Cells’ Suicide Upon A Signal

Genetically controllable self-destruction of cells or apoptosis (originating from the Greek “apoptosis” – defoliation) – is one of important processes in animate nature. Surprising transformations of embryos as they grow, development and disappearance of organs and tissues – all these are apoptosis’ work. It can protect from disease or cancer or it can mutilate and kill, for example, in case of infarct or autoimmune diseases when a lot of cells perish at once.

Biochemists from the Scientific Research Institute of Physicochemical Biology (Lomonosov Moscow State University) jointly with their British colleagues have discovered that apoptosis in one cell entails the death of neighboring cells as if they came to an agreement. The researchers have assumed that the signal for mass suicide of cells is sent by hydrogen peroxide, which is formed in mitochondria of apoptosis cells, gets into the environment, easily penetrates via membranes inside healthy cells, and healthy cells in response to the invasion also start their dissociation. This is the way young frog’s tail “dissolves”.

To investigate the mechanism of this phenomenon, the researchers observed the process by the example of the cancer cells culture (uterus carcinoma) growing in Petri dishes in a thin layer. The researchers processed individual cells and groups of cells by a hormone – tumor necrosis factor. Further developments were observed by the researchers via a microscope and camera-recorded.

Apoptosis started in the test uterus carcinoma cells, and they perished soon. However, surrounding cells also decayed simultaneously, although tumor necrosis factor could affect them by no means. This means that the dying cells produce some chemical signal for neighbors’ self-destruction. This property of apoptosis cells allows, for example, the plants to fight viral infections, when the affected section is isolated from healthy ones by a layer of a dead tissue, as apoptosis spreads quicker than infection. The researchers have discovered that the death from apoptosis is very “contagious”, as it is not necessary for the cells deciding to suicide in the company of apoptosis specimen to be contiguous to them or to have slit contacts for exchange of substance with them, it is sufficient simply to grow in the same culture broth.

The biologists have assumed that this signal is hydrogen peroxide, which is formed in cells’ mitochondria. This substance is relatively stable and can move rather far in intercellular space. To verify that, the researchers placed into nutrient medium the catalase enzyme that transforms peroxide into water. As a result, the intercellular “transmitter” ceased operation. In other experiments, specific antioxidant was introduced into apoptosis cells, the antioxidant gets accumulated in mitochondria and prevents peroxide from being formed in them. The effect was the same. Consequently, it is hydrogen peroxide from the cells dying according to the apoptosis principle that gets into the environment and makes other cells act in the same way.

A healthy organism maintains equilibrium between the death of old cells and appearance of new cells. Apoptosis is a genetically controllable process, which relieves the organism from impaired, unnecessary or defective cells. About five percent of human organism’s cells per day undergo apoptosis, and they are replaced by new ones. In the course of apoptosis, rounded bodies are formed from the cell, the bodies being surrounded by a membrane (“apoptosis corpuscles”), which are immediately consumed by surrounding cells. As a result, the cell disappears within several dozens of minutes. In case of apoptosis decrease, cell accumulation happens, including accumulation of cancerous cells, but apoptosis increase may cause tissue atrophy, therefore, the researchers aim at learning to control the process. The specialists believe that apoptosis is one of components of ageing and phenoptosis, programmed organism death. Probably, the new generation of drugs delaying ageing (geroprotectors) will be based on antioxidants aimed particularly at mitochondria.