chapter 18 apoptosis apoptosis is only one form of programmed cell death. in animal cells, cell...

Click here to load reader

Post on 23-Dec-2015

226 views

Category:

Documents

6 download

Embed Size (px)

TRANSCRIPT

  • Slide 1
  • Chapter 18 Apoptosis Apoptosis is only one form of programmed cell death. In animal cells, cell necrosis is another form of programmed cell death.
  • Slide 2
  • Two distinct forms of cell death apoptosis and necrosis Programmed cell death eliminates unwanted cells
  • Slide 3
  • In metazoans, apoptosis is vital for - normal development - maintenance of tissue homeostasis - an effective immune system Its disturbance is implicated in numerous pathological conditions ranging from degenerative disorders to autoimmunity to cancer Sculpting the digits in the developing mouse paw by apoptosis
  • Slide 4
  • Apoptosis during the metamorphosis of a tadpole into a frog
  • Slide 5
  • Apoptotic cells are biochemically recognizable Characteristic biochemical changes in cells undergoing apoptosis 1.Chromosomal DNA cleaved into fragments 2.Change in the plasma membrane phosphatidylserine in the outer leaflet 3.Loss of electrical potential across the inner membrane of the mitochondria 4.Relocation of cytochrome c from the intermembrane space of the mitochondria to the cytosol
  • Slide 6
  • Cleavage of chromosomal DNA into a characteristic ladder of fragments
  • Slide 7
  • Apoptosis depends on an intracellular proteolytic cascade that is mediated by caspases Procaspase activation during apoptosis
  • Slide 8
  • Some human caspases Caspases involved in inflammationcaspases 1 (ICE), 4, 5 Caspases involved in apoptosis Initiator caspasescaspases 2, 8, 9, 10 Executioner caspasescaspases 3, 6, 7 Examples of target proteins Nuclear lamins Protein that holds the endonuclease in an inactive state Components of the cytoskeleton and cell-cell adhesion proteins
  • Slide 9
  • Slide 10
  • The two best understood signaling pathways that activate a caspase cascade in mammalian cells are the extrinsic pathway and the intrinsic pathway Each pathway uses its own initiator procaspases and activation complex
  • Slide 11
  • Cell-surface death receptors activate the extrinsic pathway of apoptosis The extrinsic pathway of apoptosis activated through Fas death receptors
  • Slide 12
  • The intrinsic pathway of apoptosis depends on mitochondria
  • Slide 13
  • Release of cytochrome c from mitochondria during apoptosis
  • Slide 14
  • Bcl2 proteins regulate the intrinsic pathway of apoptosis The three classes of Bcl2 proteins
  • Slide 15
  • The three major mammalian factions of the Bcl-2 family. The BH3-only proteins (yellow) are essential initiators of apoptosis that primarily antagonize their pro- survival relatives (blue), whereas either Bax or Bak (red) is required downstream of Bcl-2.
  • Slide 16
  • The role of BH123 pro-apoptotic Bcl2 proteins (mainly Bax and Bak) in the release of mitochondrial intermembrane proteins in the intrinsic pathway of apoptosis
  • Slide 17
  • How pro-apoptotic BH3-only and anti-apoptotic Bcl2 proteins regulate the intrinsic pathway of apoptosis
  • Slide 18
  • IAPs inhibit caspases A proposed model for the roles of IAPs and anti-IAPs in the control of apoptosis in mammalian cells
  • Slide 19
  • Extracellular survival factors inhibit apoptosis in various ways
  • Slide 20
  • Three ways that extracellular survival factors can inhibit apoptosis
  • Slide 21
  • Either excessive or insufficient apoptosis can contribute to disease
  • Slide 22
  • Slide 23
  • Slide 24
  • Slide 25
  • Slide 26
  • Slide 27
  • Slide 28