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INTRODUCTION
Programmed cell death that occur in
multicellular organisms
Apoptosis plays major role in
embryogenesis to senescence
Apoptosis differ from necrosis
Necrosis Apoptosis
Cellular swelling Cellular condensation
lysis of cell after infection Programmed cell death
No cell signallinig is there Undergo apoptosis only after
undergo cell lysis by other recieving cell signal
factors Blebbing occurs
No blebbing occurs Membranes remain intact
Membranes are broken Organelles are condensed
Membranes are expanded and loss of function
and thus loss of function Requires ATP
ATP is depleted Cell is phagocytosed, no
Necrotic cells are bursted to tissue reaction
cell envt No inflammatory responses
inflammatory reaction Ladder-like DNA
DNA fragmentation is fragmentation
random, or smeared In vivo, individual cells
In vivo, whole areas of the appear affected
tissue are affected No immune response
Immune response
NECROSIS Vs
APOPTOSIS
Wilde, 1999
Death by Injury vs. Death by Suicide
(Necrosis vs. Apoptosis)
What makes a cell commit suicide?
withdrawal of positive signals (growth factors, Il-2)
Steps in apoptosis:
the decision to activate the pathway;
"suicide" of the cell;
engulfment of the cell remains by specialized immune cells called
phagocytes;
degradation of engulfed cell.
The changes in cell death :
condensing of the cell nucleus and breaking it
into pieces
condensing and fragmenting of cytoplasm into
membrane bound apoptotic bodies;
breaking chromosomes into fragments
containing multiple number of nucleosomes (a
nucleosome ladder)
Apoptosis Triggered via Two Pathways
Intrinsic or mitochondrial pathway
Extrinsic or death receptor pathway
STAGES OF APOPTOSIS
Healthy cell
EXECUTION (irreversible)
DEGRADATION
STAGES OF APOPTOSIS
Effector
Intrinsic Pathway
Caspase 3 PCD
DNA Initiator
Mitochondria/
damage Caspase 9
Cytochrome C
& p53
Extrinsic or Binding of Fas by FasL
Death Receptor induces recruitment of
Pathway FADD to the cytoplasmic
tail of Fas
The opposite end of FADD
contains a death effector
domain (hatched boxes);
recruitment of either
procaspase-8 or c-FLIP
Caspase-8 can cleave Bid
truncated Bid (tBid) can
inactivate Bcl-2 in the
mitochondrial membrane.
This allows the escape of
cytochrome c, which
clusters with Apaf-1 and
caspase-9 in the presence
of dATP to activate
caspase-9.
Smac/DIABLO is also
released from the
mitochondria and
inactivates inhibitors of
apoptosis (IAPs).
breakdown of several
cytoskeletal proteins and
degradation of the inhibitor
of caspase-activated
SIGNIFICANCE OF APOPTOSIS
Important in normal physiology
Development: Immune systems
maturation, Morphogenesis
Adult: DNA Damage and wound repair.
Excess apoptosis
Neurodegenerative diseases
Deficient apoptosis
Cancer
Autoimmunity
CANCER
Apoptosis eliminates damaged cells(damage => mutations
=> cancer
replacement is inefficient)
Neuronal death caused by loss of proper connections, loss of proper growth factors
PARKINSON'S DISEASE
ALZHEIMER'S DISEASE
HUNTINGTON'S DISEASE etc.