APOPTOSIS : THE

PROGRAMMED CELL DEATH

Materi ajar disusun oleh: Fenryco Pratama

apoptosis

• Discover and rediscovery along 2 century

• Final name, apoptosis: Currie and collegue 1972

• Different morphological

Apoptosis vs necrosis

What is apoptosis?

Necrosis?

Feature of apoptotic cell

• Shrinkage in volume of the cell and its nucleus

• Loss of adhesion to neighboring cells

• Formation of blebs at the cell surface

• Chromatin fragmentation

• Engulfment by phagocytotic cell

Modified from [Van Cruchten, 2002]. http://www.celldeath.de/encyclo/aporev/revfigs/revfig_2.htm

http://www.cyto.purdue.edu/flowcyt/research/cytotech/apopto/data/chap10.htm

http://www.cyto.purdue.edu/flowcyt/research/cytotech/apopto/data/malorni/malorni.htm

apoptosis

• Important in maintaining homeostatis in multicellular organism

• Failure to regulate apoptosis can result serious damage to the organism

Faktor yang mempengaruhi apoptosis

• Stimulus internal

• Stimulus eksternal

Apoptosis: a biochemistry view

• Caspase, the central executioner

• Degrade the protein and activate other protein

• Nuclease

• Degradation of cytoskeleton: lamina nukleus, fodrin, gelsolin

• Activate p21: bebling effect

Caspase activation

• Processing by an upstream caspase

• Induced proximity

• Association with a regulatory sub unit

Caspase targeting

• Protein kinase; FAK, PKB, PKC dan Raf1

• Lamins

• Protein of cytoskeleton; intermediate filament, actin, tubulin, gesolin

• Endonuclease: caspase activated DNase

Apoptosis as a protein-protein interaction

• Caspase prodomain have a protein-protein interaction module

• Bcl-2: control of cell death. Direct binding to CED-4, facilitate cythocrome c release from mt

Bcl-2 family members

• Intrinsic pathway apoptosis

• Pro-apoptotic: Bad, Bax

• Antiapoptotic: Bcl-xL, Bcl-W, and Bcl-2

Bcl-2 family members and Caspase activation

• Bcl-2 members form channel to facilitate protein transport

• Bcl-2 members interact with other protein to form a channel

• Bcl-2 members induce rupture of the outer mitochondrial membrane

Apoptosis as a protein-protein interaction

• IAP

• Smac/DIABLO

Is caspase activation the defining feature of apoptotic cell death?

• Most if not all

• Activation apoptotic program without caspase

Daftar Pustaka dan Rujukan

1. Gerald Karp. “Cell And Molecular Biology: Concept and Experiments 6th edition.” Wiley

2. Michael O Hengartner. “ The Biochemistry of Apoptosis”. Nature Insight Review Article

3. http://www.nature.com/nature/insights/6805.html

Daftar Pustaka dan Rujukan

• Website (tanggal akses 23 Maret-26 Maret 2011)

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