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,*,*,汇报人：赵丽,Role of ERO1-,mediated stimulation of inositol,1,4,5-triphosphate receptor activity in endoplasmic,reticulum stressinduced apoptosis,汇报人：赵丽Role of ERO1-mediated,1,Contents,实验目的,2,结果分析,3,研究背景,3,1,实验结论,4,Contents实验目的 2结果分析3研究背景31实验结论4,2,研究背景,Endoplasmic reticulum(ER)stressinduced apoptosis is involved in many diseases,but the mechanisms linking ER stress to apopt-osis are incompletely understood,.,*,CHOP:,增强子结合蛋白（）是应激特异的转录因子,研究背景Endoplasmic reticulum(ER),3,研究背景,CHOP:,正常情况下,表达十分低下，在应激反应时,-,、和的活化均对,O,产生诱导，促使,C,O,激活，其表达显著增加，从而诱导细胞凋亡。,钙离子：从内质网内释放的钙离子可以通过激活钙联蛋白调节的钙调神经磷酸酶，使得前凋亡蛋白（,Bad,）去磷酸化，并使与其抑制蛋白解离，然后转移到线粒体进而激发细胞色素的释放，从而导致细胞的凋亡,研究背景,4,研究背景,Based on roles for C/EPB homologous protein(CHOP)and ER calcium release in apoptosis,we hypothesized that apoptos-is involves the activation of inositol 1,4,5-triphosphate(IP3)receptor(IP3R)via CHOP-induced ERO1-(ER oxidase 1),IP3R:,向胞浆内释放钙离子,Hypothesis,：,CHOP ERO1,IP3R,钙释放 凋亡,*,研究背景Based on roles for C/E,5,研究背景,In ER-stressed cells,ERO1-,is induced by CHOP,and small interfering RNA(siRNA)knockdown of ERO1-,suppresses apoptosis.,2.IP3-induced calcium release(IICR)is increased during ER stress,and this response is blocked by siRNA-mediated silencing of ERO1-,or IP3R1 and by loss-of-function mutations in ERO1 or CHOP.,研究背景In ER-stressed cells,ERO1-,6,研究背景,3.,4.,研究背景 3.4.,7,研究背景,5.,1,2,3,4,5,CHOP ERO1-,/,IP3R calcium-dependent apoptosis,研究背景,8,研究背景,半胱天冬酶（,Caspase,）是近年发现的一组存在于胞质溶胶中的酶，它能特异性的切割蛋白质中天冬氨酸残基后的肽键，使细胞内众多的功能蛋白分子活化或失活，诱导细胞凋亡。,IRE1:,需肌醇酶,研究背景半胱天冬酶（Caspase）是近年发现的一组存在于胞,9,实验目标,ERS/CHOP,通路诱导细胞凋亡模型，关键目标是阐明钙释放的分子机制,验证假说：,ERS CHOP ERO1,IP3R,calcium release,apoptosis,实验目标ERS/CHOP通路诱导细胞凋亡模型，关键目标是阐明,10,实验结果,1.,Role of ERO1-,in ER stressinduced apoptosis in macrophages.,CHOP,对,ERO1,具有诱导作用,实验结果1.Role of ERO1-in ER st,11,1.,Role of ERO1-,in ER stressinduced apoptosis in macrophages.,实验结果,1.Role of ERO1-in ER stress,12,1.,Role of ERO1-,in ER stressinduced apoptosis in macrophages.,ERO1,促进细胞凋亡,实验结果,1.Role of ERO1-in ER stress,13,1.,Role of ERO1-,in ER stressinduced apoptosis in macrophages.,实验结果,ERO1-,is critical for ER stressinduced apoptosis,1.Role of ERO1-in ER stress,14,实验结果,2,.Role of ERO1-,in ER stressinduced activation of IICR.,ERO1-,激活IP3R,诱导的钙释放,实验结果2.Role of ERO1-in ER str,15,实验结果,2,.Role of ERO1-,in ER stressinduced activation of IICR.,实验结果2.Role of ERO1-in ER str,16,实验结果,2,.Role of ERO1-,in ER stressinduced activation of IICR.,ERO1-activates IP3-induced calcium release(IICR)during ER stress,实验结果2.Role of ERO1-in ER str,17,实验结果,3,.Relationships among IP3R1,NAC-inhibitable oxidation,CaMKII phosphorylation,and apoptosis.,实验结果3.Relationships among IP3R,18,实验结果,3,.Relationships among IP3R1,NAC-inhibitable oxidation,CaMKII phosphorylation,and apoptosis.,实验结果3.Relationships among IP3R,19,IP3R1 is necessary for ER stressinduced apoptosis,实验结果,3,.Relationships among IP3R1,NAC-inhibitable oxidation,CaMKII phosphorylation,and apoptosis.,IP3R1 is necessary for ER stre,20,实验结果,4.,Role of CHOP in ER stressinduced IICR.,实验结果4.Role of CHOP in ER stres,21,4.,Role of CHOP in ER stressinduced IICR.,CHOP is necessary for activation of IICR during ER stress in vitro and in vivo,实验结果,4.Role of CHOP in ER stressin,22,实验结果,5,.ER stressinduced IICR in vivo.,实验结果5.ER stressinduced IICR i,23,实验结果,5,.ER stressinduced IICR in vivo.,实验结果5.ER stressinduced IICR i,24,实验结论,ERO1-is critical for ER stressinduced apoptosis,2.ERO1-activates IP3-induced calcium release(IICR)during ER stress,3.IP3R1 is necessary for ER stressinduced apoptosis,4.CHOP is necessary for activation of IICR during ER stress in vitro and in vivo,实验结论ERO1-is critical for ER,25,内质网应激致细胞凋亡课件,26,
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