Download Cell and Molecular Biology

Cell and Molecular Biology
The Apoptosis
Behrouz Mahmoudi
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Figure 17-37. Cell death. These electron micrographs show cells that have died by (A)
necrosis or (B and C) apoptosis. The cells in (A) and (B) died in a culture dish, whereas the cell
in (C) died in a developing tissue and has been engulfed by a neighboring cell. Note that the
cell in (A) seems to have exploded, whereas those in (B) and (C) have condensed but seem
relatively intact. The large vacuoles visible in the cytoplasm of the cell in (B) are a variable
feature of apoptosis. (Courtesy of Julia Burne.)
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Prenatal Development
Figure 17-35. Sculpting the digits in the developing mouse paw by apoptosis. (A) The paw in this
mouse embryo has been stained with a dye that specifically labels cells that have undergone
apoptosis. The apoptotic cells appear as bright green dots between the developing digits. (B) This
interdigital cell death eliminates the tissue between the developing digits, as seen one day later,
when few, if any, apoptotic cells can be seen. (From W. Wood et al., Development 127:5245 5252,
2000. © The Company of Biologists.)
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T-cell Development
5x10e7 T-cells/day in thymus, 2-4% escape apoptosis.
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B-cell Development
Bcl-2 translocation to
Ig promoter region
Lymphoma
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Maintenance of epithelial tissues
Figure 22-19. Renewal of the gut lining. (A) The pattern of cell turnover and the proliferation of stem cells in the epithelium that forms
the lining of the small intestine. The arrow shows the general upward direction of cell movement onto the villi, but some cells, including
a proportion of the goblet and enteroendocrine cells, stay behind and differentiate while still in the crypts. The nondividing differentiated
cells (Paneth cells) at the very bottom of the crypts also have a finite lifetime, and are continually replaced by progeny of the stem cells.
(B) Photograph of a section of part of the lining of the small intestine, showing the villi and crypts. Note how mucus-secreting goblet
cells (stained red) are interspersed among other cell types. Enteroendocrine cells are less numerous and less easy to identify without
special stains. for the structure of these cells.
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Mitochondria-independent apoptosis
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T-cell lytic granules: perforin (pores in plasma membrane)
Granzyme B (protease, Caspase-3  ICAD degradation)
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Apaf-1
Pro-caspase-9
Cytochrome C
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H
c
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Mitochondria-dependent apoptosis (Bcl-2 family proteins)
Anti-Apoptotic
Apoptotic (Multidomain)
(BH3 only)
(BH3 only activators)
(BH3 only sensitizers)
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A) MEFs from various genetic backgrounds
infected with tBid retrovirus and measured
for apoptosis after 24hours.
Annexin-V:
Phosphatidylserine
externalization.
(PS)
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bax
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ubiquitin ligase
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Cell death summary
Survival Signals
Damage or Stress
Bcl-2 proteins
Initiation
Commitment point
Execution
Mitochondrial dysfunction
Caspase cascade
Death receptors / T-cells
Morphological changes
DNA fragmentation
Nuclear condensation
PS externalization
Membrane blebbing
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