Discovery and Etymology of Apoptosis - Research Paper Example

Apoptosis is an important programmed cell death process which exists and occurs in in multicellular organisms. It is different from necroses, according to which traumatic cell death is a caused by acute cellular injury. In Apoptosis the advantage basically is linked with the advantages coming from organism’s life cycle. Apoptosis produces apoptotic bodies which are cell fragments through which phagocyte cells quickly remove and also engulf the content linked with the cell which can spill out in the cells which are in the surrounding which is extremely harmful. In an average human being almost 50 to 70 billion cells and in a child about 20 billion to 30 billion are damaged and they die due to apoptosis in a single day. It is not just a biological phenomena , all the defective apoptotic processes are linked with a lot of other diseases and also an excess of apoptosis can lead to atrophy and if the amount is less or insufficient , it can cause cancer which is due to cell proliferation (Al-Rubeai, Mohamed, and Martin Fussenegger,2004). Discovery and Etymology The process was initially described in 1842 by Carl Vogt and during the year 1885 Walther Flemming was the person who in more detail described this programmed cell death process. The difference between other traumatic cell deaths and apoptosis was identified by John Foxton Ross who was with University of Queensland at that time. There is a lot of work done by various people from Sydney Bernner, John E Sulston and even Horvitz who received Nobel prize during the year 2000 for their own apoptosis. Apoptosis is basically a multi path and multi step death program of the cells which is inherited in all the cells of the body. During the process of cancer, the cell division ratio is altered. The word apoptosis is taken from a Greek word which means the “dropping off” of the leaves and petals from the trees and also plants. The term was reintroduced by Professor Cormack of Greek language for medical usage. Process Different range and variety of cell signals control the process of apoptosis which originates intracellular and sometimes even extracellular signals. The extracellular signals include hormones, nitric oxide, hormones, cytokines and also various growth factors which are transduced through the effect of a response and sometimes crossed through the plasma membrane. These signals can have negative and also positive impact on the apoptosis. There are positive and also negative inductions, when the active repression and also inhibition of apoptosis occurs through a molecule that is negative induction; where as the triggering and binding of the apoptosis through molecule is the positive induction. Stress is the major factor which makes the cell initiate intracellular apoptotic signaling which causes cell suicide. Various factors results in regulating apoptosis, which include poly ADP ribose polymerase. The cell death is caused through the enzymes and before that there are apoptotic signals which enable the regulatory proteins to instigate the pathway of apoptosis. Mitochondrial regulation Mitochondria are important and crucial factor linked with the multi cellular life because in its absence the cell is ceased and thus it will not be able to respire aerobically and it will quickly die. This is the major cause of the apoptotic pathways. Mitochondria is targeted by the apoptotic proteins in various ways which can cause the swelling of mitochondria which causes the formation of the membrane pores and they also increase the mitochondrial membrane permeability and it can also be a major reason of leaking out of the apoptotic factors. Apoptosis is activated through the nitric oxide which initiates the possible action of a signal molecule linked with the succeeding pathway. Mitochondria releases cytochrome which formed a channel known as mitochondrial apoptosis induced channel which is available in the outer part of the mitochondrial membrane which can also serve the regulatory function and it is also linked and associated with the change of morphology which has a relationship with apoptosis. Direct signal transduction There are two theories linked with the direct initiation of the apoptotic mechanisms which are present in the mammals and they also suggested by Fas Fas ligand mediated model and also induced through the tumor necrosis factor which is involved in the reception of receptor family joined through extrinsic signals. TNF path It is the cytokine which is produced through the activated macrophages and it is also the major extrinsic arbitrator of the apoptosis. There is a close association of TNF with apoptosis which shows abnormal production of TNF which is a crucial element in various human diseases like autoimmune diseases. Common components There is a proper proportion of proapoptotic homodimers required to form the outer membrane of the mitochondria and it also helps in making the mitochondria membrane permeable for the caspase activator release which includes SMAC and also cytochrome. Caspases Apoptotic signals are majorly triggered by the caspase which are the proteins being highly conserved along with cysteine dependent aspartate proteases which are extremely specific. There are basically two kinds of caspases which include the effector caspases which are caspase 3,7,6 and also initiator caspases which include caspase 8,10,9,2. There is an activation of the initiator caspases linked with specific oligomeric protein adoption. Caspase independent apoptotic pathway This pathway exists in caspase independent apoptotic pathway which is mediated through the apoptosis inducing factors. Execution There are various signals and pathways which lead to apoptosis but it is linked with only one mechanism which causes the cell death. The process starts when a stimulus is received by the cell and it started to organize the degradation of the cellular organelles which is basically activated through the proteolytic caspases. The process of