487-1491.
  • 6Oddo S, Caccamo A, Kitazawa M, a al. Amyloid deposition precedes tangle formation in a triple transgenic model of Alzheimer's disease [J]. NeurobiolAging, 2003, 24(8): 1063-1070.
  • 7Braidy N, Mufioz P, Palacios A G et al. Recent rodent mod- els for Alzheimer' s disease: clinical implications and basic research [J]. J Neural Transm, 2012, 119(2): 173-195.
  • 8王艳艳,陈汝筑,朱小南,刘静,刘秀娟,李志慧,纳鑫,梁珊珊,邱国光,张薇,汪海,汪雪兰.含P301L突变的Tau转基因小鼠纯合子品系的建立及鉴定[J].中国应用生理学杂志,2012,28(3):221-224. 被引量:5

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