howdoesershappen.pptVIP

Endoplasmic Reticulum Stress (ERS) and Diabetes Mellitus Outline What is ERS ? Why is ERS ? When does ERS happen ? Where does ERS happen ? How does ERS happen ? What is ERS ? The lumen of the ER provides a specialized environment for posttranslational modification and folding of secreted, transmembrane, and resident proteins of the various compartments of the endomembrane system. Disequilibrium  between ER load and folding capacity Cell adaptation Unfolded protein response (UPR) Why is ERS ? Something wrong with gene (blueprint) means mutation. Something wrong with protein (manufacture) means ERS When does ERS happen ? Lead to ERS Anything cause Inhibition of protein glycosylation, Reduction of formation of disulfide bonds, Calcium depletion from the ER lumen, Impairment of protein transport from the ER to the Golgi, Expression of malfolded proteins, etc Where does ERS happen ? Cystic fibrosis (connective tissue); Hemophilia (blood); Adiposis hepatica (liver); Coronary artery disease (heart); Alzheimers disease (brain). Diabetes: ? cell liver Perphery adipose muscle How does ERS happen ? Hand 1 PERK/BIP-eIF2---translation attenuation ---ATF4 Pancrea ER kinase. or Pancreatic enriched kinase，PEK PERK is a type I transmembrane serine/threonine kinase localized in the ER. Like IRE1α, activation of PERK is triggered by the dissociation of Bip from its ER lumenal domain and this leads to oligomerization and trans-autophosphorylation. The protein kinase PERK couples protein folding in the endoplasmic reticulum (ER) to polypeptide biosynthesis by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (eIF2alpha), attenuating translation initiation in response to ER stress. The exocrine and endoc