Apoptosis

The word apoptosis has been derived from the ancient Greek term that denotes "falling off". This term refers to a process involving the programmed death of cells occurring in multi-cellular organisms. Precisely speaking, biochemical incidents bring about morphology (characteristic changes in cells) and eventual death. Such typical changes include shrinking of cells, blebbing, condensation of chromatin, nuclear fragmentation, chromosomal DNA fragmentation as well as decay of global mRNA. It is estimated that on average anything between 50 billion and 70 billion cells die daily owing to apoptosis in an adult human being. In the case of children in the age group of 8 years and 14 years, on average an estimated 20 billion to 30 billion cells die via apoptosis daily.

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Actually, cell death occurs by two means - apoptosis and necrosis. Apoptosis is a comparatively common means of cell death, which is also referred to as "cell suicide". Although initially it may not appear to be so, apoptosis is considered to be better compared to necrosis. Firstly, the cleaning involved in apoptosis is relatively easy. Occasionally, this method is described as programmed cell death. Moreover, the process involved in apoptosis pursues a restricted and conventional routine.

On the other hand, necrosis takes place when an external source like poison damages a cell. In addition to poison, the external source may also be an infection, a physical injury or even the blood circulation being cut off, which may happen during a stroke or a heart attack. When cell death occurs due to necrosis, it is a somewhat disorderly condition. Cell death via this means leads to inflammation, which may result in additional injury or distress inside the body.

Contrary to necrosis, which is basically a type of harrowing cell death resulting from severe cell injuries, apoptosis is a very controlled and regulated process that has several advantages during the lifecycle of an organism. For instance, when the fingers and toes of a developing human embryo separate, it is attributed to apoptosis between the digits. Different from necrosis, apoptosis also creates cell fragments known as apoptotic bodies, which are engulfed by phagocytic cells and removed quickly even the contents of these cells are able to leak out on the neighbouring cells and damage them.

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Once apoptosis begins, it cannot be stopped and, therefore, it is a very controlled process. There are two pathways through which apoptosis can be initiated. The first one, called intrinsic pathway involves a cell killing itself, as it feels cell stress. In the second pathway, called extrinsic pathway, the cell destroys itself after receiving pointers from other cells. However, in both these pathways, cell death is induced by triggering caspases, which are basically enzymes or proteases that break down proteins. Both the pathways set in motion initiator caspases, which, in turn, trigger executioner caspases. Subsequently, the activated executioner caspases destroy the cells by breaking down proteins haphazardly.

Several studies have been conducted on apoptosis and their number has increased significantly since the beginning of the 1990s. Aside from the importance of apoptosis as a biological occurrence, it has been found that flawed apoptotic processes have been responsible for various diseases. In fact, too much of apoptosis usually leads to atrophy, while too less apoptosis may lead to unrestrained cell multiplication as in the case of cancer. A number of aspects such as caspases and Fas receptors actually encourage apoptosis. On the other hand, some members belonging to the Bcl-2 protein family slow down the process of cell destruction via apoptosis.

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German scientist Karl Vogt described the theory of apoptosis for the first time in 1842. Some years later, another German anatomist Walther Flemming presented a more accurately described process of apoptosis or programmed cell death. Nevertheless, the topic was revived only in 1965. While he was examining tissues employing electron microscopy at the University of Queensland, John Foxton Ross Kerr succeeded in differentiating apoptosis from necrosis or traumatic cell death.

After Kerr published a paper illustrating this biological phenomenon, he was invited to work with Alastair R Currie and Andrew Wyllie, who was a graduate student of Currie at the University of Aberdeen. In 1972, these three scientists published decisive article on apoptosis in the British Journal of Cancer. Initially, Kerr employed the phrase programmed cell necrosis. However, later in the article, he termed the process relating to cell death as apoptosis. In fact, these three scientists credited James Cormack, a Greek language professor at the University of Aberdeen, for proposing the word apoptosis. On March 14, 2000, Kerr was presented with the Paul Ehrlich and Ludwig Darmstaedter Prize for his contribution in describing the process of natural cell death or apoptosis. Kerr shared the honour with H. Robert Horvitz, a biologist based in Boston.

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Apoptosis involves several distinctive stages. In the first phase, the cell begins to change its shape and turns spherical owing to the activated enzymes consuming the proteins present in the cell. Subsequently, the DNA inside the cell nucleus begins to disintegrate and gradually shrink. At the same time, the membrane encircling the nucleus starts breaking down and eventually it does not remain the usual external layer of the cell.

Since the nuclei of the cells are not protected any longer, the DNA of the cells disintegrated into irregular fragments. Now, the cell's nucleus is split into several bodies each with irregular amounts of the DNA. On the other hand, the cell also undergoes a process known as blebbing, wherein the different parts of the cell starts breaking off. In the end, the cell is broken completely into various pieces and is engulfed by relatively smaller cells known as phagocytes.

In case the final stage of apoptosis which involves phagocytic digestion is not completed properly, there are chances of danger. The undigested pieces of a cell can amass inside the body. Studies undertaken on mouse neonates and mouse embryos have shown that they even result in death.

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Aside from this type of cell death, apoptosis may also take place owing to signals within the cell (known as intrinsic) or external signals (called extrinsic). When apoptosis is caused by intrinsic signals, it possibly may be owing to the absence of adequate nutrient supply to the cells or damage caused to the DNA inside the nucleus. On the other hand, extrinsic apoptosis may take place when there is a viral infection or in reaction to treatments such as chemotherapy. Occasionally, a cell sets off the process of self destruction with a view to combat specific viruses, such as HIV.

In present times, studies involving apoptosis have assumed great significance. In fact, most of our present perceptions regarding cell death are from the studies undertaken in the 1990s as well as the ongoing research on this subject. It is worth mentioning here that ability to set off cell death is wanted as well as advantageous. This is especially true when physicians try to destroy tumour tissues. Moreover, having a proper understanding of the manner in which the apoptosis process actually works helps scientists to undertake further studies on stem cells as well as their potential uses in medicine.

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