The Biological Mechanism of the Term Apoptosis - Essay Example

? The Biochemistry of Apoptosis The Biochemistry of Apoptosis The term apoptosis is a term which is used to describe the normal death of a living cell in living organisms. This is a normal and constant process since the living organisms function when new cells are born and they generate and the old cells or selected cells die. This is considered as a normal and daily process of a human body. For example human embryos have more cells than the human adults. The embryo develops and some selected cells are executed because of which normal development takes place. Thus, when the cells don’t pass through apoptosis, they may face deformity in the embryo and its growth. The term apoptosis can’t be confused with the term necrosis which refers to the death of a cell due to some disease or infection. Basically, apoptosis is a part of the functioning of the cell in an organism. When these functional processes are incomplete, it can lead to the occurring of tumors such as benign and malignant. Every day, about 50 to 70 billion cells die because of apoptosis in an average adult. For the children, approximately 20 to 30 billion cells die each day. Research has also increased since the past two decades on apoptosis and its importance has become a biological phenomenon as the defective processes have been resulted in a variety of diseases. Excessiveness of apoptosis causes atrophy and an insufficient amount of processes can result in uncontrollable cell proliferation such as cancer (Taylor, 2006, p. 138). Apoptosis usually has several distinct stages. The cell starts to shape into a round in the first stage of the process due to the protein present inside the cell being eaten by enzymes that are active. In the next stage, the DNA which is in the nucleus comes apart and starts to shrink. Consequently, the membrane that surrounds the nucleus also begins to degrade and does not form the usual layer then. Since the cell nucleus is not protected anymore, the DNA breaks down in uneven fragments. This makes the nucleus break down into several bodies that has uneven values of the DNA. Blebbing is the process under which the cell itself goes through and its parts begin the break down. Finally, the cell breaks down into pieces completely and it is then consumed by the small cells called phagocytes. If this last step of the phagocytic digestion is not completed in the process, it can cause danger. The cell fragments that are left undigested accumulate in the body and it is shown that they can cause death in mouse embryos and mouse neonates (Green, 2011, p. 37). Apoptosis occurs because of two types of signals, intrinsic and extrinsic. Intrinsic signals are those that occur inside a cell and extrinsic are those that occur outside the cell. When it occurs because of the intrinsic signals, it may be because of the lack of sufficient nutrition provided to the cell or the damage to the DNA present in the nucleus. The extrinsic signals occur as a result of a responsive virus or due to some treatments such as chemotherapy. The cell may also sometimes initiate the process itself in order to fight a virus like HIV. The study of apoptosis has however, become very important as it leads to the understanding of the cell death and how the process works. This helps in the further study about the stem cells and their implications in medicine. Philosophers had spent many years in searching the meaning of life, but in the recent decade, the cell biologists have become more interested in the meaning of death. As mentioned earlier, apoptosis is described as the collapse of a cell after many steps of process. These observations were made in the 1972 but they were underestimated and their importance was ignored for many years. But in the present day, apoptosis is implied in the biological processes that range from the embryogenesis to ageing and from the normal tissue homeostasis to the human diseases, and has also become a focal point in the biomedical research. As we talk about the biological mechanism of the term apoptosis, it is often used for the programmed cell death. In a more strict sense, the programmed cell death may also be applicable to the other forms of cell death requiring the gene expression without the fulfillment of the morphological criteria of apoptosis. Regardless of what the definition shows, the studies clearly show that the apoptosis is regulated genetically. The models of apoptosis show that the stages are considered as initiation, regulating genetics and effective mechanisms. The initiators may include the anticancer drugs, ultraviolet irradiation and gamma, deprived survival factors like interleukin-1 and other various cytokines that work to activate the death receptors such as Fas and tumor necrosis receptors. With the help of several pathways, the stimuli in return generate a characteristic pattern of the gene expression (Brady, 