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Molecular Targets and Drug Design: Apoptosis - Essay Example

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Apoptosis also defined as programmed cell death or physiological cell death that occurs as a result of a deliberate activation of the constituent genes, whose main function is to cause its own death. It is a series of Biochemical events lead to change in the cell morphology followed by cell death. …
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Molecular Targets and Drug Design: Apoptosis
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Download file to see previous pages It is a series of Biochemical events lead to change in the cell morphology followed by cell death. Characteristically these morphological changes includes, the aggregation of chromatin together with cytoplasm and nuclear condensation into a distinct membrane bound vesicles which are known as Apoptotic Bodies, there is chromosomal DNA fragmentation, shrinkage of cell and cell blebbing (which are intact membrane vesicles). There is no inflammatory response, the cellular blebs and remains are quickly phagocytysed by the macrophages and the adjacent cells. (Kumar and Clark, 2005). In an average adult human about 50-70 billion cells die in one day in various tissues like intestines and bone marrow, while approximately 20-30 billion cells die each day in an average child of about 8-14 years. These dead cells are replaced by the new ones. There are 100 trillions cells in our body which are members of a highly organized community which efficiently controls both the cell division and cell death. In simple when a cell is no longer of any use or it become a threat to the body then it undergoes a suicidal programmed cell death mechanism called apoptosis. (Hall and Guyton, 2006). German scientist named Carl Vogt in the year 1842 was the first one to define the main principle of apoptosis. Research about apoptosis has increased greatly since early 1990’s. If apoptosis occurs in excess it results into atrophy while if it is taking place insufficiently then it causes an uncontrollable cell proliferation resulting in cancer. In contrast to Necrosis (traumatic cell death) where the cell swells up due to injury resulting it to burst and spills its contents, resulting in inflammation and injury to an adjacent cells. The process of apoptosis involves a particular proteolytic cascade that causes the cell to shrink become condense, loose its cytoskeleton , alters the cell surface in order for the neighboring phagocyte cells such as macrophage to attach itself to the cell membrane and engulf the cell before the contents spills, thus leaving the adjacent cells healthy.(Hall and Guyton, 2006 ). The process of apoptosis needs energy in the form of Adenosine tri phosphate (ATP) and many Ca+2 and Mg +2 dependant nuclear system are activated which specifically splits the nuclear DNA at inter-histone residues. The endonuclease destroys the DNA following the apoptosis This process involves an enzyme called as CASPASE ( Cysteine-containing Aspartase- Specific Protease) this enzyme is synthesized within cell and stored in it in the form of pro-Caspases, this enzyme once activated result in the cascade of break down of proteins within the cell. Caspase in turn activates the CAD (Caspase DNase) / ICAD( inhibitor of CAD) system that can cause DNA destruction.(Kumar and Clark, 2005) The cells then detach it self and its remains are rapidly eaten up by the adjacent phagocytic cells. There are two main signaling pathways that starts the process of apoptosis :Extrinsic pathway, that is initiated by the death receptors on the surface of cell, these signals include toxins, hormones, growth factors, cytokines and nitric oxide, they either cross the plasma membrane or transduce in order to produce a response. These signals may either trigger or repress the apoptosis. While the Intrinsic pathways initiates at the mitochondrial level. The cell starts intracellular pathway in response to the following trigger’s , stress that may result in cell suicide, binding of the nuclear receptors by glucocorticoids, nutrition deprivation, viral infection, heat, radiation, hypoxia and increased level of intracellular calcium. The Extrinsic Pathway helps in the process of tissue remodeling and to induce immune self tolerance. Now the activated receptors containing internal death ...Download file to see next pagesRead More
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