Nobel Prize in Medicine for the adaptation of cells to the availability of oxygen

2019/10/07 Galarraga Aiestaran, Ana - Elhuyar Zientzia Iturria: Elhuyar aldizkaria

• Sariak
• Medikuntza
• Anatomia/Fisiologia

Adaptation to the availability of oxygen is the basic mechanism of life. Therefore, the clarification of the keys to this mechanism has been fundamental to know cellular physiology, as well as to improve the understanding and development of treatments to combat certain diseases such as anemia and cancer. For all this, the Karolinska Institute has decided to give them the Nobel Prize in Physiology or Medicine this year.

The communication recalls the previous steps that led to this discovery. In fact, Otto Warburg received the Nobel Prize in 1931 for the enzymatic process by which cells obtain energy. In 1938 she was donated to Corneille Heyman for demonstrating how the body measures blood pressure and oxygen level and how she conveys that information to the brain.

XX. Since the beginning of the twentieth century it was known that one of the main mechanisms of response to hypoxia is the increase of the hormone EPO. This increases the production of red blood cells. However, they did not know how the oxygen level controls this mechanism.

And that's what Gregg Semenza analyzed. Specifically, he investigated the EPO gene and how the gene regulates the change in oxygen levels. For this purpose, he used genetically modified mice, identifying fragments of DNA near the EPO gene. Its activity depends on hypoxia.

Also Sir Peter Ratcliff investigated the regulation of the EPO gene in relation to oxygen, and the research groups of both observed that this mechanism is not only in the cells in which the EPO is generated, that is, in the kidneys. On the contrary, they showed that it is present in almost all tissues of the body.

In addition, Semenza identified the HIF complex. He found that the HIF complex is associated with previously identified DNA fragments, and discovered the genes that encode it. They knew better and better the molecular mechanism that is activated in hypoxia.

Complementary research of a hereditary disease

At the same time, William Kaelin was investigating a hereditary disease, von Hippel-Lindau (VHL). People with this mutation have a high risk of developing certain cancers.Kaeline showed that the protein encoding the VHL gene prevents the appearance of cancer and that those who had it mutated, in turn, had increased the expression of the genes regulating hypoxia. So he saw that the VHL had some influence on the response to hypoxia.

Finally, Rartcliff showed what this influence consists of. Thus, step by step, the molecular mechanism of how cells measure the level of oxygen and fit to its usefulness was clarified.

This mechanism is key to the functioning of the body, for example, during intense exercise, in the development of blood vessels and placenta of the fetus, and in the immune system. It also influences many diseases. For example, chronic renal patients often have severe anemia due to a shortage of EPO. In tumors, the oxygen-regulated mechanism is used for the creation of new blood vessels and the proliferation of cancer cells. Therefore, many researchers are studying how to influence this mechanism.