Apoptosis, otherwise known as Programmed Cell Death (PCD), is a process which allows cells to commit suicide to help aid organisms in growth and to avoid any possibilities of acquiring diseases. It eradicates cells which are no longer needed in the organism.
Although there are many types of PCD, it tends to be compared to Necrosis, but they’re used under different conditions, each having a separate, different process for cell death. Unlike apoptosis, necrosis is cell death which is not programmed. The process and the reason for apoptosis within development have been researched in numerous organisms like in tadpoles and the C. elegans worm.
It further plays a vital part in the immune system and disease which allows to keep an organism healthy. If there’s unnecessary or not enough apoptosis occurring within humans, then it can lead to many different severe disorders or diseases. Apoptosis neatly makes cells suicide without causing any damage to the surrounding cells. On the other hand, necrosis often damages and harms the nearby tissue which tends to result in the area to become inflamed. In the first stages of apoptosis, the cells would begin to shrink which therefore results in the cells to become smaller with a denser cytoplasm. Thus, the organelles within the cell become more compact and firmly packed together.
After that, chromatin condensation occurs so the surfaces of the chromatin clusters and clumps together into many different shapes. It then develops blebs because the cytoplasm blebs out, which are like bubbly-shaped lumps, onto the plasma membrane. When the blebs disconnect and buds off from the plasma membrane, they become apoptotic bodies with organelles inside. This divides the entire cell into smaller chunks. Furthermore, the organelles are the cell fragments that can be recycled through phagocytosis very quickly.
The macrophages are attracted towards the apoptotic bodies, when the signals are released, to engulf them by using its pseudopodia to surround it. While the phagocytes engulf the apoptotic bodies, the pseudopodia don’t take up any solutes. It when starts to digest the apoptotic bodies which would be inside the phagocytic vacuole that fuses together with a lysosome to make a phagosome. The apoptotic bodies will break down after the lysozymes get released from the lysosomes. As soon as the apoptotic bodies are digested, the macrophages become tingible body macrophages which can be stained.
There are several pathways in which apoptosis can be activated: the intrinsic pathway, the extrinsic pathway, and the perforin/granzyme pathway. Caspases (cysteine proteases) activates apoptosis and they start off as procaspases, which is an inactive form of caspase until they’re initialised to start killing cells. In addition, caspases can also activate other caspases by using a cascading effect. Firstly, the intrinsic pathway is also called the mitochondrial pathway because the mitochondria release Cytochrome C to activate the caspase.
It has two different types of signals in which it can be activated by. These are the positive and negative signals; the signals are sent from within the cell itself. Therefore, the signals are sent due to stress on the cell. Examples of positive signals would be ‘radiation, toxins, hypoxia, hyperthermia, viral infections, and free radicals’. Examples of negative signals would be ‘the absence of certain growth factors, hormones, and cytokines’.
The negative signals stop any restrictions that there may be of apoptosis later by destroying the cell earlier. Secondly, in the extrinsic pathway also has two ways in which they can activate the caspases which are the Tumour Necrosis Factor (TNF) and Fas. The TNF pathway includes the macrophages releasing cytokine to activate the caspases. In the Fas pathway, the ligand proteins bind to the death receptors on the plasma membrane which activates the caspases. The Death Inducing Signalling Complex (DISC) is formed within the cell also bind with the procaspases to activate them.
Lastly, the perforin/ granzyme pathway involves cytotoxic T lymphocytes (CTLs) which can cause normal cells to suicide along with ‘tumour cells and virus-infected cells’. CTLs can identify the cell by the certain molecules plasma membrane which allows it to kill the cell when cytotoxic granules are released. During growth and development, many different organisms use different types of apoptosis such as morphogenic, histogenic and phylogenetic apoptosis. For example, apoptosis plays a role in many stages of the amphibian metamorphosis climax – the development of an amphibian from an immature organism to an adult. In this process, many cells die by apoptosis to be reabsorbed which includes cells such as “epidermal cells, fibroblasts, nerve cells, and muscles”.
Many parts of the body for tadpoles, such as the tail, intestines and gills, are killed and resorbed. The Thyroid hormone triggers the process of apoptosis which then causes the tadpole to resorb the tail. During prometamorphosis, NF stage 57, amount of Thyroid hormone increases which begins the apoptosis of the muscles in the tail. The tail reduces its size the most when there’s the highest number of apoptotic cells. The most apoptotic cells appear at around stages 63 to 64. This allows the tadpole to lose its tail to mature and transform into a frog.
The C. elegans worm has been thoroughly researched and most, if not, all the stages of development are known and has helped research of apoptosis in other organisms. There are three main phases in the development of the C. elegans worm which includes apoptosis: specification, killing, and execution.
To begin with, the C. elegans worm cells are chosen to die by apoptosis in the specification phase. During the embryonic stage, it starts as a single cell and divides to 558 cells within the egg before continuing to divide in the post-embryonic stage. Whilst the worm is in the embryonic stage, 113 of its cell die via apoptosis.
Altogether, 131 cells die because 18 of them die in the larval stage. All these cells that dies during PCD has been identified. In addition, in the killing phase, this would be the moment that the cells would start to die. There are three genes that promote PCD while another gene prevents cells dying in the embryonic phase. As a result, if there is a mutation in the gene that prevents cells dying, this may cause uncontrolled cell death.
Lastly, the execution phase is the process of apoptosis. This would be when the cell starts to shrink and form blebs, the nuclear membrane is broken down and apoptotic bodies phagocytosed by macrophages. Furthermore, apoptosis is used in the immune system and diseases to make sure the organism stays healthy.
