自嗜综述-j.pptVIP

Crosstalk Between Autophagy and Apoptosis in Heart Disease Circulation Research August 15, 2008 IF: 9.721 Apoptosis Characteristic changes: Chromatin condensation and fragmentation Cell shrinkage plasma membrane blebbing apoptotic body formation Apoptosis autophagy Macroautophagy Microautophagy chaperon mediated autophagy, CMA Autophagy is controlled by artophagy-realated gens(Atg). Atg12-Atg5、Atg8 (LC3)–phosphatidylethanolamine Autophagy typeⅢ PI3-kinase complex Physiological and pathophysiological roles in artophagy. Adaptation to nrtrient deprivation intracellular clearance of protein and organelles Antiaging elimination of microorganisms cell death tumor suppression antigen presentation Autophagy as a Cell Survival Mechanism Autophagy as a Cell Death Mechanism Molecular Mechanisms of Crosstalk Between Autophagy and Apoptosis Relationship Between Autophagy and Apoptosis in Heart Disease Autophagy as a Cell Survival Mechanism Beclin 1-/- mice are embryonic lethal at 7.5 to 8.5 days of embryogenesis. Beclin 1 +/- mice experience a high incidence of spontaneous tumors that express wild-type beclin 1 mRNA and protein To examine the role of autophagy under normal conditions,mice with tissue-specific Atg-deficiency were developed. When autophagy is enhanced, cell death mediated by apoptosis is inhibited. Glyceraldehyde-3-phosphate dehydrogenase enhances autophagy and preserves survival after apoptotic cytochrome c release in the absence of caspase activation. When autophagy is induced by inhibition of mTOR, toxicity of polyglutamine expansions is reduced in fly and mouse models of Huntington’s disease. Because many types of cellular stresses trigger apoptoticcell death, the prosurvival role of autophagy is evident in cells that lack the apoptotic pathway. Autophagy removes not only harmful protein aggregates but also harmful organelles, such as mitochondria and endoplasmic reticulum (ER). Autophagy as a Cel