内质网应激与细胞凋亡.pptxVIP

徐悦蓉 孙嘉星 丁家琦 孔静 俞正 钮春子Endoplasmic Reticulum Stress and Apoptosis TEAMWORK钮春子 丁家琦 孔静 俞正 孙嘉星 徐悦蓉CATALOGUEEndoplasmic Reticulum (ER) The endoplasmic reticulum(ER) is a multifunctional organelle with in which protein folding, lipid biosynthesis, and calcium storage occurs.Endoplasmic Reticulum StressVarious factors that interfere with ER function lead to accumulation of unfolded proteins, including oxidative stress, ischemia, disturbance of calcium homeostasis, and over expression of normal and/or incorrectly folded proteins. This process is called ER stress and further activates the unfolding protein response (UPR).MAJOR FACTERSUPR(unfolded protein response)IRE-1(inositol requiring element-1)PERK(PKR-like ER kinase)ATF6(activating transcription factor 6)GPR78/BIP(glucose-regulated protein 78/binding immunoglobulin protein)CHOP (C/EBP homologous protein )Bak/Bax (Bcl-2 family members )Caspase-12AKS1(apoptosis-signal regulating kinase) JNK (c-Jun NH2-terminal kinase )TextIRE-1mediateBIPATF6TextPERKUPRUPRER STRESS RESPONSE SIGNALIRE-1ATF63 PROXIMAL SENSORSPERKEndoplasmic Reticulum StressER Stress and Apoptosis SUSTAINED ER STRESS LEADS TO AN INFLAMMATORY RESPONSE AND APOPTOSISER Stress and Apoptosis CHOPASK1/JNKPERK ATF6 IRE-1PERK-elF2α-ATF4TRB3 AKTBCL-2 familyIRE-1IRE-1-TRAF2-ASK1JNKBCL-2CaspasesBcl-2 Family ProteinCa2+→calpain→Caspase-12TRAF2 procaspase-12→Caspase-12Caspase-7→Caspase-12Caspase-12→Caspase-9 →Caspase-3CHOP JNKBCL-2 Bax BakMitochondrionER Ca2+ ER Stress and Apoptosis Related DiseasesREVIEWREFERENCESThe endoplasmic reticulum stress response in aging and age-related diseases (MarishkaK. Brownand Nirinjini Naidoo*, Center for Sleep and Circadian Neurobiology, University of Pennsylvania, Philadelphia,PA,USA)The Role of Glucosamine-Induced ER Stress in Diabetic Atherogenesis（Daniel R. Beriault and Geoff H.Werstuck， Hindawi Publishing Corporation，Experimental Diabetes Research，Volume 2012, Article ID 187018