07.03.2014 change 07.03.2014

Leaking proteins can cause hypertension

Photo: Fotolia Photo: Fotolia

Mutation may cause certain proteins in the cell membrane to begin to leak and too much sodium getting into the cells. This can lead to hypertension. Polish doctoral student investigated the mechanisms of action of sodium-potassium pump.

Studies will help to better understand some of the mechanisms that lead to hypertension. Perhaps in the future the research will also help in the prevention and treatment of the disease.

Wojciech Kopeć, Polish doctoral student at the University of Southern Denmark in Odense with his team investigated the sodium-potassium pump, especially one of the proteins that form it. "It is present in all human cells. Its main task is to maintain an appropriate difference in the concentrations of sodium and potassium ions inside and outside the cell" - said Wojciech Kopeć in an interview with PAP. The task of the protein is to remove excess sodium from the cell and pump potassium in. The researcher explained that the protein is so common and necessary, it would seem that any mutation in the gene encoding this protein would result in cell death.

However, a few months ago, Danish researchers (a team at the University of Aarhus) found that such mutations are characteristic of adrenal tumours, and they may be linked to hypertension. This could apply to 5 percent hypertensives.

It was, however, unclear what happens in the cells of adrenal tumours and how mutations, which occur there, affect the functioning of cells. Wojciech Kopeć worked on computer simulations, which allowed to better understand these mechanisms. "We were able to confirm what the experiments suggested. As a result of these mutations, protein - which is located in the cell membrane - starts to leak" - said Kopeć. Water with sodium protons or ions travels through the diaphragm - which is the cell membrane - into the interior of the cell. This starts a cascade of events that can lead to hypertension.

Although the general principle of the sodium-potassium pump is known, it is not fully explored. "The pump at one time is capable of attaching sodium which is disposed outside the cell, then it binds with potassium. It is not known how the protein is able to show selectivity between sodium and potassium. We want to examine this" - said Kopeć.

The PhD student told about creating computer simulations of proteins functioning. Researchers obtained from crystallographic structure of the protein other teams. "This is like a frozen +photos+ of protein in a given state. However, in the cell everything is in motion and subject to fluctuations" - said Kopeć. He explained that purpose of the simulation is to introduce dynamics into the system and help to understand the phenomena which occur at this point. "When I received the file with the structure, I had to figure out how to simulate the function of the protein" - explained the researcher from Danish university. He developed a model membrane, fitted protein into it, added the appropriate conditions and checked, how the protein would behave. It turned out that the protein produced by the mutated gene was leaking water with ions into the cell.

The discovery of the mechanisms associated with defective protein was possible by using one of Denmark’s most powerful cluster computers Horseshoe 6, which belongs to the University of Southern Denmark.

PAP - Science and Scholarship in Poland, Ludwika Tomala

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