2004, p. 68). The mechanisms of apoptosis are considered to be very complex and highly sophisticated as they involve the cascade of molecular events that are dependent on energy. Till now, the research indicated that two apoptosis pathways are the main ones but there is, however, evidence that these two pathways are linked and the molecules of one pathway may influence the other. Thus, there is an additional pathway which involves the T-cell mediated cytotoxicity and the perforin-granzyme dependant killing of the cell. The perforin-granzyme pathway is able to induce the apoptosis via granzyme B or granzyme A. the granzyme B pathway converges on the same terminal as extrinsic and intrinsic pathways, the execution pathway. The execution pathway initiates the cleavage of caspase-3 and it eventually results in the DNA fragmentation, degradation of cytoskeletal and the nuclear proteins, the cross linking of the proteins, formation of apoptotic bodies, expression of ligands for phagocytic cell receptors and lastly the uptake by phagocytic cells. Apoptosis process is controlled by the diverse range of cell signals originated through extracellular or intracellular signals. The extracellular signals include toxins, hormones, nitric oxide or cytokines that cross the plasma membrane to in effect a response. The signals can affect the apoptosis either positively or negatively. The intracellular apoptosis singles are initiated in a cell as a response to stress bringing about the cell suicide. The nuclear receptors are bound by radiation, heat, viral infection, nutrient deprivation and increased calcium concentration inside the cell. Many cellular components also help in regulating the apoptosis process. The actual process of the cell death includes the apoptosis signals causing the regulatory proteins to start the apoptosis pathway even before it is precipitated by the enzymes. This initial step would allow the apoptosis signals to result in cell death or would allow the process to stop so that the cell would no longer need to die. Despite having several proteins involved, there are two main methods for regulation and they are targeting mitochondria functionality or the use of adaptor proteins as direct transducers of the signals to the apoptosis mechanism (Wilson, 2004, p. 28). The mitochondria regulation is important for the multi cellular life and in their absence, a cell may cease to respire aerobically and then it quickly dies. This fact is the basic formation for the apoptosis pathways. The proteins target the mitochondria and affect them in many different ways. The apoptosis proteins cause the mitochondrial swelling by forming membrane pores or by increasing the permeability of the membrane and this may cause the effectors to leak out. This is closely linked to the intrinsic pathways, and the tumors may frequently arise through these rather than the extrinsic pathways because they are more sensitive. A 1999 research study also shows evidence that indicates that nitric oxide can induce apoptosis by dissipating the mitochondria membrane and makes it more permeable. The mitochondrial proteins are SMACs which mean small mitochondria-derived activator of caspases. They are released in the cytosol increasing the permeability. Cytochrome c is released due to the channel formation of MAC (mitochondrial apoptosis-induced channel) which is in the outer membrane of the mitochondria. Its function is to regulate by preceding a morphological change related to the apoptosis. When the cytochrome c is released, it then binds with the apoptotic protease activating factor which further binds into procaspase-9 creating apoptosome which is a protein complex. Mitochondrial dyes of other types can also be used to measure the metabolic activity in the cells. These dyes do not relate to the mechanism of the cell death and are used in conjunction with the other apoptosis detection methods like a caspase assay (Pickens, 2007, p. 19). The direct signal transduction has two theories of the apoptosis mechanisms, these are the TNF-induced model and the Fas-Fas ligand-mediated model and both these involve receptors. The TNF is a cytokine which is produced by activated macrophages and it is the major extrinsic mediator of the process. Most of the cells in human body have two receptors: TNF-R1 and TNF-R2. The relation between the TNF receptors and the apoptosis shows the reason of the abnormal production and why is plays a significant role in human diseases especially in the autoimmune diseases. The Fas receptor binds the transmembrane protein of the TNF family (Lin, 2000, p. 490). Even though the process of apoptosis was morphologically different from necrosis, it was introduced about 26 years ago but the mechanism of the process and its initiatives have remained unclear still. The progress in these studies has been made in the last five years and in fact, tremendous development of the concept is made