微RNA-133和心肌肥厚钙调磷酸酯酶控制的相互抑制(英文)课件.ppt
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- 关 键 词:
- RNA 133 心肌 肥厚 磷酸酯 控制 相互 抑制 英文 课件
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1、Reciprocal Repression between MicroRNA-133 and Calcineurin Controls Cardiac Hypertrophy:A Novel Mechanism for Progressive Cardiac HypertrophyDe-Li Dong,Yan-Jie Lu,Bao-Feng Yang(董德利董德利 吕延杰吕延杰 杨宝峰杨宝峰)Department of PharmacologyHarbin Medical University,P.R.China Aug.20-22,2009.Dalian BackgroundoCalcine
2、urin/NFAT pathway induces Cardiac Hypertrophy oCalcineurin activation in cardiac hypertrophyoDecreased miR-133 expression in cardiac hypertrophy oOverexpression of miR-133 inhibits cardiac hypertrophy oInhibition of miR-133 induces cardiac hypertrophyAug.20-22,2009.Dalian 1.Calcineurin-Dependent Car
3、diac HypertrophyJeffery D.Molkentin et al.Cell,1998;93,215228.Aug.20-22,2009.Dalian 1.Calcineurin-Dependent Cardiac HypertrophyJeffery D.Molkentin et al.Cell,1998;93,215228.Aug.20-22,2009.Dalian 1.Calcineurin-Dependent Cardiac HypertrophyJeffery D.Molkentin et al.Cell,1998;93,215228.Aug.20-22,2009.D
4、alian Overexpression of calcineurin in mouse causes sudden cardiac death associated with decreased density of K channelsDeli Dong.et al.Cardiovascular Research 57(2003)320332Aug.20-22,2009.Dalian 2.Calcineurin Activation in cardiac hypertrophyHae W.Lim et al.Circulation.2000;101:2431-2437.Aug.20-22,
5、2009.Dalian 3.Calcineurin/NFAT Coupling Participates in Pathological,butnot Physiological,Cardiac HypertrophyWilkins BJ,et al.Circ Res.2004;94:110-118.Aug.20-22,2009.Dalian Car A et al.Nat Med.2007;13(5):613-8.4.Decreased miR-133 expression in cardiac hypertrophyAug.20-22,2009.Dalian 5.Overexpressio
6、n of miR-133 inhibits cardiac hypertrophyCar A et al.Nat Med.2007;13(5):613-8.Aug.20-22,2009.Dalian 6.Inhibition of miR-133 induces cardiac hypertrophyCar A et al.Nat Med.2007;13(5):613-8.Aug.20-22,2009.Dalian Hypothesis:Interaction between miR-133 and calcineurin in cardiac hypertrophy?Calcineurin
7、is the target of miR-133;The expression of miR-133 is regulated by calcineurin/NFAT signaling pathway.CalcineurinmiR-133Cardiac hypertrophyAug.20-22,2009.Dalian Results 1.miR-133 Targets Calcineurin Figure 1.Post-transcriptional Repression of Calcineurin by miR-133.(A)The sequences showing the uniqu
8、e sites of miRNA:mRNA complementary between miR-133 and calcineurin for rat and mouse genes.(B)Co-transfection of miR-133 with the luciferase reporter gene linked to the 3UTR of calcineurin reduced luciferase activity in rat and mouse species.*P0.01 vs Control;#P0.05 vs miR-133.00.51.0 Relative luci
9、ferase activity 00.51.0NCmiR-133+AMO-133miR-133AMO-133Mut-133*#*BMouse(n=8)Rat(n=10)5-UUGGUCCCCUUCAACCAGCUGU-3mmu-miR-133a/rno-miR-133aRat PP2B 3UTR(NM_017042)Rat miR-1333-UGUCGACCAACUUCCCCUGGUU-51600-AACCAUAGUGCCCAGUGACCAG-1621 2225-UGAACAAGAUCCAAAAAACCAA-22463-UGUCGACCAACUUCCCCUGGUU-5Rat PP2B 3UTR
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