Naturally Programmed Cell Death, Apoptosis, and Cancer or... Folder Title: Apoptose April 12, 2005 TtlApop.

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Presentation transcript:

Naturally Programmed Cell Death, Apoptosis, and Cancer or... Folder Title: Apoptose April 12, 2005 TtlApop

What happened to your webbed feet? You guys are dethpicable. DaffyDuc

God and Michelangelo Creation by Subtraction Evolution: Selective Reproduction Selective Death Subtract

Selective Cell Death in Normal Development and Normal Organismic Functioning Developmental Remodelling Tadpole to Frog Human Fetal Remodelling Immunological Self-Tolerance Normal Physiology Post-Lactation Breast Involution Menstruation Normal Immune T-Cell Killing NormApop

Necrosis vs Apoptosis Necrosis Clumped Chromatin Swelling of Organelles Cell Distension Membrane Disruption Inflammation Apoptosis Condensed Nuclear Fragments Shrunken Cytoplasm Membrane Blebs (Apoptotic Bodies) Phagocytosis without Inflammation Kill&Die

Apoptotic Cell. Ruddon, 3rd Ed. Fig ApoCell

Membrane Blebs on a Cell Undergoing Apoptosis from Scientific American, December, 1996 ApoBlebs

DNA Lysis into "DNA Ladder". DNA from Apoptotic Cell. From Ruddon, 3rd Ed., Figure 10-8 ApoDNA

Genetic Control of "Genetically Programmed Cell Death" Cellular Location of Protein Product Mitochondrial Membrane Nuclear Envelope Endoplasmic Reticulum Nucleus Cell Membrane Effect on Apoptosis Blocks Stimulates Wild-type Stimulates Mutant Blocks Stimulates ApoGenes bcl-2 myc p53 p53* APO-1/ FAS Apoptosis Gene

Programmed Cell Death

Exogenous Genetic Suppressors of Apoptosis Adenovirus E1b Oncoprotein Ras v-abl compox crm a gene product ExoApop1

Exogenous Inducers of Apoptosis Cytotoxic T-Lymphocyte Attack on Target Cells Loss of Growth Factors Loss of Responses from Neighboring Cells DNA-Directed Anti-Neoplastic Agents ExoApop2

More Exogenous Inducers of Apoptosis (from Ruddon, 3rd Ed., p. 397) Differentiation Signals Removal of Growth Factors or Required Hormones Exposure to Transforming Growth Factor B (TGF-B) Tumor Necrosis Factor (TNF) Glucocorticoids (Immune-modulating Corticosteroids) DNA-damaging Antineoplastic Agents Environmental Toxins Agents Stimulating Ca Influx (Calcium Ionophores) Cytoskeletal-directed Microtubule Disruptors Microfilament-directed Cytochalasin B Inhibits formation of Apoptotic Bodies, but not apoptosis itself ExoApop3

TCellAct Normal T-Cell Activation by Antigen-Presenting Cells. (from Sci. Am., Dec, 1996)

TCelDown Activated T-Cell Down-regulation via FAS Cell-Surface Protein and Ligand Binding to FAS. (from Sci. Am., Dec., 1996)