1. Apoptosis
By Erika Amberson
Cell Suicide:

2. Overview of research into apoptosis
• 1800sObservation of cell death
• 1908 Mechnikovwins Nobel prize for
phagocytosis
• 1930-40 Studies of metamorphosis
• 1948-49Cell death in chick limb
• 1955 Beginning of studies of lysomes
• 1964-66 Necrosis & PCD described
• 1971 Apoptosis term established
• 1977 Cell death genes in C.
elegansdiscovered
• 1980-82 Caspase-3 (ced-3) identified
• 1989-91 Apoptosis genes identified,
ced-3 sequenced
(Richerdet.al., 2001)

3. What is Apoptosis?
• Programed cell death
• Orderly demise of cell
• Essential for multi-cellular
organisms survival during cell
division
• Important for cellular
development

4. Ex: Finger webbing in humans
• Body produce millions
more cells than needed
• Cells that do not form
synaptic connections
undergo apoptosis
• Some cases cells do not
undergo cell death,
webbing remains

5. Necrosis vs. Apoptosis
Cell death by injury
• Cells swell
• Membrane rupture
• Cell lyses occurs
• Inflammation
• Mechanism- APT depletion,
membrane injury, free radical
damage
• Areas of tissues are affected
Cell death by suicide
• Cell shrinkage
• Membrane remain intact
• Cell is phagocytosed
• No inflammation
• Mechanism – capases
activated, endonuclease and
proteases
• Individual cell affected

6. Necrosis Vs. Apoptosis
Wilde, 1999

7. Stages of Apoptosis
1. Cell damaged, stressed, or trigged by body signal
2. Mitochondrial leakage
3. Cell shrinkage
a) Chromatin condensation
b) Nuclear fragmentation
4. Enzymatic breakdown (membrane blebbing)
5. Nucleus destroyed
6. Phagocytosis occurs

9. Caspase:
Cysteine-aspartic proteases
• Essential role in apoptosis,
necrosis and inflammation
• Required for immune system in
maturation of lymphocytes
• Aids in cell differentiation &
proliferation

10. Pathways
Extrinsic Pathway
• Death receptor
• Initiated from outside the cell
• Activated through pro-apoptotic
receptors (ligands) on cell
surface
Intrinsic Pathway
• Mitochondrial
• Initiated from within the cell
• Activated in response to signals
from DNA damage (cell stress)

11. • Binding of Fas by Fas ligand induces recruitment
of Fas protein
• Inside of cell Fas protein recruits adaptor
protein that bind procaspase 8
• Caspase-8 is activated
• Caspase-8 activates Caspase-3
• Caspase -3 cleaves other proteins
• Signal cascade occurs releasing Cytochrome- c
from the mitochondria activating ApaF-1
• ApaF-1 binds with Caspase-9 creating an
Apoptosome
• Apoptsome activates Caspase-3 which cleaves
the actin cytoskeleton and apoptosis occurs

12. • Absence of Tropic Factor from
trophic factor receptor
• p53 protein phosphorylated
• Inhibiting Bcl-2 &Bcl-XL releasing
pro-apoptotic regulator Bax
• Cytochrome c is released and binds
ApaF-1
• ApaF-1 binds with procaspase-9
activating the caspase cascade
• ApaF-1 binds with Caspase-9 creating
an Apoptosome
• Apoptsomeactivates Caspase- 3 which
cleaves the actin cytoskeleton and
apoptosis occurs

13. Diseases associated with Apoptosis
Inhibits Apoptosis
• Cancer
• HPV
• Melanoma
• Autoimmune Disorders
• Systemic Lupus
• Immune-mediate glomerulonephritis
• Viral Infections
• Herpes
Increases Apoptosis
• AIDS
• Neurodegenerative Disorders
• Alzheimer’s Disease
• Parkinson’s Disease
• Ischemic Injury
• Stroke
• Myocardial infarction
• Toxin-Induced liver disease
• Alcohol

14. Future research…….
• How cells are selected in vivo for cell death
• How effector caspases are able to trigger
apoptosis specifically for targeted cells and
not elicit a full blow apoptotic response
• Further understanding of cell death
regulations to help treat a variety of human
disorders that are specific to programmed
cell death