to enhance the understanding and application of apoptosis. There has been a molecular identification of its key components to find out the inner cellular program. The cell suicide program and its core is an evolution conserved from worm to human. There are three major components that it consists of, these are: Bcl-2 family proteins, caspases belonging to the family of cysteine proteases which is used to cleave the aspartic acid residues, and thirdly the Apaf-1/CED-4 protein which relays the signals which integrate by Bcl-2 family proteins to the caspase. These components of the cell death program are biochemically activated and are responsible for morphological changes which are observed in the process of apoptosis, including the mitochondrial damage, DNA fragmentation, nuclear membrane breakdown, forming of the apoptotic bodies and the chromatin condensation. Caspase plays an important role as they are proteins which are highly conserved and cysteine-dependent. There are two types of caspases; initiator caspases and effector caspases. Caspases are expressed in an inactive proenzyme form in the cells and once it is activated, it can often activate the other procaspases. Procaspases may also aggregate and autoactivate. The proteolytic cascade amplifies the apoptosis signaling and leads to the rapid cell death. Caspases are able to cleave the proteins at aspartic acid residues even though the different caspases have some different specificity that involves recognition of the neighboring amino acids. Once the caspases are activated, there is an irreversible commitment towards the cell death. Up till now, there are ten main caspases that are identified and are broadly categorized as initiators: caspase-2,-8,-9,-10, effectors or the executioners: caspase-3,-6,-7 and the inflammatory: caspase-1,-4,-5. Caspases are essential in the cells for the process of programmed cell death and in the development stage of adult life; they are termed as the executioner proteins in the cell. Caspases are also required for the immune system to mature the lymphocytes. The failure of the process of apoptosis is the main contribution towards the tumor development and immune diseases. When the caspase-3 is activated, it is regulated and the activity kills the cell indiscriminately. The caspases enzyme does not directly kill the cell but initiates the process of apoptosis. It can activate the process with an apoptotic signal. Once it catches the signals and initiates the process, the mechanisms of apoptosis are carried out programming the cell death (Gerl, 2005, p. 268). Cell death is a process which exists in our genetic code. But why is it that we are programmed to die? Many reasons explain why a cell should be programmed to death at a certain point. For example, in the development stage, the human fetuses have tissues that create some webbing between our fingers. As we grow, these tissues undergo apoptosis and ultimately our fingers come into form. The programmed cell death also combats cancer and is defined as the uncontrolled cell growth where a cell turns cancerous but still has a life span like that of any other cell and will eventually die. The drugs used in chemotherapy accelerate this process and trigger the process of apoptosis in the cancerous cells (Elmore, 2007, p. 501). There are many genes involved in controlling and dividing the cells. The way the cell cycle takes place is the cell’s way to replicate itself in a step by step and organized manner. The process can have a tight regulation which makes sure that the DNA of the dividing cell is copied and prepared properly to repair any errors seen in the DNA and to ensure that each cell gets the full set of chromosomes. There are restriction points for the cycle and they allow the genes to check for errors and mistakes to halt the repairs of the cycle when something goes wrong. At times, a cell may have errors in the DNA that cannot be repaired thus causing programmed cell death or apoptosis. The body will get rid of the cells that it no longer needs. Cells undergoing the process of apoptosis break apart and they are recycled by white blood cells called macrophage. The process of apoptosis functions to protect the body by removing the cells that are damaged genetically and could lead to cancer and also has an important role in developing the embryo and maintaining the adult tissues as mentioned. The cancer forms from the disruption of the regulation of the cell cycle. When the cell cycle proceeds without any control, the cell undergo an uncontrollable division and accumulate the genetic defects that may lead to a cancerous tumor. The cell death is the result of the signals that come from inside and outside the cell. At a certain point, the cells may stop receiving the hormones and proteins that it needs to function and sustain the damage to stop functioning properly, then the process is triggered. The nucleus then explodes and releases