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PCSK9-siRNA对ox-LDL诱导的THP-1源性巨噬细胞凋亡中Caspase-3表达的影响 被引量:2

EFFECT OF PCSK9-siRNA ON THE EXPRESSION OF Caspase-3 IN ox-LDL-INDUCED THP-1 MACROPHAGE CELLS
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摘要 目的:研究枯草溶菌素转化酶9(PCSK9)-siRNA对ox-LDL诱导的THP-1源性巨噬细胞凋亡中Caspase-3蛋白表达的影响。方法:用不同浓度ox-LDL处理THP-1源性巨噬细胞不同时间,Western blot检测Caspase-3蛋白表达变化。应用Li-pofectamine2000分别转染不同浓度PCSK9-siRNA进THP-1源性巨噬细胞中,作用24 h后加入ox-LDL处理48 h,Westernblot分析细胞Caspase-3蛋白表达。结果:随着ox-LDL浓度的增加,Caspase-3蛋白表达上调,呈浓度依赖性,80 mg/L ox-LDL处理组作用最为明显;80 mg/L ox-LDL处理THP-1源性巨噬细胞不同时间后,Western blot检测发现Caspase-3蛋白表达上调,呈时间依赖性,48 h处理组作用最为明显;PCSK9-siRNA能明显下调Caspase-3蛋白表达,呈浓度依赖性。结论:PC-SK9-siRNA抑制ox-LDL诱导的THP-1源性巨噬细胞凋亡与凋亡执行酶Caspase-3蛋白表达下调有关。 Objective:To demonstate the ffect of PCSK9-siRNA on the expression of Caspase-3 in ox-LDL-induced THP-1 macrophage cells.Methods:Different concentrations of ox-LDL were used to treat THP-1 macrophages at different times.Western blot detected Caspase-3 protein level.Lipofectamine2000 were transfected with different concentrations PCSK9 siRNAs(30,50,80 nmol/L) into THP-1 derived macrophages.After 24 hours,ox-LDL was added for 48 hours,Western blot examined Caspase-3 expression.Results:Ox-LDL increased Caspase-3 protein expression in a dose and time dependent manner.PCSK9-siRNA significantly reduced Caspase-3 protein expression in a dose dependent manner.Conclusion:PCSK9-siRNA inhibited the apoptosis of ox-LDL-induced THP-1 derived macrophages.The mechanism of this action may be related to the downregulation of Caspase-3.
出处 《广西医科大学学报》 CAS 2011年第1期58-61,共4页 Journal of Guangxi Medical University
基金 湖南省应用基础研究计划重点项目(No.2008FJ2006) 湖南省科技厅计划项目(No.2009TP4057-2 2010TP4008-2) 湖南省教育厅重点科研项目(No.10A105) 湖南省高校科技创新团队支持计划资助
关键词 枯草溶菌素转换酶9 巨噬细胞 凋亡 Caspase-3 bacillus bacteriolytic factor-converting enzyme 9 macrophage apoptosis caspase-3
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  • 1程艳丽,谢闵,刘录山,王贵学.pcsk9基因突变与胆固醇血症[J].中国生物化学与分子生物学报,2007,23(3):172-176. 被引量:6
  • 2Elagoz A, Benjannel S, Mammarbassi A, et al. Biosynthesis and cellular trafficking of the convertase SKI-1/SIP: eetodomain shedding requires SKI-1activity. J Biol Chem, 2002, 277 (13): 11265- 11275
  • 3Seidah N G, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated convertase 1 (NARC-1): liver regeneration and neuronal differentiation.Proc Natl Acad Sci USA, 2003, 100(3): 928-933
  • 4Maxwell K N, Fisher E A, Breslow J L, et al. Over expression of PCSK9 accelerates the degradation of the LDLR in a post-endoplasmic reticulum compartment. Proc Natl Acad Sci USA, 2005, 102(6): 2069-2074
  • 5Poirier S, Prat A, Marcinkiewicz E, et al. Implication of the proprotein convertase PCSK9/NARC-1 in the development of the nervous system. J Neurochem, 2006, 98(3): 838-850
  • 6Peterson A S, Fong L G, Young S G. PCSK9 function and physiology. J Lipid Res, 2008, 49(6): 1152- 1156
  • 7Bingham B, Shen R, Kotnis S, et al. Proapoptotic effects ofNARC 1 (= PCSKg), the gene encoding a novel serine proteinase. Cytometry A, 2006, 69(11): 1123-1131
  • 8Brown M S, Goldstein J L. Lowing LDL-not only how low, but how long?. Science, 2006, 311(5768): 1721 - 1723
  • 9Libby P, Geng Y J, Aikawa M, et al. Macrophage and atherosclerotic plaque stability. Curr Opin Lipidol, 1996, 7(5): 330-335
  • 10Boyle J J. Macrophage activation in atherosclerosis: pathogenesis and pharmacology of plaque rupture, Curr Vasc Pharmacol, 2005, 3 (1): 63-68

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  • 1Abifadel M, Guerin M, Benjannet S, et al. Identification and characterization of new gain-of-function mutations in the PCSK9 gene responsible for autosomal dominant hypercholesterolemia[J]. Atheroselerosis, 2012, 223(2) :394- 400.
  • 2Seidah NG, Benjannet S, Wickham L, et al. The secretory proprotein convertase neural apoptosis-regulated eonvertase 1 (NARC-1) :liver regeneration and neuronal differentiationl-J]. Proc Natl Acad Sci U S A, 2003, 100(3):928-933.
  • 3Hassan M, Latif N, Yacoub M. Adipose tissue: friend or foe [J]. Nat Rev Cardiol, 2012, 9(12):689-702.
  • 4Leren TP. Sorting an LDL receptor with bound PCSK9 to intracellular degradationEJ]. Atherosclerosis, 2014, 237 (1) 76-81.
  • 5Roth EM, McKenney JM, Hanotin C, et al. Atorvastatin with or without an antibody to PCSK9 in primary hypercholesterolemia[J]. N Engl J Med, 2012, 367 (20) 1891-1900.
  • 6Lee P, Hegele RA. Current phase ]l proprotein eonvertase subtilisin/kexin 9 inhibitor therapies for dyslipidemia [J]. Expert Opin Investig Drugs, 2013, 22(11) : 1411-1423.
  • 7Corral P. Back to basics: PCSK9 as a new target for the LDL receptor[J]. Arq Bras Cardiol, 2014, 102(1):e5-8.
  • 8Saavedra YG, Zhang J, Seidah NG. PCSK9 prosegmentchimera as novel inhibitors of LDLR degradation[J]. PLoS One, 2013, 8(8) :e72113.
  • 9Benjannet S, Hamelin J, Chr6tien M, et al. Loss-and gain-of- function PCSK9 variants: cleavage specificity, dominant negative effects, and low density lipoprotein receptor (LDLR) degradation[J]. J Biol Chem, 2012, 287(40) :33745-33755.
  • 10Poirier S, Mayer G. The biology of PCSK9 from theendoplasmic reticulum to lysosomes: new and emerging therapeutics to control low-density lipoprotein cholesterol[J]. Drug Des Devel Ther, 2013, 7:1135-1148.

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