Apoptosis and Diseases The Nobel Prize in Physiology or Medicine 2002 for their discoveries concerning 'genetic regulation of organ development and programmed cell death 囻厦 Sydney brenner H. Robert Horvitz John E Sulston 0 1/3 of the prize 1/3 of the prize 1/3 of the prize United Kingdon USA United Kingdom The Molecular Massachusetts The Wellcome Trust Sciences InstituteInstitute of Sanger Institute Berkeley, CA, USA Technology(MIT) Cambridge, United Cambridge, MA, Kingd。m USA
Apoptosis and Diseases
1. Concept 2. Apoptotic process and changes 3. Key molecules and Major pathways 4. Techniques to detect apoptosis 5. Apoptosis-related diseases Insufficient apoptosis in diseases Excessive apoptosis in diseases Coexistence of insufficient and excessive apoptosis in diseases 6. Principles of treatment
1. Concept 2. Apoptotic process and changes 3. Key molecules and Major pathways 4. Techniques to detect apoptosis 5. Apoptosis-related diseases • Insufficient apoptosis in diseases • Excessive apoptosis in diseases • Coexistence of insufficient and excessive apoptosis in diseases 6. Principles of treatment
What is Apoptosis t apoptosis refers to the process in which the dying procedures_that have been in advance deposited in cell are triggered by various causes from in vitro and in vivo, and eventually cause cell death + Programmed cell death (PCD) Final stage of apoptosis White blood cell 器·额 a CSgO
What is Apoptosis ? Apoptosis refers to the process in which the dying procedures that have been in advance deposited in cell are triggered by various causes from in vitro and in vivo, and eventually cause cell death. Programmed cell death（PCD）
Causes and Process of Apoptosis Inhibitory Factors Stimulatory Factors Physiological Initiation Physiological GFS, estrogen, etc, Fasl. Pathological Pathological virus: chemicals, etc glutamate, free radicals; therapeutics Regulation Conserved Execution growth factor Glucocorticoids activat radiation essential ceptor attacks target Phagocytosis Unknown Unknown Requires po3 trigger Initiated by death
Initiation Regulation Execution Phagocytosis Physiological: GFs, estrogen, etc; Pathological: virus; chemicals, etc. Inhibitory Factors Stimulatory Factors Physiological: FasL; Pathological: glutamate, free radicals; therapeutics. Conserved Causes and Process of Apoptosis
Apoptotic changes Morphological changes in apoptosis ---Biochemical Changes in Apoptosis
Apoptotic changes ---Morphological changes in apoptosis ---Biochemical Changes in Apoptosis
Morphological changes in apoptosis 豢 Cell membrane coplasm 豢 Cell nucleus + Apoptotic body Phagocytose Normal Cell condensation margination Budding poptotic Cel poptotic bodies Changes of cell membrane
Morphological changes in apoptosis Cell membrane Cytoplasm Cell nucleus Apoptotic body Phagocytose Normal Cell Apoptotic Cell condensation margination Apoptotic Bodies Budding Changes of Cell membrane
Apoptosis and Necrosis Apoptosis Necrosis Nature Physiologicalor Pathological accidental pathological; specific Stimulus Mild Strong Biochemistry Active, energy-dependent, Passive, energy-independent,no new protein synthesis protein synthesis DNA Specific degradation. Random degradation ladder(180-200 bp) Morphology Intact, shrinkage, Lysis, swelling condensation Inflammation No Y Apoptotic body Y No Gene regulation Yes No
Apoptosis Necrosis Nature Physiological or pathological; specific Pathological, accidental Stimulus Mild Strong Biochemistry Active, energy-dependent, new protein synthesis Passive, energy-independent, no protein synthesis DNA Specific degradation, ladder (180-200 bp) Random degradation Morphology Intact, shrinkage, condensation Lysis, swelling Inflammation No Yes Apoptotic body Yes No Gene regulation Yes No Apoptosis and Necrosis
Morphological differences in apoptosis and necrosis NECROSIS APOPTOSIS Mild convolution Chromatin clumping Swollen organelles Chromatin compaction Flocculent mitochondria and segregation Condensation of Nuclear fragmentation Blebbing Apoptotic bodies Disintegration Release of Apoptotic body intracellular contents Phagocytic ll Inflammation
Morphological differences in apoptosis and necrosis
Biochemical Changes in Apoptosis 秦 Caspase activation Endonuclease activation
Biochemical Changes in Apoptosis Caspase activation Endonuclease activation
Caspases: (cysteine-containing aspartate-specific proteases) Most apoptotic proteolytic cleavage results from the action of caspases Caspases are activated by proteolytic cleavage > Removal of prodomain and linker region Assembly of the large and small subunits into an active enzyme complex >Two heterodimers interacting via the small subunits to form a tetramer with two catalytic sites Family members>14
➢Most apoptotic proteolytic cleavage results from the action of caspases ➢Caspases are activated by proteolytic cleavage ➢Removal of prodomain and linker region ➢Assembly of the large and small subunits into an active enzyme complex ➢Two heterodimers interacting via the small subunits to form a tetramer with two catalytic sites ➢ Family members>14 Caspases: (cysteine-containing aspartate-specific proteases)