A group of researchers from the Lomonosov Moscow State University in collaboration with their Irish colleagues from the University College Cork has studied the early response of cells to ischemia, which is a restriction in blood supply to tissues causing the death of the cell. The article describing the results of their studies is published in Genome Biology. It’s impact factor is 10.5.

Dmitry Andreev, PhD, senior research fellow at the A.N. Belozersky Institute Of Physico-Chemical Biology and Ivan Shatsky, PhD, professor at the same institute, described the results.

“The study became possible due to the development of techniques Next-Generation Sequencing (NGS), which made a real revolution in the life sciences. In particular, we used the ribosome profiling technique which allows the capture of a “snapshot” of all protein synthesis in the cell at a given time. The protein synthesis in the cell is driven by ribosomes, which are huge macromolecular machines capable of reading the information encoded in the messenger RNA and synthetizing corresponding proteins. At any time thousands of various proteins, are being synthesized by ribosomes. When a change in external conditions occurs, ribosomes can quickly switch to the other messenger RNA and begin to synthesize the proteins necessary for adaptation to new conditions.

“We decided to use this method to study the changes in gene expression in the cells upon oxygen and glucose deprivation, - Dmitry Andreev explains, - “This is a model for studying ischemia”.

Prolonged exposure to ischemia always leads to irreversible tissue damage, and as a consequence to the cell death. However, within a short time after the stress cells are still viable, what means they can rescued and thereby prevent the devastating effects of ischemia. That is why understanding of the processes occurring in a cell in the early hours, or even minutes after ischemia, can have a very important fundamental and practical significance.

We have studied the early response to ischemia in the first hour after stress. It appeared that within 20 minutes after the stress significant changes in the synthesis of proteins occur. It is interesting that the most significant changes occur in the synthesis of proteins involved in mitochondrial respiratory chain. Apparently, the cell tries dramatically to adapt to new conditions and to switch to “alternative” energy sources in order to avoid death.

The HIF signaling cascade is also important because its activity is necessary for the survival of a variety of tumors as many cancer cells face with chronic shortage of oxygen due to defects in the blood supply, and in order to survive they have to adapt to the conditions of hypoxia. Therefore HIF is a very promising target for cancer therapy.

As a indication of the scientific interest in this family, there are more than 12,000 scientific studies on the subject, since it was first identified in 1995.

“We have many plans how to develop this subject, but at the moment we prefer not to share them as in this area of research there is a very serious competition, including scientists from the world’s leading research centers. It is necessary to note that a very large contribution of all members of the team took place in this work and we look forward to continuing the collaboration with our colleagues”, - Dmitry Andreev summed.

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Vladimir Koryagin
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Lomonosov Moscow State University