Oxidative stress: revaluation of values
Sensational conclusions of German scientists:
the role of oxidative stress in the development of diseases should be reviewed
LifeSciencesToday based on DKFZ materials: Preventive Detention for Oxidizing AgentsIt is commonly believed that oxidative stress causes a number of diseases.
Until now, the usual practice of assessing oxidative stress levels has been to determine the degree of oxidation of the glutathione molecule in cell extracts. Scientists of the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have found that in stressed cells, oxidized glutathione is stored in a storage for biochemical waste. This protects cells from oxidative stress... and calls into question the validity of the traditional assessment method and the reliability of the data obtained on its basis.
Cancer, Alzheimer's disease, atherosclerosis – the list of diseases associated by scientists with oxidative stress can be continued. It also includes the aging process. Oxidative stress is caused by the so-called active (or reactive) forms of oxygen (ROS), which include the notorious free radicals. If a cell is exposed to chemically active oxygen compounds, the amount of which is greater than it can instantly destroy, it is in a state of oxidative stress. As a result, its important components, such as proteins, DNA and lipids, are oxidized and, consequently, damaged.
To determine whether a cell is in a state of oxidative stress, scientists often analyze the degree of oxidation of glutathione. Theoretically, the amount of oxidized glutathione should indicate whether the cell is healthy or in a state of oxidative stress. But a group of scientists led by associate professor Dr. Tobias Dick proved that this assumption, on which the conclusions of a large number of scientific studies are based, is absolutely untenable.
"Until now, to measure the amount of oxidized glutathione, the cell had to be destroyed," explains Dr. Dick. "However, this means the loss of its spatial structure."
Thus, practically nothing was known about where the oxidized glutathione is in the cells. Scientists assumed that it remains in the cytoplasm, where it is formed.
To find out the actual location of oxidized glutathione, Dr. Dick and his colleagues developed biosensors – genetically encoded fluorescent sensors– that show oxidized glutathione in intact cells by light signals. In yeast experiments, researchers tracked the path of oxidized glutathione in a living cell in real time for the first time. They were surprised to find that, instead of remaining in the cytoplasm, it immediately locks itself in a safe depot – vacuoles.
The biosensor tracks oxidized glutathione in the vacuoles of yeast cells.
(Photo: © Tobias Dick, German Cancer Research Center)
This means that the cytoplasm, in which many important metabolic processes take place, is reliably protected from oxidative damage. The cytoplasm of cells that, using the traditional method of evaluating oxidized glutathione, would be considered to be in a state of oxidative stress, turned out to be completely healthy. Later, Dr. Dick and his colleagues showed that this is true not only for yeast, but also for various cells of higher organisms, in particular, mammals, as well as for cancer cells.
These results mean that the level of oxidized glutathione is not an indicator of the oxidative stress experienced by the cell.
"Thus, it is important to overestimate the results of previous studies in which the link between oxidative stress and various diseases was established by the traditional method," says Dr. Dick.
Article by Bruce Morgan et al. Multiple glutathione disulfide removal pathways mediate cytosolic redox homeostasis is published in the journal Nature Chemical Biology.
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