Cell Death-Apoptosis

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Cell Death-Apoptosis

• Lecture 39B BSCI 420,421,620 Dec 4,
  2002
• Its not that Im afraid to die, I just dont
  want to be there
• when it happens - Woody Allen
• Cell and Tissue Renewal in Animals
• Cell death - Apoptosis

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2. Cell death - Apoptosis Cell biologists have
come to realize that most cell death is not
accidental (Necrosis- cell death due to
injury) but is programmed cell death. Cells are
killed by a regulated series of biochemical
events, whereby one cell commits suicide for the
good of the organism. This kind of cell death is
called Apoptosis. (B C below) (Gr. Loss of
parts like leaves from a tree)
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What do I mean by dying for the good of the
whole organism? This is how our fingers emerge
from a club-like paw (mouse paw Stained with a
dye that labels cells in apotosis B one day
later)
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Specific genes for Apoptosis were discovered in
the nematode C. elegans. These cell death genes,
when mutant, have the phenotype of failure of
certain specific cells (131) to die when they
should during development. Similar genes later
discovered in vertebrates Regulator Adapter Eff
ector Worm Ced 9 Ced 4 -gt Ced 3
-gtDeath Vert. Bcl-2 Apaf-1 -gt Casp 9
-gtCasp3-gtDeath Caspases are cysteine
aspartases, proteases that split proteins
at aspartate residues to
break down cell structures
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Fas is a cell-death receptor activated by Fas
ligand on another cell such as a killer T-cell.
Eg to kill a virus infected or tumor cell.
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When DNA is damaged, eg by radiation, cells use
p53 pathways to either halt cells in cycle, or to
signal cell death. How is that choice made? When
damage is repairable, med amounts of p53 are
activated.
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• When damage is irreparable, p53 is activated at
  high levels and
• activates the transcription of several cell death
  genes, including
• Bax stimulates release of cyt C from
  mitochondria
• Fas cell death receptor
• Apaf-1 Apoptotic protease activating factor

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These activate the mitochondrial cell death
pathway (Model) Bax Bid interact w VDAC (mit
porin) to cause formation of a large channel that
releases cytochrome C procaspase 9 from the
intermembrane space of mitochondria. Cyt C binds
to Apaf-1 activating it so it can bind procaspase
9 form a scaffold. On this scaffold, procaspase
9 mols split each other to initiate the caspase
cascade and cell death. Caspase
9 Procaspase 9
Cell Death
Apaf-1 cyt C VDAC Bax Bid
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Suppression of Apoptosis by survival (trophic)
factors
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Suppression of Apoptosis by survival (trophic)
factors Bcl-2 inhibits Bax from
forming cyt C release channel Thus Bcl-2 is a
major anti-apotosis factor.