课件：血管内皮细胞凋亡机制.pptVIP

细胞凋亡的检测方法 APOPTOSIS: control Receptor pathway (physiological): Death receptors: (FAS, TNF-R, etc) FAS ligand TNF Death domains Adaptor proteins Pro-caspase 8 (inactive) Caspase 8 (active) Pro-execution caspase (inactive) Execution caspase (active) Death MITOCHONDRIA APOPTOSIS: control Intrinsic pathway (damage): Mitochondria Cytochrome c release Pro-caspase 9 cleavage Pro-execution caspase (3) cleavage Caspase (3) cleavage of cellular proteins, Nuclease activation, Etc. Death BAX BAK BOK BCL-Xs BAD BID B IK BIM NIP3 BNIP3 BCL-2 BCL-XL BCL-W MCL1 BFL1 DIVA NR-13 Several viral proteins APOPTOSIS: control Physiological Intrinsic receptor pathway damage pathway MITOCHONDRIAL SIGNALS Caspase cleavage cascade Orderly cleavage of proteins and DNA CROSSLINKING OF CELL CORPSES; ENGULFMENT (no inflammation) APOPTOSIS: Role in Disease TOO MUCH: 组织萎缩 TOO LITTLE: 增生 Neurodegeneration Thin skin etc Cancer Athersclerosis etc APOPTOSIS: Role in Disease Neurodegeneration Neurons are post-mitotic (cannot replace themselves) Neuronal death caused by loss of proper connections, loss of proper growth factors (e.g. NGF), damage (especially oxidative damage) Neuronal dysfunction or damage results in loss of synapses (synaptosis; reversible) apopsosis (irreversible) PARKINSONS DISEASE ALZHEIMERS DISEASE HUNTINGTONS DISEASE etc. APOPTOSIS: Role in Disease Cancer Apoptosis eliminates damaged cells (damage = mutations = cancer Tumor suppressor p53 controls senescence and apoptosis responses to damage Most cancer cells defective in apoptotic response High levels of anti-apoptotic proteins or Low levels of pro-apoptotic proteins === CANCER APOPTOSIS: Role in Disease AGING Aging -- both too much and too little apoptosis (evidence for both) Too much (accumulated oxidative damage?) --- tissue degeneration Too little (defective sensors, signals? --- dysfunctional cells accumulate hyperplasia (precancerous lesions)