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Apoptosis and it's bioenergetics

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Mustafa Mehkary

on 30 April 2014

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Transcript of Apoptosis and it's bioenergetics

Death by Injury (
Necrosis
)
Mechanisms of cell death
Apoptosis and its Bioenergetics
• Apoptosis is equally significant in both plants and animals.
• Possibility of exploitation by artificially adding factors that may trigger Apoptosis.
• For now, this possibility is far from reality. Although insights into the biochemistry and energetics of Apoptotic pathway have led us to make a hypothetical plot of Apoptosis, but the information presented up till now is more like the scattered pieces of a jigsaw puzzle, that we need to put together.

What happens when we do manage to get to exploit different steps of Apoptotic Pathway?

Apoptosis-directed therapeutic agents are expected to selectively influence the apoptotic process in disorders where
insufficient apoptosis

occurs.

Diseases where
excessive apoptosis
occurs and needs to be attenuated.

We can use apoptosis to treat many diseases and all this could be done by knowing about the basic chemistry of the pathway.

Conclusion
Apoptosis occurs under normal physiological conditions while necrosis is often a response to a viral infection or other factors.
Apoptosis vs Necrosis
APOPTOSIS
Apoptosis involves many biological and cellular processes that involve changes in biochemistry. Thus, bioenergetics and biochemistry of apoptosis is very important to regulate, so that we can manipulate these processes for future use.
Apoptosis or programmed cell death is required for
Proper
development
removal of cells or organisms that are
harmful
to the cell.
Significance of Apoptosis
Mechanism
Death by Suicide (
Apoptosis
)
It occurs due to
tissue damage
and by some
toxic substances
.
In this case, cells undergo a series of
chemical changes
like swelling, inflammation and cell content leakage.
Basically,
Necrosis

begins when a cell is impaired in its homeostatic ability
, water and extracellular ions move into the cell, the organelles and cell swell and burst due to ultimate breakdown of the plasma membrane
In
Apoptosis
cells undergo programmed death.
The death of a cell is determined genetically or by some other factors
Apoptosis refers to programmed cell death, it is the intentional killing or disposing-off of the cells and is beneficial.
Cells that undergo apoptosis share common morphological changes. Generally, they shrink and develop bubble-like
blebs
on their surface.
The chromatin (DNA and protein) in their nucleus is degraded and their mitochondria breakdown with the release of cytochrome c.
As a tadpole changes into a frog, the cells in the tadpole tail are induced to undergo apoptosis; as a consequence, the tail is lost
Ever wondered why humans or most
mammals don't have webbed feet and hands?
The paw in this mouse embryo has been stained with a dye that specifically labels cells that have undergone apoptosis. The apoptotic cells appear as
bright green
dots between the developing digits. This interdigital cell death eliminates the tissue between the developing digits, as seen one day later. In mice and other developing embryo's the tissue connection between the fingers is removed by apoptosis.
The formation of the proper connections (synapses) between neurons in the brain requires that surplus cells be eliminated by apoptosis.
The elimination of T cells that might otherwise mount an autoimmune attack on the body occurs by apoptosis.
Cell that contain damaged or mutated DNA are required to be immediately removed so that they do not produce such proteins that prove to be harmful for the cell. Thus death of these cells is regulated through apoptosis.
Some T cells remove cells that are infected by viruses by apoptosis. This removal is very necessary because the infection could prove to be fatal. It can grow to nearby cells and might cause the death of an organism
Introduction
Apoptosis, cancer and other diseases
Cells responds to DNA damage or other such mechanism by producing p53. p53 is a natural inducer of apoptosis in cell. In cancer cells, a
mutant form of p53
is present which results in the production of a non-functional protein. This induces a lethal threat in cells.
mutation,
Virus Associated Cancers

Human Pappilloma virus (HPV)
Epstein-Barr virus (EPV)

Non Viral Apoptopic Resistance
Cells without virus may even express resistance to apoptosis.
in B-cell Leukemias, cell produces high level of BCL-2, thus blocking signals to induce apoptosis.
Treatment:
Most cytotoxic treatments and chemotherapy, as well as radiotherapy ultimately kill cells by causing irreparable
losses to the DNA
which induces apoptosis.
Moreover some treatments
repair p53
gene to induce p53 production which then sends signals for apoptosis.

Apoptosis can also lead to other chronic diseases like Alzheimer’s disease and Parkinson’s disease. These diseases can prove to be
fatal
.



Apoptosis in adult brain and apoptosis in developing brain share a similar mechanism in the effector or executioner phase of the process, but the key difference lies in the mechanism of apoptosis induction. Toxic release resulting from biochemical or genetical accidents might trigger neurodegenerative diseases by co-opting apoptotic signalling pathways, either through free-radical generation or caspase activation
Apoptosis, tissue transplant and the immune system
Immune response to foreign invaders involves the proliferation of lymphocytes. These lymphocytes are B cells or T cells. But after the infection has been treated, these cells are needed to be degraded immediately.
This is done by apoptosis
. But in certain conditions
mutation
may occur in apoptosis. This leads to
ALPS (Autoimmune lympho proliferative syndrome)
which cause the accumulation of lymphocytes in lymph nodes especially in spleen. These form clones which cause autoimmune disease.
In organ transplants,
grafting rejection
occurs by host’s cell mediated immune response. As a result, patient has to take a lot of immune-repressive drugs that inactivate host’s immune system. Thus the patient is highly prone to other diseases due to inactivation of immune system. However, if organs are made to express high level of
FasL
, then it might protect graft from attack by T cells in host’s cell mediated response. If this works properly then present need for taking immune-repressive drugs for the rest of host’s life might be reduced or in some cases it might ultimately be eliminated.


