Apoptosis+BO.pdf

Apoptosis ...from beginning to end Dr. Birgit F. Osterhoff Apoptosis from beginning to end Greek: apo – from, ptosis – falling, translates to the dropping off of petals or leaves from plants or trees Apoptois is the process of Programmed Cell Death (PCD) Multi-biochemical, hightly controlled event In contrast; Necrosis is uncontrolled cell death from acute cellular injury Ongoing increase in Apoptosis research since the early ’90 Many focus areas such as uncontrolled proliferation = Cancer As an example, Apoptosis is needed in the differentiation of fingers during development of the embryo ~50 to 70 billion of cells undergo apoptosis every day (average human adult) In one year the mass of the cells undergoing apoptosis is ~equal to the weight of the individual body Apoptosis versus Necrosis Induction and Regulation of Apoptosis Induction DNA damage (ionizing radiation ) Infection (e.g. virus) Cell stress (e.g. starvation) Homodynamics (homeostasis) Control: Cell signals Hormones Growth factors Cytokines Nitric oxide Regulation cell-cell interaction 6 Normal Cell Apoptotic Body (AB) Formation Lysis of AB Continued Blebbing Cell shrinkage Chromatin Condensation Membrane Blebbing Nuclear Collapse The Apoptosis Process Induction of Apoptosis 7 Apoptosis Induced Cell Function Changes Normal Cell Lysis of AB Metabolic activity Mitochondrial transition pore opening Phosphatidyl serine (PS) translocation Caspase activity DNA condensation Plasma membrane integrity DNA fragmentation - - - + + + + + Mitochondrial membrane potential Induction of Apoptosis ? An intrinsic part of evaluating any biological system is the ability to mimic or inhibit relevant pathways. ? Systematic analysis of biologic systems begins with the initiation of cell signaling, typically via receptor-ligand interactions Apoptosis was induced in mouse L929 cells using recombinant TNF. Cytotoxic activity was measure