Lecture notes
First Class Lecture notes Cancer Biology (DNA and Disease)
- Module
- Cancer Biology
- Institution
- University Of Bath (UoB)
Apoptosis lecture notes
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ApoptosisEvading apoptosis is a hallmark of cancer.
Types of cell death
APOPTOSIS – cell death as a result of
activation of an intracellular ‘suicide’
programme. It is a normal and essential
event during development generally and
within the immune system. Apoptosis does
not lead to lysis of cells and thus avoids
damage to neighbouring tissue.
NECROSIS - death of cells or tissues as a result of external trauma such as
physical damage or lack of oxygen. It results in cell lysis and damage to
surrounding tissues.
AUTOPHAGY – self-digestion, sometimes seen in cells, apparently mediated by
lysosomes. Autophagy by itself is
not a death response (is actually a
survival response), but depending
on the type of stress, cell could
enter necrosis or apoptosis.
Differences between necrosis
and apoptosis:
Necrosis: Typically in
necrosis, the cell swells
up (accumulation of
water), but number of
organelles doesn’t
change. There are
chromosomal changes
and swelling of mitochondria. The plasma membrane then breaks
down and the cell bursts open, spilling its contents into
environment. Triggers inflammatory response – immune cells
attracted to site.
Apoptosis – cell size remains the same but shape changes.
Budding off of a single cell into different compartments, but all the
cellular components are contained (cell does not burst). Apoptotic
bodies are engulfed/ phagocytosed by another cell (could be a
neighbouring cell or immune cell). Fragmentation of the nucleus is a
key hallmark, as well as blebbing: when a cell detaches its
cytoskeleton from the membrane, causing the membrane to swell
into spherical bubbles, greatly distorting the shape of the cell.
, 3 key events:
a) Release of cytochrome
c from mitochondria into
the cytosol.
b) Asymmetry of lipid
layers that forms plasma
membrane breaks down –
phosphatidylserine
(phospholipid component
of the plasma membrane)
becomes exposed on
outside of cell instead of
Basic apoptotic
machinery:
DNA fragmentation
Chromatin
condensation
Membrane blebbing
Cell shrinkage & disassembly into apoptotic bodies
Engulfment
Significance of apoptosis:
Normal development.
e.g. Oocyte development: the body generates excess numbers of oocytes which
are killed off via apoptosis. In the mammalian female ovaries, apoptosis claims
more than 99.9% of the potential germ cells. Although most germ-cell deaths
take place before birth, apoptosis continues to decimate the number of oocytes
during juvenile and adult life. Once the supply of oocytes has been exhausted
through ovulation and apoptosis, the ovaries senesce, leading to infertility and,
in humans, to the menopause.
Immune system activation:
E.g. CD8 cells that apoptose infected target cells: Autoimmune disease is caused
by the deregulation of normal apoptosis in the immune system.
Disease states:
Too little apoptosis = cancer (uncontrolled cell proliferation)
Too much apoptosis = AD (destruction of neurones via apoptosis)
What triggers apoptosis?
1. Growth factor withdrawal – cells require a serum which is rich in growth
factors. When these growth factors are removed, this will trigger apoptosis
(this is a negative trigger)
2. Specific ‘death’’ ligands – activation of ligands (positive trigger)
3. Loss of contact with surroundings – a detached cell that has lost
contact with required substrate will undergo apoptosis
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