apoptosis is attempted on a cell which is linked with various morphologies which include the shrinkage of cells and the surrounding which is the result of the breaking down of the proteinaceous cytoskeleton which is through the caspases. This causes the cytoplasm to become dense and also the organelles to become tightly packed. The chromatin becomes condensed which thus contain compact patches against the nuclear envelope called perinuclear envelope through the process which is a hallmark of apoptosis, pyknosis. This then results in discontinuing nuclear envelope and fragmenting the DNA which is known as karyorrhexis. There are irregular buds known as blebs which are shown by the cell membrane and also the cell breaks into several vesicles known as the apoptotic bodies which later on are phagocytosed (Preedy, Victor R,2010). Removal of dead cells Efferocytosis is the term used for the removal of the dead cells through the phadocytic cells which are present nearby. All the cells which are going through the final stages of the apoptosis and are dying basically exhibit phagocytotic molecules. Which include phosphatidylserine which is present on the cell surface (Reed, John C. ,2000).The normal position of the phosphatidyserine is cytosolic surface of the plasma membrane, however it is redistributed during the process of apoptosis to the extracellular surface through a protein which is known as scramblase (Kuchino, Y, and Werner E. G. Müller,1996). Pathway knock outs There are various knock outs which are made in the pathway of apoptosis in order to test the function of each of the proteins. There are various caspases apart from the FADD and APAF-1 which have mutated in order to set up the new phenotype. This is carried out in order to setup tumor necrosis factor knock out. It includes the exon which contains nucleotides which are removed from the gene. Some important knockouts include caspase 9 which causes brain malformation and also caspase 8 knowck down which causes cardiac failure and finally embryonic lethality (Norwell, MA,1996). Defective pathways There is a variety of apoptotic pathways which contain a multitude of various biochemical components which are not majorly understood. Different pathways are a victim of causality which remove and also modify various components leads having an effect in another. There are disastrous effects of this on the living organisms which are in the form of disorders and also diseases. An important example here is of NCI-H460 which is developed through lung cancer. There is an X linked inhibitor of the apoptosis protein which majorly over express the cells of the H460 cell line. There is an important requirement of the anti apoptotic and also proapoptotic effectors which upset and thus it leads to the damaged cells continuous replication (Schwartz, Lawrence M, and Jonathan D, 2001). Dysregulation of p53 Tumor suppressor protein p53 is accumulated through the DNA which is damaged through a chain of biochemical factors. It stops the cells from replicating by preventing the cell cycle at G1 and also interphase which provide cell time to repair and it will induce apoptosis when it is damaged through extensive and also repair efforts which totally fail. If there is an disruption to p53or even inteferone genes they will cause impaired apoptosis and also possible formation of tumors (New York: Cold Spring Harbor Laboratory, 1991). Inhibition The apoptosis inhibition causes a number of cancers, inflammatory diseases, viral infections , autoimmune diseases and also cancers. Hela cell Apoptosis in Hell cells is repressed by the proteins which are produced through the cells which have inhibitory proteins which target retinoblastoma tumor which suppresses the proteins (Scovassi, A., 2005). Treatments Inhibition of excess apoptosis is the remedy of the death causing diseases which involve decreased and also increased apoptosis in the diseased cells (Liebermann, D A. ,1998). All the treatments which inhibit apoptosis work in order to restrain proapoptotic factors. Hyperactive apoptosis In excess apoptosis there is loss of cell death control which causes hematologic diseases along with neurodegenerative diseases and also tissue damage (Jacobson, Michael D, and Nicola J. McCarthy, 2002) HIV progression It is a mechanism linked with T helper cells which causes depletion known as apoptosis which is due to a series of biochemical pathways (Mihich, Enrico, and Robert T. Schimke, 1994). Viral infection The apoptosis viral induction causes several cells in a living organism to get infected which then leads to virus which can cause cell death. Death of the cells in the organisms is important and necessary for the development of the normal cells along with the cell cycle maturation. Viruses like this can cause apoptosis of infected cells through various mechanisms like activation on protein kinase, receptor binding and also interaction with p53 (Wyllie, A H, 1997). References Al-Rubeai, Mohamed, and Martin Fussenegger. Apoptosis. New York: Kluwer Academic Publishers, 2004. Internet resource. Reed, John C. Apoptosis. San Diego, Calif: Academic Press, 2000. Print. Apoptosis. Norwell, MA: Kluwer Academic Publishers, 1996. Internet resource. Schwartz, Lawrence M, and Jonathan D. Ashwell. Apoptosis. San Diego, CA: Academic Press, 2001. Print. Jacobson, Michael D, and Nicola J. McCarthy. Apoptosis. Oxford, OX: Oxford University Press, 2002. Print. Preedy, Victor R. Apoptosis. Enfield, NH: Science Publishers, 2010. Print. Mihich, Enrico, and Robert T. Schimke. Apoptosis. New York: Plenum Press, 1994. Print. Kuchino, Y, and Werner E. G. Müller. Apoptosis. Berlin: Springer, 1996. Print. Wyllie, A H. Apoptosis. London: Published for the British Council by the Royal Society of Medicine Press, 1997. Print. Scovassi, A I. Apoptosis. Karala, India: Research Signpost, 2005. Print. Liebermann, D A. Apoptosis. Basingstoke, Hamshire, UK: Stockton Press, 1998. Print. Apoptosis: [1]. New York: Cold Spring Harbor Laboratory Press, 1991. Print. Read More