汇报汇报人：赵丽赵丽Role of ERO1-mediated stimulation of inositol 1,4,5-triphosphate receptor activity in endoplasmic reticulum stressinduced apoptosisContents实验实验 目的 2结结果分析3研究背景3 1实验结论实验结论4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:增强子结结合蛋白（）是应应激 特异的转录转录因子研究背景CHOP:正常情况下,表达十分低下，在应应激反应时应时, -、和的活化均对对O产产生诱导诱导， 促使CO激活，其表达显显著增加，从而诱导细诱导细胞凋亡。钙钙离子：从内质质网内释释放的钙钙离子可以通过过激活钙联钙联蛋白调节调节的 钙调钙调神经经磷酸酶，使得前凋亡蛋白（Bad）去磷酸化，并使 与其抑制蛋白解离，然后转转移到线线粒体进进而激发细发细胞色素的 释释放，从而导导致细细胞的凋亡研究背景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:向胞浆浆内释释放钙钙离子Hypothesis：CHOP ERO1 IP3R 钙释钙释 放 凋亡*研究背景1. 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3.4.研究背景5.12345CHOP ERO1-/IP3R calcium- dependent apoptosis研究背景半胱天冬酶（Caspase）是近年发现发现 的一组组存在于胞质质溶 胶中的酶，它能特异性的切割蛋白质质中天冬氨酸残基后的肽肽 键键，使细细胞内众多的功能蛋白分子活化或失活，诱导细诱导细 胞 凋亡。IRE1:需肌醇酶实验目标ERS/CHOP通路诱导细诱导细 胞凋亡模型，关键键目标标是阐阐明 钙释钙释 放的分子机制验证验证 假说说：ERS CHOP ERO1 IP3R calcium release apoptosis实验结果1. Role of ERO1- in ER stressinduced apoptosis in macrophages. CHOP对ERO1 具有诱导作用1. Role of ERO1- in ER stressinduced apoptosis in macrophages. 实验结果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 stressinduced apoptosis in macrophages.实验结果ERO1- is critical for ER stressinduced apoptosis实验结果2.Role of ERO1- in ER stressinduced activation of IICR.ERO1-激活IP3R 诱导诱导 的钙释钙释 放实验结果2.Role of ERO1- in ER stressinduced activation of IICR.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3.Relationships among IP3R1, NAC-inhibitable oxidation, CaMKII phosphorylation, and apoptosis. 实验结果3.Relationships among IP3R1, NAC-inhibitable oxidation, CaMKII phosphorylation, and apoptosis. IP3R1 is necessary for ER stressinduced apoptosis实验结果3.Relationships among IP3R1, NAC-inhibitable oxidation, CaMKII phosphorylation, and apoptosis. 实验结果4.Role of CHOP in ER stressinduced IICR. 4.Role of CHOP in ER stressinduced IICR.CHOP is necessary for activation of IICR during ER stress in vitro and in vivo实验结果实验结果5.ER stressinduced IICR in vivo.实验结果5.ER stressinduced IICR in vivo.实验结论1. ERO1- is critical for ER stressinduced apoptosis2. ERO1- activates IP3-induced calcium release (IICR) during ER stress3. IP3R1 is necessary for ER stressinduced apoptosis4. CHOP is necessary for activation of IICR during ER stress in vitro and in vivo