By: Thinh Le

Introduction

• The word apoptosis was introduced by Kerr, Wyllie and Currie to describe a form of cell death distinct from necrosis.

• Apo = [Greek] : from, separation from; Ptosis= [Greek] : dropping, a falling down

Apoptosis vs NecrosisApoptosis vs Necrosis

Apoptosis Apoptosis

• Chromatin condensation• Cell Shrinkage• Preservation of Organellesand cell membranes• Rapid engulfment byneighboring cellspreventing inflammation

Necrosis

• Nuclear swelling• Cell Swelling• Disruption of Organelles• Rupture of cell and releaseof cellular contents• Inflammatory response

1972 Kerr Wyllie Currie

Evolution of the Origin of Evolution of the Origin of Programmed Cell Death (PCD)Programmed Cell Death (PCD)

• Mitochondria retain their collection of molecule that can trigger cell suicide after the enter the stabilize in the eukaryotic cell.

• This process has evolved to occur only when programmed.

Purpose of Apoptosis

• It’s essential for the proper development and to maintain homeostasis for the organism.

Inititation

• DNA damage within the cell.• Cancerous cells• Cells of the immune system after they have

fulfilled their function• Ionizing Radiation• Stress and infection such as virus

Types of Induction:Cell surface death receptor mediated pathway (extrinsic)Mitochondrial-initiated pathway (intrinsic)

Caspases

•Family of Proteins- main executors of the apoptotic process.

•They belong to a group of enzymes known as cysteine proteases.

•Zymogens- inactive forms

•Caspase 8 and 10- initiator (extrinsic)•Caspase 9- initiator (intrinsic)

•Lead to effector caspase 3 and 6•Cleave key cellular proteins

Other Important Proteins

• Blc-2 family helps regulate the activation of procaspases.• Inhibitors - Bcl-2, Bcl-XL

• Promoters – Bad, Bax, Bak

Mechanism (Extrinsic)• Death Receptors- cell surface receptor that transmit

apoptotic signals, initiated by ligands.• Ligands: Fas ligand, Tumor Necrosis Factor (TNF)

alpha, and Tumor necrosis (TNF)-related apoptosis-inducing ligand TRAIL.

• Lead to generation of ceramide• Result in large number of clustering of death

receptors.• This helps strengthen the apoptotic signaling.

• Death domain• Conformation change in the intracellular domain of

the receptor. • Allows recruitment of various apoptotic proteins to the

receptor.

Death Inducing Signaling Complex

Mechanism (Extrinsic) cont.

• Final step- recruitment of caspase 8• Resulting the activation of caspase 8

and the initiation of apoptosis.

Mechanism (Extrinsic) cont.

Mechanism (Intrinsic)

• Mitochondria contains proteins like Apoptosis Inducing Factor (AIF), Smac/ DIABLO and Cytochrome C that regulate cell death.

• These proteins are release through the a pore called Permeability Transition (PT) pore• Form by pro-apoptotic members of Bcl-2

family (activated by apoptotic signals)• The release of Cytochrome leads to recruitment

of pro-caspase 9 and Apoptotic protease

activating factor 1 (Apaf-1).• This forms the apoptosome

Mechanism (Intrinsic) cont.

• This is follow by the activation of caspase 9 which in turn result with the induction of apoptosis.

Mechanism (Intrinsic) cont.

Review

Conclusion

References • Albanese, Joseph, Nicholas D. Ionizing Radiation Alters Fas Antigen Ligand

at the Cell Surface and on Exfoliated Plasma Membrane-Derived Vesicle: Implications for Apoptosis and Intercellular Signaling. Yale University

School of Medicine. Radiation Research pg. 49-61 (2000)

• Alberts, Bruce, Alexander J., Julian L., Martin R., Keith R., Peter W. Molecular Biology of The Cell 4th Edition. Garland Science. pg. 1010-1014.

Chiarugi and Moskowitz. PARP-1--a perpetrator of apoptotic cell death? Science 297, p. 2008

• Almasan, Alex. Cellular Commitment to Radiation-Induction Apoptosis. Department of Cancer Biology. pg. 347-350 Vol. 153 Issue 3 (March 2000)

• Bruchhaus, Iris. Protozoan parasites: Programmed Cell Death as a Mechanism of parasitism. Bernhard Nocht Inst. Trop. Medicine. Trends in Parasitology

23, no. 8 (August 2007):376-383

• Ejima, Kuniaki. Inductionn of Apoptosis in Placentas of Pregnant Mice Exposed to Lipopolysaccharides: Possible Involvement of Fas/Fas Ligand System. University of Occupational and Environmental Health. Biology of Reproduction 62, 178-185 . 17 May 1999.

• Park, HeonJoo. Apoptosis and Cell Cycle Progression in an Acidic Environment After Irradiation. University of Minnesota Medical School. Radiation Research pg. 295-304 vol. 153:3 (March 2000)