the chemicals that act as signals. The released chemicals attract the phospholipids which engulf the cell fragments and degrade the individual chromosomes and carry them as waste out of the body. The programmed cell death is a component of health and disease which is initiated by the various physiologic and pathologic stimuli. Understanding the various mechanisms of programmed cell death at the molecular level will provide a deeper insight into the various disease processes and may also influence the therapeutic strategy. The cancer cells in the body are grown uncontrollably. These cells are immortal and they are subjected to an infinite number of divisions until they reach a certain limit or get old. Cells that undergo the apoptosis process decide to kill themselves because it is of o further use. The cancer cells are less prone to apoptosis and the mutations in the DNA of these cells make them lose their ability to function. Thus, when the cell loses its ability for the process of apoptosis, they start to grow uncontrollably and start dividing which causes tumors and more possibly cancers (Strange, 2001, p. 189). Studies have shown that it is immensely important for the cells to go through the process of apoptosis and the failure of the process may cause cancer to develop. It has been identified that there is an extraordinary need for us to increase our understanding of the apoptosis and its contribution towards cancer and the cancer therapy. Although there is much more towards the apoptosis that the scientists are looking into, the avenues for the cancer diagnostics, prognosis and therapy are an important sector to understand. The system of apoptosis is very effective in the defense mechanism of cancer since the genetic defects take place in the early stages of the cancerous process. Apoptosis is the most safe and natural way of ending the malignant or pre-malignant cancer cell. A cancerous cell can become dangerous when it develops a way to override the program that leads to apoptosis. Interfering with the process of apoptosis and its pathway is the most direct approach used by a cancer to override the protective process. All the cells in the human body will die from apoptosis through which cells suicide. Cancer may often occur when the balance of the cellular process is disturbed. This may happen because of the increase in cell proliferation or the decrease in cell death. The cancer therapy has the goal to promote the cancer cell deaths without causing damage to the normal cells. The mechanisms of apoptosis have enabled our understanding that how the cancers originate and develop. It has also revealed how existing cancer therapies may work in two ways: induction of apoptosis and direct toxicity. In some of the cases it has been seen that the resistance to apoptosis process explains why the cancer therapies fail (Renehan, 2001, p. 1536). The human body is made up of 60 trillion cells and as they live, day by day, they produce new cells and division takes place. When new cells are born every day, some old ones or aged ones commit suicide, or kill themselves. This is the process of apoptosis which is essential in every living organism to keep it living. If new cells aren’t produced, there will not be any growth in the living organisms. The cells that do not function properly anymore tend to kill themselves and move out of the body. There are many signals that the cell may get in order to decide whether they are receiving enough proteins or not. This is a continuous process which replaces the damaged cells with the healthy ones. Apoptosis is also a defense against cancer as the recent researches have proved and the cells that fail to undergo the process of apoptosis may be caught by several diseases such as cancer. The cancerous cells are those that become immortal and are not removed out of the body. Such cells then start dividing and are unhealthy for the body. Thus, this is why it is important to make sure that the process of apoptosis in the body is taking place and working properly. References Brady H. 2004. Apoptosis Methods and Protocols. NJ: Springer Elmore S. 2007. “Apoptosis: A Review of Programmed Cell Death” Toxicol Pathol, 35 (4), pp. 495-516 Gerl R. 2005. “Apoptosis in the development and treatment of cancer” Carcinogenesis, 26 (2), pp. 263-270 Green D. 2011. Apoptosis: Physiology and Pathology. Cambridge: Cambridge University Press Lin A. 2000. “Apoptosis in Cancer” Carcinogenesis, 21 (3), pp. 485-495 Pickens C. 2007. Cell Apoptotic Signalling Pathways. NY: Nova Publishers Renehan A. 2001. “What is apoptosis, and why is it important?” BMJ, 322 (7301), pp. 1536-1538 Strange R. 2001. “Early stages of p-53 induced apoptosis are reversible” AMC Cancer Research Centre 8 (2), pp. 182-191 Taylor A. 2006. Cell Apoptosis and Cancer. NY: Nova Publishers Wilson J. 2004. Apoptosis: The Life and Death of Cells. 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