Apoptosis (Greek: apoptosis - leaf fall) is a process of programmed cell death, it is a completely natural phenomenon that allows you to remove abnormal, damaged and used cells from the body. It is worth finding out what exactly it is, whether apoptosis is a harmful phenomenon, when it occurs and what processes lead to it.
Contents:
- Initiating apoptosis
- Course of apoptosis
- Apoptosis control
- Apoptosis and disease
Apoptosisis a physiological, natural process that runs continuously in every he althy organism, it is essential for the proper functioning of the organism. Thanks to apoptosis, the body has the ability to control the number and quality of cells. This process, known as programmed cell death, leads to the elimination of damaged, infected or unnecessary cells, which ensures a balance between the formation of new cells and the destruction of old cells.
Disorders in the course of apoptosis have a very negative effect, there are diseases whose prevention and treatment are very difficult - cancer, autoimmune diseases. Perhaps new methods of treatment that enable the process of apoptosis in cancer cells will become an effective treatment.
The total number of cells in the body is strictly determined and constant, any longer-lasting change in their number can have a negative impact on our he alth, therefore the body strives to maintain a balance between the destruction of cells and the formation of new ones. The cell death process can occur in several ways, the most important of which are:
- Necrosis (necrosis)- is caused by external factors: chemical, mechanical, physical. It is a pathological, abnormal process over which the body has no control. In its course, whole groups of cells are destroyed, and the consequence of this damage is the development of the inflammatory process.
- Apoptosis (programmed cell death)is completely different, the process is completely normal, physiological, single-cell and essential in a normally functioning organism.
- Autophagy- consists in digesting the cell by its own enzymes.
Despitenegative overtone, apoptosis is a normal phenomenon, taking place regularly, it is aimed at the good of the whole organism, allowing the replacement of inefficient, worn-out cells with new ones. The removed cells are mainly those that could become dangerous to the host, e.g. cancerous or neoplastic.
Apoptosis allows you to maintain homeostasis, i.e. the balance of the body. The process of programmed cell death is a very complex phenomenon, involving dozens of enzymes and proteins. The time of its occurrence is also not accidental, it is determined by many signaling pathways that are activated as a result of cell damage: its organelles or genetic material.
Initiating apoptosis
The activation of apoptosis is associated with the activation or inhibition of the action of certain proteins (pro and anti-apoptotic) that are constantly present in the cell. The way the process occurs depends on the type and stimulus that triggers apoptosis. Initiation is the first, initial phase, during which the signaling pathways leading to the development of the process of programmed death are activated.
The most important of them is the so-called internal pathway, in which the dominant role is played by mitochondria and the external one, its triggers are signals from outside the cell:
- deficiency of growth factors, hormones
- increase in the concentration of some cytokines (molecules produced by lymphocytes)
- interactions from adjacent cells
- physical factors
- nutrient deficiency.
In the case of the extrinsic pathway, environmental stimuli affect receptors located in the cell membrane (the so-called death receptors), which trigger a cascade of intracellular signals leading to apoptosis.
Mitochondria play a key role in the endogenous pathway. When damaged by various factors, pro-apoptotic proteins are expressed in these organelles, which in turn damage the function of the mitochondria, preventing energy production.
In addition, this damage causes the release of a protein from the mitochondrion - cytochrome, which contributes to an increase in the concentration of calcium ions in the cell. The increase in the amount of this ion is a trigger of apoptosis.
Course of apoptosis
A cell's transition to apoptosis can be recognized by its separation from others, and is the first step in this process. It results from electrolyte shifts, dehydration of the cell and changes in its shape. Then the cell nucleus is fragmented and the so-called apoptoric bodies are formed, these are the remnants of the cell that will be absorbedby adjacent cells or "eaten" by macrophages. Such a course of apoptosis causes the cell to be removed "silently", it does not cause the development of a general reaction - inflammation.
As mentioned, various enzymes are involved in this process: caspases digesting proteins contained in the nucleus and cytoplasm, transglutaminases and endonucleolytic enzymes responsible for cutting DNA. The course of the entire destruction process (execution of apoptosis) can be divided into several stages:
1. The control-decision phase- it consists in transmitting information to the nucleus about the activation of repair mechanisms or their abandonment and the commencement of the cell decay process. Caspases, BID and BAX proteins participate in this process, and T lymphocytes release granzymes inside the cells, which, among other things, release calcium ions to stimulate apoptosis.
2. Executive phase- in this stage caspases develop their full function - they destroy cellular proteins - structural and enzymatic:
- DNA polymerase and DNA kinase, preventing the repair of nucleic acids
- lamines, damaging the nuclear membrane.
In this phase, the dehydration of the cell takes place, further changes in shape and size, DNA fragmentation (by endonuclease), then cell fragmentation and the formation of apoptotic bodies. These caspases are intracellular enzymes that cut proteins in specific places - a given sequence of amino acids. Their activation occurs in an avalanche-like manner - the activated caspase activates another one.
Interestingly, despite the breakdown of many cellular proteins, cellular organelles remain intact and find their way completely into the apoptoric bodies.
3. Theclean-up phase consists of phagocytosis, i.e. absorption of cell debris, most often by the phantom cells - macrophages.
Apoptosis control
Apoptosis is a strictly regulated process - both its initiation and its course. The control is primarily the Bcl-2 family of proteins, including anti-apoptotic proteins - they counteract the development of apoptosis (e.g. Bcl-2, Bcl-XL, Bcl-w) and pro-apoptotic - promoting its occurrence by damaging the mitochondrial membrane (Bid, Bak, Bad).
Expression or activity of these proteins depends on the conditions in which the cell is present, as well as its state - if the damage is large or the external conditions are not favorable, pro-apoptotic proteins are activated.
Under normal conditions, anti-apoptotic proteins dominate and inhibit the process of programmed cell death. In addition, it has been proven that apoptosis is also controlled by genes, one of them is the p53 gene, it belongs to the factorspro-apoptotic. Its product, the p53 protein, triggers the process of suicidal cell death if the damage to the genetic material is so severe that DNA cannot be repaired.
Hence, this protein is sometimes referred to as the "guardian of the genome" because it determines whether a cell will stop cell division to repair damage that has occurred, or whether it will apoptosis.
Apoptosis and disease
It has been proven that the imbalance between the formation of new cells and the elimination of old cells is the cause of many diseases, therefore cellular control of apoptosis is extremely important, and its disturbance can have very serious consequences.
If cells are resistant to death by apoptosis, they may develop cancer or an autoimmune disease (such as rheumatoid arthritis). In both of these cases, diseased cells do not undergo the process of apoptosis, they are "resistant" to it due to genetic mutations or abnormal activity of pro and anti-apoptotic proteins. On the other hand, excessive compliance and elimination of too many cells can lead to degenerative diseases and organ damage.
Currently tested, the latest oncological drugs act at the stage of apoptosis - the mechanism of action is to promote the presence of pro-apoptotic proteins - promoting the occurrence of apoptosis in tumor cells. Radiotherapy and "standard" chemotherapy work in a similar way to induce apoptosis. Both of these treatments cause cellular stress which kills the tumor cells. Unfortunately, such therapy is not always effective, because in tumor cells the activity of factors inhibiting apoptosis is often increased, which not only makes it difficult to fight them, but also leads to uncontrolled growth and multiplication.
About the author
Bow. Maciej GrymuzaA graduate of the Faculty of Medicine at the Medical University of K. Marcinkowski in Poznań. He graduated from university with an over good result. Currently, he is a doctor in the field of cardiology and a doctoral student. He is particularly interested in invasive cardiology and implantable devices (stimulators).