信号转导与心血管疾病.pptxVIP

细胞信号转导系统概述;细胞信号转导系统(signal transduction system)由受体或其他可接受信号的分子、细胞内的信号转导通路及其作用的终端所组成。 意义 对认识细胞在生命活动各方面的表现和调控方式，理解生命活动的本质，在分子水平认识各种疾病的发病机制等都有重大意义。;细胞通讯;; 信号转导 （signal transduction）： 指外界信号（如光、电、化学分子）与细胞细胞表面受体作用，通过影响细胞内信使的水平变化，进而引起细胞应答反应的一系列过程。;细胞信号传导的基本过程和机制;信号分子;信号分子;化学信号的作用方式：;;;;细胞信号传导的基本过程和机制;1、启始 配体与受体结合，启动膜内侧级联反应，将信号传给第二信使分子。 2、转导（放大和整合） 多种信使分子通过不同通路激活一系列蛋白激酶传导信息，实现信号的放大与整合。 3、细胞反应（效应） 信号分子或转录因子进入细胞核，与基因相互作用，调节蛋白质合成或细胞分泌、运动、形态变化和凋亡。 4、中止 通过负反馈途径，活化抑制因子或灭活因子，终止信号的启动作用。;Cross-Talk;细胞信号转导大事记;Dr. Janeway. ;Abbreviations: TLRs (Toll-like receptors) TIR (Toll/IL-1 resistance) MyD88 (Myeloid Differentiation protein-88 ） MAL (MyD88-adapter-like; also known as TIRAP) TIRAP(TIR domain containing adaptor protein) IRAK (IL-1 receptor-associated kinase) TRAF6 (TNF receptor-associated factor 6) TAK-1(TGFβ-activated kinase-1) TAB2 (TAK1 binding protein 2) TRIF (TIR-domain-containing adapter protein inducing interferon-β ) TRAM (TRIF-related adapter molecule) TICAM-1(TIR domain containing adaptor molecular 1) Tollip (Toll-interacting protein) PAMP (pathogen associated molecular pattern) HSP (heat shock protein) IRF (interferon regulatory factor );TLRs structure include a LRR and a TIR domain;Ligand specificities of mammalian TLRs ;;MyD88 has a Death domain (DD);TLR Signaling Pathways;;;;;第三节 TLRs信号通路与心血管疾病;Atherosclerosis and inflammation;Recently, a possible role for TLR4 signaling in arterial remodeling has been revealed in mouse models. ; MyD88 and TLR4 deficiency reduces the extent of aortic atherosclerosis;Lipid content, macrophage infiltration, and COX-2 expression in aortic sinus plaques is reduced in Apoe-/-MyD88-/-mice.;Macrophage infiltration in aortic sinus plaques;COX-2 expression in aortic sinus plaques;Serum concentration of IL-12p40 and MCP-1 are reduced in Apoe-/-MyD88-/-mice.;;Increased inflammatory cytokine (TNFα, IL-1β and IL-6) expression have been found in CHF and ischemic hearts.;;;;;;;;;A20 Is Dynamic