2. 2
Importance of apoptosis……………………………………………3
Apoptosis : morphology of cell…………………………………….3
Classical stages of apoptosis……………………………………….3
Apoptosis vs necrosis………………………………………………4
Pathway/mechanism of apoptosis………………………………….4
Schematic representation………………………………………….5.
intrinsic pathway ………………………………………………….5
extrinsic pathway ………………………………………………….6
perforin/granzyme pathway………………………………………..7
execution pathway………………………………………………….7
Phagocytosis………………………………………………………..8
Engulfment………………………………………………………….8
References…………………………………………………………..8
Apoptosis
Apoptosis derived from Greek means "falling off". It is a process of programmed cell death
that occurs in multicellular organisms. It is a physiological way for a cell to die also called as
3. 3
physiological cell death, cell suicide or cell deletion. The Between 50 and 70 billion cells die
each day due to apoptosis in the average human adult
History: German scientist Carl Vogt was first to describe the principle of apoptosis in 1842. In
1971 the term apoptosis was coined in Greece.
Model organism used in apoptosis:
Multicellular model organisms, such as Drosophila, C. elegans, mouse and Xenopus, and
unicellular organisms, including yeast, trypanosome, and E. coli have been widely used to study
the mechanism of apoptosis. C. elegans has been proven to be an excellent model organism for
studies of programmed cell death and was used initially. Its transparency and the knowledge of
its cell lineage, including its invariant life vs. death fate of all cells, allow programmed cell death
to be studied in vivo at single cell resolution in a way that no other systems can currently match.
Genes involved in apoptosis:
Different gene families such as caspases, inhibitor of apoptosis proteins, B cell lymphoma (Bcl)-
2 family of genes, tumor necrosis factor (TNF) receptor gene superfamily, or p53 gene are
involved in the process of apoptosis. The central roles members of the ced-9 / bcl-2 and ced-
3/ICE gene families have in mediating programmed cell death in both C. elegans and humans
and the observation that these structurally similar genes are functionally interchangeable strongly
suggest that nematodes and mammals share a common molecular pathway for programmed cell
death
Characteristics:
An active and energy dependent cytological process
It is programmed or controlled by genetic protocol
It may be triggered by intrinsic or extrinsic stimuli
It occurs in almost all living creatures
Importance of apoptosis:
1) It is crucial for development. For examples the resorption of the tadpole tail. Errors in
Apoptosis can lead to Birth Defects and the formation of the fingers and toes of the fetus
4. 4
2) Important for maintaining homeostasis: Cell death is balanced with mitosis to regulate cell
number.
3) Apoptosis is needed to destroy cells that represent threat to the integrity of the organism e.g.
cells infected with viruses, cells of the immune system, cells with DNA damage or cancer cells
Apoptosis: morphology:
Biochemical events lead to characteristic cell changes (morphology) and death. These changes include;
Early: Cell shrinkage, (condensation of cytoplasm), chromatic condensation. Later: Nuclear
fragmentation, global mRNA decay, breakdown of mitochondria, cell membrane blebbing, cell
Fragmentation and apoptotic body formation and finally: Phagocytosis.
Four stages of Apoptosis:
1. Death signal (Committment to death by extracellular or intracellular triggers/signals)
2. Cell killing (execution) by activation of intracellular proteases (caspases)
C. Phagocytosis:
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Phagocytic uptake of apoptotic cells is the last component of apoptosis. Phospholipid asymmetry
and externalization of phosphatidylserine on the surface of apoptotic cells and their fragments is
the hallmark of this phase.
D. Engulfment of apoptotic cell: opsonization
The appearance of phosphotidylserine on the outer leaflet of apoptotic cells facilitates
noninflammatory phagocytic recognition, allowing for their early uptake and disposal. This
process of early and efficient uptake with no release of cellular constituents, results in essentially
no inflammatory response
References:
Elmore, S. (2007). Apoptosis: A Review of Programmed Cell Death. Toxicologic
Pathology, 35(4), 495–516. http://doi.org/10.1080/01926230701320337
Apoptosis. (2016, October 25). In Wikipedia, The Free Encyclopedia. Retrieved 15:45, October
25, 2016, from https://en.wikipedia.org/w/index.php?title=Apoptosis&oldid=746152772
Bax-induced apoptotic cell death. John Pawlowski and Andrew S. Kraft PNAS 2000 97 (2) 529-
531; doi:10.1073/pnas.97.2.529
Ooi, Hsu Kiang, and Lan Ma. “Modeling Heterogeneous Responsiveness of Intrinsic Apoptosis
Pathway.” BMC Systems Biology 7 (2013): 65. PMC. Web. 22 Nov. 2016.
Riddle DL, Blumenthal T, Meyer BJ, et al., editors. C. elegans II. 2nd edition. Cold Spring
Harbor (NY): Cold Spring Harbor Laboratory Press; 1997. Section III, Genetics of Programmed
Cell Death. Available from: https://www.ncbi.nlm.nih.gov/books/NBK20015/
Curtin, James, and Thomas Cotter. "Historical perspectives (Apoptosis)." (2003).