Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Protein Controls Acid in Cells by Direct Detection of Volume Changes

06.07.2004


A protein responsible for regulating acid levels within cells – and pumping out acid accumulated in cardiac cells after a heart attack – activates in direct response to changes in a cell’s volume, according to a new study by researchers at UT Southwestern Medical Center at Dallas.

Their findings show that the protein NHE1, which is found in the membranes of nearly all cells and is especially active in cancer cells, is regulated by the stretch and pull of the membrane as a cell changes volume. The study appears in the Proceedings of the National Academy of Sciences and is available online.

NHE1, which is called a transporter protein, oscillates its shape rapidly in a cell’s membrane. This allows sodium from the outside to come in and protons – positively charged particles – from inside the cell to escape and lower the cell’s acidity. The fewer protons in a cell, the less acidic it is.



“The acidity in the cell is a huge signal for the cell,” said Dr. Donald Hilgemann, professor of physiology at UT Southwestern and senior author of the study. “The control of acidity regulates cell growth and proliferation.”

Hormones and many other signals that control cell growth and proliferation act on NHE1, he said.

“Our study shows that as cell volume increases, this transporter turns off. If volume decreases, it turns on by directly sensing mechanical changes in the membrane,” continued Dr. Hilgemann.

The NHE1 transporter is a protein of much interest to drug developers investigating ways to prevent cell death, which often accompanies heart attacks and strokes. In ischemia, where the blood supply is cut off to cardiac cells or brain cells, cells become very acidic. As the body’s normal metabolism gets going again, the NHE1 system starts pumping out the accumulated acid, exchanging the acid for sodium.

“It’s such an active system that you can overload the cell with sodium,” Dr. Hilgemann said. “Too much sodium is a major mechanism of cell death in ischemic episodes. Virtually every study that has been done (on inhibiting NHE1) has shown that if you block this transporter, you can prevent this type of cell death from ischemia.”

Previous studies have suggested that NHE1 plays a role in cancer cells that are trying to spread, or metastasize, to different parts of the body. As cancer cells move, they must change their volume, protruding at one end and retracting on the other. Dr. Hilgemann said other researchers speculate that NHE1 is at the head of the cell as it is moving, and is always rearranging itself to be at the cell’s head.

“While the cancer applications are very speculative, understanding this system can be very important for many aspects of cell biology,” he said.

The new study also compares NHE1 to another, very similar transporter called NHE3, which is found only in the kidneys.

“We found there are very specific differences in the way these two systems respond to changes in the cell,” Dr. Hilgemann said. “For example, the one in the kidney is involved in reabsorbing sodium, but it is not regulated at all by changes in cell volume.”

Dr. Hilgemann and his colleagues improved upon an existing experimental technique in order to study the NHE transporters and how acidity changes within a cell. The existing method involves skewering a single cell on a tiny, hollow needle called a pipette. Dr. Hilgemann’s group made their pipette larger to make a larger hole in the cell, which allowed them better control over what was inside and outside of the cell.

They also optimized the use of tiny sensors that can measure exactly the movement of protons across the cell membrane. “This tells us how the acidity is changing,” Dr. Hilgemann said. “Our advancements allow us to better show and study how these systems are working.”

Other UT Southwestern researchers who contributed to the study are Dr. Daniel Fuster, a postdoctoral researcher in internal medicine, and Dr. Orson Moe, director of the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research.

The research was funded by the National Institutes of Health and the Department of Veterans Affairs Research Service.

| newswise
Further information:
http://www.utsouthwestern.edu

More articles from Life Sciences:

nachricht Lab-free infection test could eliminate guesswork for doctors
26.02.2020 | University of Southampton

nachricht MOF co-catalyst allows selectivity of branched aldehydes of up to 90%
26.02.2020 | National Centre of Competence in Research (NCCR) MARVEL

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: High-pressure scientists in Bayreuth discover promising material for information technology

Researchers at the University of Bayreuth have discovered an unusual material: When cooled down to two degrees Celsius, its crystal structure and electronic properties change abruptly and significantly. In this new state, the distances between iron atoms can be tailored with the help of light beams. This opens up intriguing possibilities for application in the field of information technology. The scientists have presented their discovery in the journal "Angewandte Chemie - International Edition". The new findings are the result of close cooperation with partnering facilities in Augsburg, Dresden, Hamburg, and Moscow.

The material is an unusual form of iron oxide with the formula Fe₅O₆. The researchers produced it at a pressure of 15 gigapascals in a high-pressure laboratory...

Im Focus: From China to the South Pole: Joining forces to solve the neutrino mass puzzle

Study by Mainz physicists indicates that the next generation of neutrino experiments may well find the answer to one of the most pressing issues in neutrino physics

Among the most exciting challenges in modern physics is the identification of the neutrino mass ordering. Physicists from the Cluster of Excellence PRISMA+ at...

Im Focus: Therapies without drugs

Fraunhofer researchers are investigating the potential of microimplants to stimulate nerve cells and treat chronic conditions like asthma, diabetes, or Parkinson’s disease. Find out what makes this form of treatment so appealing and which challenges the researchers still have to master.

A study by the Robert Koch Institute has found that one in four women will suffer from weak bladders at some point in their lives. Treatments of this condition...

Im Focus: A step towards controlling spin-dependent petahertz electronics by material defects

The operational speed of semiconductors in various electronic and optoelectronic devices is limited to several gigahertz (a billion oscillations per second). This constrains the upper limit of the operational speed of computing. Now researchers from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg, Germany, and the Indian Institute of Technology in Bombay have explained how these processes can be sped up through the use of light waves and defected solid materials.

Light waves perform several hundred trillion oscillations per second. Hence, it is natural to envision employing light oscillations to drive the electronic...

Im Focus: Freiburg researcher investigate the origins of surface texture

Most natural and artificial surfaces are rough: metals and even glasses that appear smooth to the naked eye can look like jagged mountain ranges under the microscope. There is currently no uniform theory about the origin of this roughness despite it being observed on all scales, from the atomic to the tectonic. Scientists suspect that the rough surface is formed by irreversible plastic deformation that occurs in many processes of mechanical machining of components such as milling.

Prof. Dr. Lars Pastewka from the Simulation group at the Department of Microsystems Engineering at the University of Freiburg and his team have simulated such...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

70th Lindau Nobel Laureate Meeting: Around 70 Laureates set to meet with young scientists from approx. 100 countries

12.02.2020 | Event News

11th Advanced Battery Power Conference, March 24-25, 2020 in Münster/Germany

16.01.2020 | Event News

Laser Colloquium Hydrogen LKH2: fast and reliable fuel cell manufacturing

15.01.2020 | Event News

 
Latest News

Lights, camera, action... the super-fast world of droplet dynamics

26.02.2020 | Power and Electrical Engineering

Lab-free infection test could eliminate guesswork for doctors

26.02.2020 | Life Sciences

Scientists develop algorithm for researching evolution of species with WGD

26.02.2020 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>