Kathleen Williams

Intro to Biology

Apoptosis
Apoptosis is the Greek word for falling off. It is the term commonly
used for programmed cell death. Programmed cell death is interesting
because it is actually a good thing for your body and actually helps in the
development of some parts of your body. However it has also been linked to
cancer. When cells are no longer needed, they will commit suicide by using
an intracellular death program. I found that in a healthy adult human, billions
of cells in the bone marrow and intestine will actually die about every hour! It
seems crazy that so many cells are dying especially when a majority of them
are actually healthy. Mouse paws are actually sculpted by apoptosis when
they are still developing in the embryo and when a tadpole changes into a
from cell death helps make the tail disappear.
Why is this important you may ask? Well, cells that die as a result of
an injury will swell and burst. When this happens they will actually spill their
contents onto neighboring cells which can potentially damage them. But if a
cell undergoes apoptosis it will die without the mess and its neighboring cells
are therefore safe. When a cell goes through apoptosis it will shrink and
condense. The cytoskeleton will collapse and the nuclear envelope will break
as well and the DNA will break up along with it. When the cell surface is

altered the dying cell is usually engulfed by a neighboring cell through

phagocytosis. This process also allows components of the dying cell to be
recycled by the cell that just swallowed it up.
Apoptosis is caused by caspases. What causes these morphological
changes that we recognize as apoptosis and the biochemical changes often
associated with this phenomenon? The answer is proteases. Specifically,
activation of a family of intracellular cysteine proteases which cleave their
substrates at aspartic acid residues, known as caspases for Cysteine
Aspartyl-specific Proteases. 2 These proteases are present as inactive
zymogens in essentially all animal cells, but can be triggered to assume
active states, generally involving their proteolytic processing at conserved
aspartic acid (Asp) residues. During activation, the zymogen pro-proteins are
cleaved to generate the large (20 kd) and small (10 kd) subunits of the
active enzymes, typically liberating an N-terminal prodomain from the
processed polypeptide chain. The active enzymes consist of heterotetramers
composed of two large and two small subunits, with two active sites per
molecule. 3,4 Analysis of the structures of the active sites of these enzymes,
experiments with combinatorial peptide libraries, and other data suggest
that caspases recognize the Asp residues they cleave within the context of
tetrapeptide motifs, where the most proximal (N-terminal) residue
recognized is designated P4 (position #4) and target Asp is P1 (position #1),
and where cleavage occurs at the peptidyl bond distal (C-terminal) to the
targeted Asp. This information about the structures and mechanisms of

caspases has been exploited for developing small-molecule inhibitors, which

are finding their way into clinical trials for stroke, liver failure, inflammatory
diseases, and a wide variety of other ailments.(
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1885741/) Most caspases are
directly involved with cell death at least in mammals and eukaryotes.
Activation of the intracellular cell death pathway is usually in a kind of
all or nothing fashion. The protease cascade is destructive but it is also
irreversible. So once the cell starts to destroy itself there is really no going
back.
Does cell death affect us negatively? It is healthy for the body to have
cell suicide, but what if it gets out of hand? Now a days research is proving
that the genetic basis of apoptosis implies that cell death can actually be
disrupted by mutations just like any other metabolic or developmental
program in the body. Defects in apaptotic pathways are now thought to
contribute to many diseases in the human body like cancer, stroke, heart
failure, neurodegeneration, and AIDS. Studies have shown that there is a
greater possibility that a large percentage of cell loss from tumors was
actually due to apoptosis. Thus meaning that it would majorly impact tumor
growth and/or regression. Cancer cells are actually known for their ability to
evade apoptosis. Cancer cells violate cell cycle checkpoints and can
withstand exposure to cytotoxic agents. Because of these characteristics,
they tend to survive. Apoptosis is an important barrier to developing cancer,

but if apoptosis is avoided, it becomes essential to tumor development and

resistance to cancer therapy.
I chose this topic because I thought it was interesting that our body
cells will actually destroy themselves if something is wrong with them. This is
an awesome health measure but if they are exposed to mutations can
become a health risk. Interesting how one good thing can easily become a
bad thing.

References

Reed, John C. "Mechanisms of Apoptosis." NCBI. Am J Pathol, 1 Nov.

2000. Web. 19 Nov. 2015.

Alberts B, Johnson A, Lewis J, et al.

New York: Garland Science; 2002.

Lowell, Scott W., and Athena W. Lin. "Apoptosis in Cancer."

Oxfordjournals.org. Oxfordjournals.org, 12 Oct. 1999. Web. 19 Nov.

2015.
Adapted from Cell, 144, Hanahan D, Weinberg RA, The Hallmarks of

Cancer: the next generation, 666-674, copyright 2011

Mariam, and Webster. "Apoptosis Definition." Mariam-Webster.com.
1972. Web. 19 Nov. 2015.