How is Cell Death Reversed?

Apoptosis (programmed cell death) has many different triggers. All these triggers activate the disintegrating proteins called caspase. Disrupting hundreds of different proteins, genomes, organelles, and cell skeletons within the cell; it causes the cell to shrink, disintegrate and die.
General dogma is that there is no recycling of apoptosis. Tang, a researcher at Hong Kong University, explored whether this was really the case. In his study, he exposed a large number of cancer cells to toxins, such as ethanol, and waited until apoptosis symptoms such as caspase activation and cell shrinkage appeared. In the next stage, instead of throwing dead cells at the end of the experiment, they washed them and kept them overnight with fresh medium.
Interestingly, some cells recovered their normal morphology when the cells were checked again in the morning. This event was called anastasis. Apoptosis means decline in Greek and this process facilitates the natural recycling of cells. Anastasis, on the other hand, means ascension. Scientists were initially skeptical that cells could return from death. Therefore, publications on this subject were rejected more than 11 times in the last three years. That's why Tang, who went to John Hopkins University, continued to do more research. He also studied human cancer cells, as well as mouse liver, rat heart, ferret brain, and human fibroblast (skin) cells. Although the cells were affected by DNA damage and cell disruption, they could be replaced after an advanced stage of apoptosis.
Since anastasis was officially named in 2012 , researchers have continued to explore how cells can be regenerated even after they have been severely damaged by apoptosis . Scientists have observed that in human cells, the fragmented mitochondria (the organelle that produces energy in the cell) has become complete again and that a group of mRNAs are produced and stored during apoptosis so that the cells can return to life. In addition, evidence for the presence of anastasis was also observed in the drosophilada (fruit fly).

How do the cells survive?

Cells; can live for days, months or even years. But when apoptosis begins, the cell goes to death quickly. Within 10 minutes after activation of caspases, the cell is visibly changed. During this process, the cell becomes smaller and the DNA fragmented. In addition, the phosphatidylin molecule, which is formed as a result of the caspase interacting with the cell membrane, is a signal for phagocytic cells (immune cells that digest other cells).
Apoptosis is triggered in a number of different ways; activates the enzymes named caspase, which break down the DNA, organelles and cell skeleton of the cell. Caspases also allow other cells to be digested so that residues of dead cells can be digested. However, if anastasis occurs in the late stages of apoptosis, surviving cells may carry serious DNA damage and other genetic damage may cause tumor formation.
In 2015, Ichim Tait and his colleagues, who worked with human cells that were reproduced in the laboratory, presented a concept different from the anastasis, which was called apoptosis. This concept refers to cells that are renewed after radical changes caused by apoptosis. Mitochondria were believed to be synchronous infiltrations in all other mitochondria in the cell when caspases began to leak out the potential triggering cytochrome c. But when the researchers checked this, they found that only a few mitochondria leaked. As a result, a small number of caspases are activated and the cells survive.
Apoptosis, which is similar to anastasis, involves the onset of apoptosis that does not result in death. However, this type of apoptosis cell enters apoptosis in part. In a successful apoptosis, much less than the caspase level is activated, and these few enzymes partially cleave the cell. On the other hand, according to Tang's findings, even when apoptosis is complete, cells can be repaired.
The researchers showed that, by time-lapse live cell microscopy, the HeLa cell fragments combined to form normal cell morphology . How the apoptosis begins is not important for the occurrence of anastasis. Anastasis; cold, protein hunger and toxic chemicals, such as damage caused by conditions can save the cell. Even in cells with advanced apoptosis, the fragmented mitochondria can unite and return to normal. A few hours after regeneration, the cells also eliminate the target of phagocytic cells by eliminating the phosphotythilserine molecule in its membranes.
In 2017, Montell and Tang independently published the molecular mechanism of anastasis. Montell's group found that more than 1,000 genes were activated in HeLa cells that had entered apoptosis. The molecular response of anastasis is similar to the response of surviving cells after autophagy (digestion of waste structures in the cell). In addition, mRNAs accumulated in the cell to recover the cell prior to apoptosis prepare the cell for anastasis. Tang et al. mouse liver cells; By eliminating the damaged mitochondria, the free radicals and other cellular components observed that the activity of the genes involved changed.

Effects of Apoptosis Return

One possible function of anastasis is to prevent permanent damage to a temporary condition. For example, in a developing organism, growth factor deficiency may occur randomly at intervals and this may trigger apoptosis during the rapid growth of cells. Montell et al. Found that the cells survived after caspase activation in the larval brain and anastasis could be seen during Drosophila development.
Anastasis may also promote evolutionary changes. In the study of Tang, anastasis was observed in Drosophila reproductive cells in the presence of environmental stress conditions such as hunger and cold shock. This indicates that cells can undergo mutations that will pass through new generations during apoptosis.
Anastasis can serve more purposes than simple protection. In 2012, Tang and Montell observed that genomic errors were seen when genetic damage was repaired in cells that survived apoptosis. As a result, a percentage of surviving cells has chromosomal abnormalities and other genetic disorders cause tumor growth. The cell is now on the brink of continuous death; Damage to the tissues (for example, continuous consumption of hot beverages as a result of esophageal cancer and chronic alcohol use as a result of liver cancer) can explain the risk of developing a high rate of cancer. Even in the case of failed apoptosis (the damage is less serious before healing), the genome is sometimes unstable and even some cells become tumor cells.
The ability of the cell to return to programmed cell death; Some cancers can play a role in getting rid of therapeutic approaches. Radiation and commonly used chemotherapy drugs stimulate apoptosis and kill many tumor cells, while surviving cells cause recurrence of cancer. Moreover, cancer cells surviving such therapies may be more resistant to drugs by developing new mutations.
Tang and colleagues also found that anastasis could activate genes related to angiogenesis and cell migration in Drosophila. Angiogenesis also helps the cells to get rid of apoptosis by increasing the absorption of nutrients and helping to remove the waste. In addition, these changes increase the spread of cancer cells.
The discovery of the potential link between cancer and anastasis may be a new treatment to suppress anastasia in a cancer cell that has died during and after cancer treatment, and to prevent recurrence of cancer. Targeting anastasis may also be used in the treatment of diseases caused by loss of non-renewable cells, such as heart muscle cells and neurons. A better understanding of anastatasis does not only give information about how cells are saved from disease and damage, but also allows scientists to better understand cell death.
Source: poxox blogs
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