Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Fat overload kills mammalian cells — key culprit identified

20.01.2006


Investigating the harmful health effects of excess fat, researchers at Washington University School of Medicine in St. Louis have identified a protein that triggers death in mammalian cells overloaded with saturated fat.


The internal "skeleton" (in red) of cells is altered by exposure to high fat.



When the researchers halted production of this protein, called EF1A-1, the cells were able to thrive in ordinarily damaging amounts of the saturated fat palmitate, a fat abundant in Western diets. At the same concentration of palmitate, normal cells still producing EF1A-1 rapidly died. The study will be published in the February 2006 issue of Molecular Biology of the Cell.

"When lipids (fats) accumulate in tissues other than adipose tissue, cellular dysfunction or cell death results," says senior author Jean Schaffer, M.D., associate professor of medicine and of molecular biology and pharmacology. "For example, preliminary studies on animals suggest that the accumulation of fat in the pancreas contributes to the development of diabetes, and accumulation of lipids in skeletal muscle of leads to insulin resistance."


Other studies have linked the genesis of heart failure to fat-induced cell dysfunction and cell death in the heart. "As physicians our primary focus in diabetic patients is on glucose control," says Schaffer, a member of the Center for Cardiovascular Research at the School of Medicine and a cardiologist at Barnes-Jewish Hospital. "But it appears we should also be more aggressive with respect to lowering lipids such as triglycerides and fatty acids."

With the discovery of EF1A-1’s role, this study is the first to identify a critical step in the pathway that leads from high cellular fat to cell death, according to Schaffer. EF1A-1 is an extremely abundant protein with several diverse functions within cells, including protein synthesis and maintenance of the cytoskeleton, the cell’s internal support structure.

In mammalian cells grown in culture, the researchers saw that EF1A-1 and the fat palmitate work hand in hand: the presence of EF1A-1 dictated sensitivity to palmitate-induced cell death, and palmitate caused a rapid increase of the amount of EF1A-1 produced.

Schaffer’s laboratory earlier had developed a transgenic mouse that accumulates fat in its heart muscle cells resulting in the death of cells, heart failure and premature death. They found that EF1A-1 was increased nearly three-fold in the hearts of these animals.

Removal of EF1A-1 protected cells from palmitate-induced death, and its absence allowed cells to withstand assault by highly reactive oxygen molecules. According to study authors, this indicates that EF1A-1 probably contributes to cell death from oxidative stress, which is known to stem from high lipid levels. Cytoskeletal changes seen in cells missing EF1A-1 suggested to the researchers that EF1A-1’s cytoskeletal role also is important in cell death resulting from fat overload.

"Cells have a lot of mechanisms for incorporating fatty acids into storage forms, for metabolizing them or for using them in cellular membranes," Schaffer says. "But saturated fats like palmitate are poorly stored in the tiny fat droplets normally found in most cells and therefore are more likely to enter into pathways that lead to cell death such as the one in which EF1A-1 is involved."

In the process of identifying the role of EF1A-1, the lab members uncovered other proteins implicated in the toxicity of excess fats. They are now investigating each to find out what part it plays.

Future investigations by Schaffer’s research team will study the EF1A-1 protein to see whether fatty molecules directly alter the protein, or if they cause it to relocate within the cell.

Borradaile NM, Buhman KK, Listenberger LL, Magee CJ, Morimoto ETA, Ory DS, Schaffer JE. A critical role for eukaryotic elongation factor 1A-1 in lipotoxic cell death. Molecular Biology of the Cell, February 2006.

Funding from the National Institutes of Health, the Washington University School of Medicine--Pharmacia Biomedical Program (JES) and the Heart and Stroke Foundation of Canada supported this research.

Washington University School of Medicine’s full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked third in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.

Gwen Ericson | EurekAlert!
Further information:
http://www.wustl.edu
http://mednews.wustl.edu/news/page/normal/6398.html?emailID=7817

More articles from Life Sciences:

nachricht Embryonic development: How do limbs develop from cells?
18.05.2018 | Humboldt-Universität zu Berlin

nachricht Reading histone modifications, an oncoprotein is modified in return
18.05.2018 | American Society for Biochemistry and Molecular Biology

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Explanation for puzzling quantum oscillations has been found

So-called quantum many-body scars allow quantum systems to stay out of equilibrium much longer, explaining experiment | Study published in Nature Physics

Recently, researchers from Harvard and MIT succeeded in trapping a record 53 atoms and individually controlling their quantum state, realizing what is called a...

Im Focus: Dozens of binaries from Milky Way's globular clusters could be detectable by LISA

Next-generation gravitational wave detector in space will complement LIGO on Earth

The historic first detection of gravitational waves from colliding black holes far outside our galaxy opened a new window to understanding the universe. A...

Im Focus: Entangled atoms shine in unison

A team led by Austrian experimental physicist Rainer Blatt has succeeded in characterizing the quantum entanglement of two spatially separated atoms by observing their light emission. This fundamental demonstration could lead to the development of highly sensitive optical gradiometers for the precise measurement of the gravitational field or the earth's magnetic field.

The age of quantum technology has long been heralded. Decades of research into the quantum world have led to the development of methods that make it possible...

Im Focus: Computer-Designed Customized Regenerative Heart Valves

Cardiovascular tissue engineering aims to treat heart disease with prostheses that grow and regenerate. Now, researchers from the University of Zurich, the Technical University Eindhoven and the Charité Berlin have successfully implanted regenerative heart valves, designed with the aid of computer simulations, into sheep for the first time.

Producing living tissue or organs based on human cells is one of the main research fields in regenerative medicine. Tissue engineering, which involves growing...

Im Focus: Light-induced superconductivity under high pressure

A team of scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg investigated optically-induced superconductivity in the alkali-doped fulleride K3C60under high external pressures. This study allowed, on one hand, to uniquely assess the nature of the transient state as a superconducting phase. In addition, it unveiled the possibility to induce superconductivity in K3C60 at temperatures far above the -170 degrees Celsius hypothesized previously, and rather all the way to room temperature. The paper by Cantaluppi et al has been published in Nature Physics.

Unlike ordinary metals, superconductors have the unique capability of transporting electrical currents without any loss. Nowadays, their technological...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Save the date: Forum European Neuroscience – 07-11 July 2018 in Berlin, Germany

02.05.2018 | Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

 
Latest News

Supersonic waves may help electronics beat the heat

18.05.2018 | Power and Electrical Engineering

Keeping a Close Eye on Ice Loss

18.05.2018 | Information Technology

CrowdWater: An App for Flood Research

18.05.2018 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>