Translartion. Region: Russians Fedetion –
Source: Novosibirsk State University – Novosibirsk State University –
Scientists from the Laboratory of Optics and Dynamics of Biological Systems Physics Department of NSU and the Department of Organic Chemistry Faculty of Natural Sciences of NSU created a new photosensitive molecule, the breakdown of which under the influence of ultraviolet radiation releases adrenaline without the formation of the oxidized form (adrenochrome), which has a neuro- and cardiotoxic effect. It was used to influence platelet receptors with light. It turned out that the release of adrenaline significantly increases the activation of platelets.
The results of the study were published in January of this year on the website of the Journal of Xenobiotics (Reducing the Formation of Toxic Byproducts During the Photochemical Release of Epinephrine). The article is available at the link: HTTPS: //d.org/10.3390/eh15010008. The study was supported by the grant of the Russian Science Foundation No. 23-75-10049 and is being conducted within the framework of the project “Study of platelet activation under the influence of combined stimuli using optically-mediated release of ligands”.
-The idea of managing living cells with the help of light is very attractive for researchers, because it can be accurately focused on a particular area, turn on at a given moment and influence any photosensitive receptor. The only problem is that not all living cells have such receptors. They are just platelets. We needed to “force” them to feel light through any signal molecules. The fact is that almost all cells have receptors sensitive to some substances. Different cells feel different signal molecules, and one of the ways is to make artificial compounds that absorb light, and after that they can, decaying into the components or in any way by rebuilding their structure, join the receptors. Then, after the exposure of the light, the cell will begin to “feel” them. This is how it is possible to “force” the cell to show sensitivity to light. Scientists began to develop and apply various compounds of this action to various cells for a long time – from the second half of the last century. Within the framework of our laboratory, this activity has also been conducted over the past years. Our chemical colleagues from the laboratory of photo activated processes of the SB RAS are engaged in the synthesis of molecules, but we study their properties and use to study various cells, mainly platelets, ”explained Alexander Moskalensky, head of the optics and dynamics of the FF NSU Biological Systems.
Classic photosensitive adrenaline analogues developed in the 90s of the last century, when exposed to light, release adrenaline, which in the process of oxidation is converted into adrenochrome, which is toxic to living cells. For this reason, it is undesirable to use it as an activator of sensitivity to light in living cells, since this substance can trigger other undesirable processes in them or even kill them. Therefore, scientists were faced with the task of finding a way to reduce the formation of adrenochrome, but without stopping the release of adrenaline. As a result, it turned out that this problem can be solved by a simple modification of the molecule, namely, the introduction of a carbamate bridge of 4 carbon and oxygen atoms. The release of adrenaline in this case continued as before, and the amount of its transition to the oxidized form was significantly reduced.
— We compared two lines of molecules — classical and modified. Surprisingly, while the classical compound resulted in the formation of adrenochrome, its analog with a carbamate bridge did not cause this by-product, which resulted in a pure release of the active substance, i.e. adrenaline. The exposure of both compounds to light was carried out under identical conditions, then the products obtained by photolysis were analyzed using ultraviolet spectroscopy, chromatography and nuclear magnetic resonance. Subsequently, we evaluated the new compound using an in vitro platelet activation assay. The results showed that the release of adrenaline significantly enhances platelet activation, which makes it a valuable tool for in-depth studies of cellular signaling, — said Alexander Moskalensky.
Since UV radiation does not penetrate the body, it is not possible to use modified molecules of the photosensitive adrenaline analogue inside the body. Therefore, scientists plan to use them to study platelet activation in a test tube, namely, in blood samples. With their help, it will be possible to develop new analysis methods and obtain new information about the platelet activation process.
This method will allow researchers to obtain more accurate data on the effect of adrenaline on platelet activation. This is important because platelets are very sensitive to mechanical impacts, fluid flows, and other types of impact that can affect the results of such studies.
Currently, the laboratory’s scientists are developing the next molecule – a photosensitive analogue of adrenaline based on the dye BODIPY, which will be activated by light in the green region of the spectrum, and they also have an understanding of how to modify molecules that could be activated in the red region of the spectrum.
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