病理学课件7.ppt

Apoptosis and Diseases;Concept Major pathways Key molecules Apoptosis-related diseases Insufficient apoptosis in diseases Excessive apoptosis in diseases Coexistence of insufficient and excessive apoptosis in diseases Principles of treatment;History of Cell Death Research;;Using C. elegan as a model;;Conserved apoptotic paradigms in C. elegans, Drosophia, and mammals;Death receptor-mediated apoptotic pathway Mitochondria-mediated apoptotic pathway Nuclear-mediated apoptotic pathway;;death-inducing signaling complex;Mitochondrial Membrane Permeabilization (MMP) in Apoptotic Process;ER and Apoptosis;Cross-talking among Organelles and Molecules in Apoptosis ;;1. Activation of endonuclease 2. Activation of caspases ; Role of Endonuclease;Role of Caspases;Phosphatidylserine (PS) receptor (PSR) acts as a ‘tickle’ receptor for uptake of apoptotic cells;;Table 1. Caspase-deficient miceKnockout Phenotype Caspase-1 Viable; impaired processing of IL-1; resistant to endotoxic shock. Caspase-2 Viable; excess numbers of female germ cells; oocytes resistant to chemotherapeutic drugs; B lymphoblasts resistant to granzyme B; accelerated death of facial neurons during development and of sympathetic neurons deprived of NGF. Caspase-3 Lethality at 3–5 weeks of age; defective neuronal apoptosis; T cells resistant to antigen-induced death; abnormal apoptotic morphology in dying cells. Caspase-8 Lethality around E12.5; hyperemia and abnormal heart muscle development; MEFs resistant to TNF, Fas and DR3 but sensitive to UV irradiation, etoposide, staurosporine, serum deprivation. Caspase-9 Perinatal lethal; impaired neuronal apoptosis; ES cells, MEFs and thymocytes generally resistant to intrinsic death stimuli such as DNA damage, though resistance depends on