Apoptosis -Explained

Table of contents

Keywords: 

Caspase8|Caspase9|Smac|Proapoptotic proteins |BAX| BAD BAK| Ceramide | apoptotic bodies| Apoptosis | Necrosis| Cell death|cell programmed death| Regulated cell death

Introduction: 

Apoptosis is programmed cell death. It is a well-coordinated and planned cell death procedure. Apoptosis was first described in 1972. Apoptosis is a natural process that is under genetic control.

Apoptosis is different from necrosis.

Apoptosis is derived from the Greek word meaning the falling of leaves from trees or petals. Apo is a prefix meaning “away from,” and ptosis means “falling.”  

Mechanism of Apoptosis:

Apoptosis is triggered by both internal and external stimuli.

Internal stimuli:

Apoptosis-inducing factor is present in the intermembrane space in the mitochondria. Hypoxia, lack of certain hormones, for example, growth hormone, thyroxine, and excess stress radiation cause the release of cytochrome and Smac .’Smac’ is a protein that activates ‘Caspase 9’, which in turn stimulates apoptosis.

External stimuli:

y receptors, for example, ‘TNF,’ are present on the cell membrane. Some ligands bind with their specific receptors and provoke a series of reactions leading to activation of ‘Caspase8’. The activated ‘Caspase 8’ causes DNA fragmentation and chromatin condensation. 

Steps of Apoptosis:

1. Activation of Caspases will cause proteolysis.

2. Hydrolysis of sphingomyelin of the cell membrane forms Ceramide, which causes damage to mitochondria and releases apoptosis-inducing factors.

3. Cell shrinkage

4. DNA damage

5. Liberation of apoptotic bodies and finally

6. Phagocytosis of apoptotic bodies by phagocytic cells of the body. 

Regulation of Apoptosis:

Apoptosis depends on the delicate balance between:

1. Proapoptotic proteins such as BAX, BAD, BAK, and

2. Antiapoptotic proteins, for example, BCL-2 and Bcl-xL. BCL-2 is the first apoptosis regulatory protein recognized in any organism.

There are many BCL proteins, such as BCL-2, BCL-3, BCL-5, BCL-7, BCL-9, and others.

The synthesis of BCL-2 (B-cell lymphoma-2) is controlled by the BCL-2 gene. BCL-2 is present on the outer membrane of mitochondria and inhibits proapoptotic proteins, promoting cellular survival.

Sometimes it may promote apoptosis by stimulating proapoptotic proteins. Proapoptotic proteins act on the mitochondrial membrane, promoting permeabilization and releasing factors that trigger apoptosis.

Importance of Apoptosis:

Apoptosis is a normal physiological process that occurs during an organism’s growth and development. This has a vital role in removing harmful and useless cells from the body.

Defects in apoptosis are responsible for malignancy, autoimmune diseases, and organ atrophy.

During fetal development, many tissues degenerate.

Degeneration of the web in the fingers to separate the fingers and toes.

Degeneration of neurons during brain development and formation of synapses.

Thymus involution after childhood. Endometrial shedding in the menstrual cycle. Normal shedding of the intestinal epithelium and some cells. Rejection of transplants.

Damage to the BCL-2 gene is responsible for many cancers, including cancer of the prostate, breast, lungs, melanoma, and some autoimmune diseases. It is also involved in resistance to cancer treatments.

Overactivation of antiapoptotic factors or underactivation of proapoptotic factors is responsible for the reduced cell death that is specific to cancers.

The reverse is also true. Overactivation of proapoptotic factors or underactivation of antiapoptotic factors is responsible for atrophy of organs, neurodegenerative diseases, schizophrenia, Parkinsonism, etc.

Differences between Apoptosis and Necrosis

		Necrosis	Apoptosis
1.	Cell size	swells	shrinks
2.	Cell organelle	disintegrate	Remains almost normal
3.	Cytoplasmic changes	homogenously eosinophilic	intensely eosinophilic
4.	Nuclear changes	Condensation and clumping of the nucleus.The disintegration of the nucleus.	Condensation of the nucleus and chromatin

Diagnosis of apoptosis:

1. DNA fragmentation assay

2. Cytosolic cytochrome-C, activated caspase