FasL are ligands which bind to Fas(natural inducers of apoptosis).When antigen containing Fas binds to these ligands, apoptosis is induced in the antigen.
Cells are balanced between life and death
Proapoptopic proteins
Antiapoptopic protiens
Death signal
Damage
physiological death signal
Proapoptopic protiens
Antiapoptopic protiens
Intrinsic pathway(mitochondrial pathway)
Initiated within the cell
Alters functioning of mitochondria and ER
Relies on activity of BCL-2 proteins

BAK and BAX cause
MOMP

Extrinsic pathway

Apoptosis in plants
Interesting fact: The term apoptosis originates from the plant kingdom, literally meaning the falling of leaves in Greek.
Like in humans, apoptosis is very significant in plants as well.
Apoptosis in plants is involved in the reproductive period.

a. Un-pollinated flowers are fully thrown away. Ovaries with fertilized egg cells in ovules on the same plant are retained, forming fruits while the other parts; petals, sepals fall off due to apoptosis.

b. Apoptosis is involved in the formation of female gametes in seed plants.

c. Apoptosis is also involved in the formation of male sexual organs. Layer which is surrounding the pollen during maturation undergoes apoptosis.

d. Apoptosis also occurs during the
embryogenesis
in plants. Cell death within the embryo does occur as part of its normal development.

e. Apoptosis occurs during the
germination of plants
and it is also formed in the seed storage tissues.

f . Endosperm supplies nutrients to the embryo for development and germination and undergoes PCD.

Xylogenesis
: Tracheal elements (vessels/tracheids) are composed of a series of hollow dead cells. After the formation of secondary walls tracheal elements lose their cellular contents to become empty dead cells because of apoptosis.
The continuous growth of the stem is also because of Cell division in the cambium layer causes cell death in the cork layer that is replaced with the ruptured epidermis and also in parenchyma cells at the stem pith
Comparison between apoptosis of plants and animals
Mitochondrial morphology is an indicator of apoptosis in both plants and animals
The cell wall in plants is responsible for providing structure and support
The cell wall of the plant cells may act as physical barriers preventing the recycling of cellular material from dead cells via apoptotic bodies.
The dying cell synthesizes substances to break itself down and places them in a vacuole that ruptures as the cell die
Plants
Animals
mechanism of PCD not completely known
Expression of caspases is reported in some cases, but not exclusively during cell death.
Bcl-xL does not suppress PCD.
Cell corpses persist due to the persistence of cell wall
Condensation and shrinkage of cytoplasm noticed, but not fragmentation.
mechanism of PCD known
Effector caspases are activated and expressed.
BCl-xL suppresses PCD at least in some cells
Cell corpses are engulfed and eliminated through phagocytosis by neighbouring cells or macrophages
Cytoplasmic condensation, shrinkage and fragmentation are always noticed.
"No one wants to die. Even people who want to go to heaven don't want to die to get there. And yet death is the destination we all share. No one has ever escaped it. And that is as it should be, because Death is very likely the single best invention of Life. It is Life's change agent. It clears out the old to make way for the new." - Steve Jobs
.
Group Members:


Kamran Tariq
Asadullah Ghalib
Abdur Rehman
Muhummad Suleman
Mustafa Hussain Mehkary

Cell death, along with growth and differentiation, is a critical event in the life cycle of a cell.
It is very important in maintaining
homeostasis
in the body of an organism.
The fate of a cell is often predetermined, or sometimes it is affected by physiological events. From birth to death of an organism, billions and billions of cells are formed, that also die.
Thus a balance is maintained between the formation and death of a cell
Causes cervical cancer.
Binds special proteins to
p53
promoter.
Inactivate p53 production and eventually apoptosis.
Virus makes host cell to produce viral BCL-2 Protein.
Suppresses the production of p53.
Increased chances of apoptosis inhibition.
QUESTIONS?
1. Many drugs have been made in which programmed cell death is induced by introducing apoptosis inducing factor.

2. Cancer chemoprevention, which is defined as the use of natural or synthetic chemical agents to reverse or suppress carcinogenic processes, is an important strategy to reduce the risk of cancer. Many natural cancer chemopreventive compounds are known to induce apoptosis. At the molecular level, dietary chemopreventive compounds can modulate a number of key elements of cell signal transduction pathways involved in the apoptotic process.
1. Increased apoptosis is characteristic of AIDS.

2. Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis.

3. Autoimmune diseases such as hepatitis and graft versus host disease.

4. Modulation of apoptotic processes may thus offer valuable methods of treatment. It is now known that many existing drugs (for example, non­steroidal anti­inflammatories) act by altering the levels of apoptosis.
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