25 April 2019

Cancel apoptosis

An enzyme has been discovered that can stop cell death

Vladimir Guillen, Naked Science

Defective cells (i.e. infected or mechanically damaged) are destroyed in the process of apoptosis – regulated cell death. Thanks to this, the cells are constantly updated. In the body of a healthy person, up to 70 billion cells are destroyed during apoptosis. If the process changes – accelerates or slows down – it leads to oncological, autoimmune, neurodegenerative and other diseases.

There are several enzymes called apoptotic endonucleases involved in programmed cell death. Biochemists of the RUDN (Peoples' Friendship University of Russia) have demonstrated that one of them – EndoG – can stop the process of cell death if it gets out of control. It turned out that increased EndoG secretion lowers the volume of another endonuclease called deoxyribonuclease I (DNase I) and slows down the process of apoptosis at an early stage. The two enzymes must initially work together, that is, simultaneously act on the DNA of the defective cell to destroy it. Biochemists from the RUDN were the first to demonstrate that EndoG and DNase I are, in fact, rivals rather than comrades. The results of the study are published in the journal Biochimie.

"The EndoG enzyme works as a defense mechanism against DNase I and DNA destruction. In this case, the mechanism of cell death turns out to be very interesting: EndoG, a DNA–destroying enzyme, can stop apoptosis if it proceeds very quickly or goes too far," says Dmitry Zhdanov, co-author of the study and candidate of Biological Sciences from RUDN.

To conduct an experimental study, scientists from the RUDN used the blood of 50 people from 18 to 25 years old without diagnosed diseases. The researchers provoked an increase in EndoG synthesis in donor T-lymphocytes. Then, using a DNA-destroying substance called bleomycin, the apoptosis process was started in the cells and the levels of EndoG and DNase I were measured. It turned out that an excess of EndoG lowers the level of DNase I, which means that it slows down the entire process of apoptosis.

"We were the first to demonstrate a negative relationship between EndoG and DNase I. This discovery can help regulate the cell's response to any damage, and the activation of EndoG can become a protective mechanism against uncontrolled cell death," adds Zhdanov.

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