Download Cell Apoptosis

Cell Apoptosis
Puria Rafsanjani
Arvin Honari
Pardis Taheri

Apoptosis is the process of programmed cell death (PCD) that may occur in
multicellular organisms.

Biochemical events lead to characteristic cell changes (morphology) and
death.

These changes include blebbing, cell shrinkage, nuclear fragmentation,
chromatin condensation, and chromosomal DNA fragmentation.

Between 50 and 70 billion cells die each day due to apoptosis in the average
human adult. For an average child between the ages of 8 and 14,
approximately 20 billion to 30 billion cells die a day.

Excessive apoptosis causes atrophy, whereas an insufficient amount results in
uncontrolled cell proliferation, such as cancer.
Bleb & nuclear fragmentation

In cell biology, a bleb is an irregular bulge in the
plasma membrane of a cell, caused by localized
decoupling of the cytoskeleton from the plasma
membrane. Blebbing or zeiosis is the formation of
blebs.
Bleb & nuclear fragmentation
Prophase or Chromatin Condensation

Prophase is a stage of mitosis in which the chromatin
condenses into double rod-shaped structures called
chromosomes in which the chromatin becomes
visible.

This process, called chromatin condensation, is
mediated by the condensin complex.

Condensins are large protein complexes that play a
central role in chromosome assembly and segregation
in eukaryotic cells.

Unlike necrosis, apoptosis produces cell
fragments called apoptotic bodies that
phagocytic cells are able to engulf and quickly
remove before the contents of the cell can
spill out onto surrounding cells and cause
damage.
What may lead to apoptosis ?

Extracellular signals may include toxins, hormones, growth factors,
nitric oxide or cytokines, that must either cross the plasma
membrane or transduce to effect a response.

A cell initiates intracellular apoptotic signaling in response to a
stress, which may bring about cell suicide.

The binding of nuclear receptors by glucocorticoids, heat,
radiation, nutrient deprivation, viral infection, hypoxia and
increased intracellular calcium concentration, for example, by
damage to the membrane, can all trigger the release of intracellular
apoptotic signals by a damaged cell.
Glucocorticoids (GC) are a class of steroid hormones
that bind to the glucocorticoid receptor (GR), which
is present in almost every vertebrate animal cell.

A number of cellular components, such as poly ADP ribose
polymerase, may also help regulate apoptosis.
Two main methods of regulating
apoptosis


Targeting mitochondria functionality
or directly transducing the signal via adaptor proteins to the apoptotic
mechanisms.

Adaptor proteins contain a variety of protein-binding modules
that link protein-binding partners together and facilitate the
creation of larger signaling complexes.

These proteins tend to lack any intrinsic enzymatic activity
themselves but instead mediate specific protein–protein
interactions that drive the formation of protein complexes.

Another pathway for initiation identified in several toxin studies is an
increase in calcium concentration within a cell caused by drug activity, which
also can cause apoptosis via a calcium binding protease calpain.

There is also a growing body of evidence indicating that nitric oxide is able to
induce apoptosis by helping to dissipate the membrane potential of
mitochondria and therefore make it more permeable.
Cytochrome c

Cytochrome c is also released from mitochondria due to formation of a
channel and serves a regulatory function as it precedes morphological change
associated with apoptosis.

Once cytochrome c is released it binds
with Apoptotic protease activating factor
- 1 (Apaf-1) and ATP, which then bind to
pro-caspase-9 to create a protein
complex known as an apoptosome.

The apoptosome cleaves the pro-caspase to its active form of caspase9, which in turn activates the effector caspase-3.

Caspase-3 has been found to be necessary for normal brain
development as well as its typical role in apoptosis, where it is
responsible for chromatin condensation and DNA fragmentation.

MAC, also called "Mitochondrial Outer Membrane Permeabilization Pore"
is regulated by various proteins.
Bcl-2 proteins are able to promote or inhibit apoptosis by direct action
on MAC/MOMPP. Bax and/or Bak form the pore, while Bcl-2, Bcl-xL or
Mcl-1 inhibit its formation.
Execution !

Many pathways and signals lead to apoptosis, but there is only one
mechanism that actually causes the death of a cell.

After a cell receives stimulus, it undergoes organized degradation of
cellular organelles by activated proteolytic caspases.

Proteolysis is the breakdown of proteins into
smaller polypeptides or amino acids. This
generally occurs by the hydrolysis of the peptide
bond, and is most commonly achieved by cellular
enzymes called proteases.
characteristic morphology of a cell
undergoing apoptosis

Cell shrinkage and rounding are shown because of the breakdown of the
proteinaceous cytoskeleton by caspases.

The cytoplasm appears dense, and the organelles appear tightly packed.

Chromatin undergoes condensation into compact patches against the
nuclear envelope in a process known as pyknosis, a hallmark of
apoptosis.

The nuclear envelope becomes discontinuous and the DNA inside it is
fragmented in a process referred to as karyorrhexis. The nucleus breaks
into several discrete chromatin bodies or nucleosomal units due to the
degradation of DNA.

The cell membrane shows irregular buds known as blebs.

The cell breaks apart into several vesicles called apoptotic bodies, which
are then phagocytosed.