Apoptosis or Cell Death

Introduction

Can you ever imagine what happens if every cell that our body generates remain uncleaned? We would have been massive than any other organism. Our body is just like our environment, developing garbage in the form of redundant and used cells. This needs cleaning on a regular basis, failing which would result in a lot of unhealthy and toxic cells being accumulated. One might feel what if every cell is being cleaned? How can we survive? well, there is nothing to worry as the cleansing of old cells gives way to the birth of new cells. Therefore, every living entity constrains to periodically clean the body by destroying the redundant and old cells while replacing them with young and active ones. This is made possible by a natural and sustainable process, apoptosis. The term apoptosis is derived from the Greek origin meaning dropping or falling off. "Apoptosis or cellular suicide is the term used to describe the natural biological process of programmed cell death in which our cells undergoes self-destruction leaving behind the new and fresh cells necessary to maintain  the smooth functioning of the body.” It was first introduced by Kerr, Wyllie, and Currie.

 

Need for apoptosis

On a daily basis, 50 – 80 billion cells die off due to apoptosis. The process helps to eliminate the non-functional, and aged cells during the course of growth and development of an organism nevertheless, it continues for a whole life. It also eliminates pre-cancerous, and infected cells whereby our bodies maintain a unit of balanced and healthy cells, which is particularly important to keep our immune system in check. Most of us doubt why do our bodies form millions of unused cells? The answer is pretty simple,  tissues and cells undergo periodic wear and tear due to day-to-day biological activities. Consequently, a lot of dead cells are formed. It is a normal process, as our body needs deliberate destruction of old cells in a systematic and healthy manner. To ensure this, apoptosis takes a definite course, failure to comply with proper and systematic cycle can sometimes affect our body adversely. Apoptosis is a programmed instruction by our body, due to which the moment a cell is no more useful, it dies and a new cell is simultaneously formed. Adding to this, programmed cell death plays a vital role in the gamete maturation as well as in embryogenesis. During the phases of embryogenesis, apoptosis ensures the appropriate formation of various organs and structures. Let us explore in detail about the whole mechanism of apoptosis in this post. 

 

Changes during apoptosis

1. Physiological changes

A number of morphological adjustments occur in the body due to growth and development.  Normal growth occurs due to periodic cell division and multiplication, which is possible due to apoptosis. The process involves a lot of changes in the nuclear and cytoplasmic composition of cells, therefore, it takes up to some hours to finish things. Markus, a biologist defined that the time needed between the depolarization of the mitochondria and activation of the caspase cascade is usually around 30 minutes while the late phase involving nuclear condensation, caspase activation, and formation of the apoptotic bodies can take 3 to 48 hours. Nevertheless, the time duration depends upon the cell type, the stimulus that causes apoptosis, and the apoptotic pathway.  During the process, there is a clear-cut chromatin condensation and nuclear fragmentation in addition to the sphering of the cellular shape, consequently, there is a drastic depletion of cellular volume. Chromatin condensation begins at the outer surface of the nuclear membrane, so a crescent or ring-like structure is formed outside the nucleus. The condensation process continues until the cells are broken down while leaving behind an intact membrane, the process is termed called karyorrhexis. .It is difficult to trace apoptosis in the beginning because the phagocytic cells that help in the process engulf the apoptotic cells at the very beginning.

 

 2. Biochemical changes

3 major biochemical changes observed during the course include:  the activation of caspases, DNA and protein breakdown,  membrane changes and recognition by phagocytic cells. Caspases, a unique family of cysteine proteases assist in the execution of programmed cell death. Caspases exist as inactive zymogens in cells and undergo a cascade of catalytic activation at the onset of apoptosis. The inhibitor-of-apoptosis (IAP) inhibits protein synthesis in the cells. Furthermore, the DNA is broken down into multiple pieces, sized 50 to 300 kilobase each. Adding to this, there is internucleosomal cleavage of DNA into oligonucleosomes in multiples of 180 to 200 base pairs. The process is helped by the enzymes endonucleases.

 

Difference between cell necrosis and apoptosis

A sequential wave of programmed cell death is necessary for normal development of an embryo during embryogenesis or during any cell injury and infections. Cell necrosis or death of tissues is a passive form of cell death that is induced by non-physiologic agents (not from within). The following table briefs the major differences between apoptosis and necrosis.

 

Apoptosis

Necrosis

Apoptosis is initiated by our body cells, it is a normal and routine process necessary to keep our cells healthy and refreshed .                                                                                                                                            

Necrosis is not a  normal phenomenon as it can occur only when our body cells are encountered by a dangerous situation. It is seen when pathogens and some toxins enter in. 

The process results in the formation of new cells while the old cells are shed away.

It is an irreversible process causing permanent loss of cells with no chance of replacement by the newer ones.

The cell membrane breaks into several apoptotic bodies

The cell membrane undergoes lysis to release its contents

It is an essential process to safeguard our body

Necrosis is harmful to health

Apoptosis is driven by a fixed pathway and sequence.

The sequences and pathways of necrosis depend upon the causes of necrosis.

It is one of the natural defence mechanism by our body

It is not an unusual process as it is triggered when the body suffers from infections, antigens, toxins and injuries.

It is a passive process that does not demand energy

This is an active process that consumes a lot of  energy

 

 

Apoptosis to eliminate infected and cancerous cells

 

   

 

When our body senses that a cell can pose a threat to the rest of the body, the apoptosis comes into the picture. The process is initiated with the damage of DNA in the pre-cancerous and infected cells. The moment our cells notice the damage to their DNA, they attempt to eliminate but the enzymes in action block the repair, which eventually destroys the abnormal cells. Followed by this, cell division starts. Most of us know what is a normal cell cycle and the cell division is. Cell division along with the apoptosis gradually replenish our body.  The dead tissues formed by the apoptosis are cleansed by the action of WBCs.

 

Apoptosis in animals

Some animals undergo apoptosis in an attempt to shed their outer shell containing unused cells. The snake sheds its outer layer for at least 4-6 times in a year, it is a significant process to clean their outer skin that is being accumulated with redundant cells which you might have observed in the form of a dry, scaled-skin of a cobra in the wild.  Another classic example of apoptosis is the loss of the tail of a tadpole as it attains maturity to become a frog.

 

Mechanism of apoptosis

Apoptosis is initiated by  2 separate pathways, the intrinsic and extrinsic pathways.  Intrinsic Pathway, as the name suggests, is a response to the biochemical stress, damage, infections,  cancerous cells formed within our body. On the contrary, the extrinsic Pathway is initiated as a response to some external stimulus such as a mechanical injury to the cell.  The whole process begins with the deliberate damage to the DNA which in turn activates the p-53 gene which ceases the cell cycle. Followed by this, the cell initiates the repair of DNA simultaneously. If the DNA repair fails, the cells begin to undergo induced apoptosis with the help of viruses that enter the body. By this way,  we can understand that a foreign invader enters into when our body fails to initiate natural apoptosis.

 

Apoptosis and the immune system

Apoptosis is a methodical phenomenon, it takes the help of lymphocytes and WBCs along with the apoptotic enzymes. During the process, the cell’s contents break down allowing the useless dead cells packaged into small packets of membranes and is considered as garbage.

 

 

 

Review questions        

  1. Explain the 2 pathways of apoptosis

  2. Distinguish between apoptosis and the necrosis.

  3. Why is apoptosis important?  

  4. Give one example of a natural apoptosis in animals.

  5. Explain the cellular changes during apoptosis.

  6. Define karyorrhexis.

 

 

More readings 

  1. WBCs

  2. Structure and functions of cell  

  3. Meiosis

  4. Cell cycle,


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