Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers describe first functioning 'lipidome' of mouse macrophage

02.12.2010
For the first time, scientists have described not only the identities and quantities of fat species in a living mammalian cell – in this case, a mouse macrophage or white blood cell – but they also report how these lipids react and change over time to a bacterial stimulus triggering the cell's immune response.

Writing in the December 17 issue of the Journal of Biological Chemistry, lead author Edward A. Dennis, PhD, distinguished professor of pharmacology, chemistry and biochemistry at the University of California San Diego School of Medicine, said the work culminates more than seven years of effort by scientists in LIPID MAPS, a national consortium of 12 research laboratories at nine "core" universities, medical research institutes and life sciences companies collaborating to study the structure and function of lipids. UC San Diego serves as lead institution and information clearinghouse. Dennis is principal investigator.

"This paper is the essence of what we originally proposed," said Dennis. "This is our big, initial study, though we've published many other papers and have more in the pipeline." All nine core facilities in LIPID MAPS participated in the study.

Until relatively recently, lipid research has not received the same degree of attention as, say, genes or proteins. But fats are indisputably crucial to cell operations and overall health. Lipids represent major structural and metabolic components of cells and perform essential functions, such as membrane construction, energy production and intracellular communications.

"They're also a key in virtually all diseases," said Dennis. "Any condition involving inflammation involves lipids. It's hard to think of a disease, including cancer, in which lipids don't play some role."

Likewise for the subject of the research: the mouse macrophage.

"It would have been simpler to do this with yeast or bacteria," said Dennis, "but the macrophage is found in every kind of mammalian tissue (under different names). It's a major player in the immune system."

Moreover, scientists were able to study natural macrophages obtained from a live, well-established mouse model, rather than relying upon cultured cells. The model could also be genetically modified to test various hypotheses.

Previous studies have produced increasingly expansive and detailed "parts lists" of lipids. In October, for example, Dennis and colleagues published a paper that identified and quantified almost 600 distinct fat species circulating in human blood.

The new paper goes further. It chronicles the activity of more than 400 fat species in a macrophage after exposure to an endotoxin – a molecule found on the surfaces of bacteria that is recognized by macrophages and which triggers the cell's infection-fighting functions.

Each hour for 24 consecutive hours, scientists measured minuscule increases or decreases of targeted lipids, an indication of greater or lesser activity.

"The result is a temporal model of infection at the level of a single cell," said Dennis.

Similar experiments were conducted with macrophages exposed to a statin (a popular class of cholesterol-lowering drugs) and with macrophages simultaneously exposed to both an endotoxin and a statin.

"We chose to use a statin because we know it blocks production of cholesterol (a type of lipid), but statins also produce some anti-inflammatory effects. We wanted to see what else happens. And in fact, we saw some unexpected changes in certain metabolites."

Metabolites are the players and products of metabolism – the set of chemical reactions in cells that produce and sustain life.

Dennis said the findings lay the foundation for on-going and future projects to eventually produce a human "lipidome," a complete inventory of all fat species in the human body and how they work together.

"We only have three more years of the LIPID MAPS project," Dennis said. "But this is really just the beginning."

Co-authors of the paper are Raymond A. Deems of the Department of Chemistry and Biochemistry at UC San Diego; Richard Harkewicz of Department of Pharmacology, UC San Diego School of Medicine; Oswald Quehenberger and Gary Hardiman of UCSD's Department of Medicine, School of Medicine; H. Alex Brown, Stephen B. Milne and David S. Myers of the Department of Pharmacology, Vanderbilt University School of Medicine; Christopher K. Glass of the UCSD's Department of Medicine and Department of Cellular and Molecular Medicine, School of Medicine; Donna Reichart of UCSD's Department of Cellular and Molecular Medicine, School of Medicine; Alfred H. Merrill, Jr., M. Cameron Sullards and Elaine Wang of the Schools of Biology, Chemistry and Biochemistry and the Petit Institute of Bioengineering and Bioscience at Georgia Institute of Technology; Robert C. Murphy of the Department of Pharmacology, University of Colorado Denver; Christian R.H. Raetz, Teresa Garrett, Ziqiang Guan and Andrea C. Ryan of Department of Biochemistry, Duke University Medical Center; David W. Russell, Jeffrey G. McDonald and Bonne M. Thompson of Department of Molecular Genetics, University of Texas Southwestern Medical Center; Walter A. Shaw of Avanti Polar Lipids, Inc; Manish Sud, Yihua Zhao, Shakti Gupta, Mano R. Maurya and Eoin Fahy of the San Diego Supercomputer Center and Shankar Subramaniam of Department of Chemistry and Biochemistry, the Department of Cellular and Molecular Medicine and the San Diego Supercomputer Center, all at UC San Diego.

Funding for this project was provided by the National Institute of General Medical Sciences' Large Scale Collaborative "Glue" grant.

Scott LaFee | EurekAlert!
Further information:
http://www.ucsd.edu

More articles from Life Sciences:

nachricht The irresistible fragrance of dying vinegar flies
16.08.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How protein islands form
15.08.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Exotic quantum states made from light: Physicists create optical “wells” for a super-photon

Physicists at the University of Bonn have managed to create optical hollows and more complex patterns into which the light of a Bose-Einstein condensate flows. The creation of such highly low-loss structures for light is a prerequisite for complex light circuits, such as for quantum information processing for a new generation of computers. The researchers are now presenting their results in the journal Nature Photonics.

Light particles (photons) occur as tiny, indivisible portions. Many thousands of these light portions can be merged to form a single super-photon if they are...

Im Focus: Circular RNA linked to brain function

For the first time, scientists have shown that circular RNA is linked to brain function. When a RNA molecule called Cdr1as was deleted from the genome of mice, the animals had problems filtering out unnecessary information – like patients suffering from neuropsychiatric disorders.

While hundreds of circular RNAs (circRNAs) are abundant in mammalian brains, one big question has remained unanswered: What are they actually good for? In the...

Im Focus: RAVAN CubeSat measures Earth's outgoing energy

An experimental small satellite has successfully collected and delivered data on a key measurement for predicting changes in Earth's climate.

The Radiometer Assessment using Vertically Aligned Nanotubes (RAVAN) CubeSat was launched into low-Earth orbit on Nov. 11, 2016, in order to test new...

Im Focus: Scientists shine new light on the “other high temperature superconductor”

A study led by scientists of the Max Planck Institute for the Structure and Dynamics of Matter (MPSD) at the Center for Free-Electron Laser Science in Hamburg presents evidence of the coexistence of superconductivity and “charge-density-waves” in compounds of the poorly-studied family of bismuthates. This observation opens up new perspectives for a deeper understanding of the phenomenon of high-temperature superconductivity, a topic which is at the core of condensed matter research since more than 30 years. The paper by Nicoletti et al has been published in the PNAS.

Since the beginning of the 20th century, superconductivity had been observed in some metals at temperatures only a few degrees above the absolute zero (minus...

Im Focus: Scientists improve forecast of increasing hazard on Ecuadorian volcano

Researchers from the University of Miami (UM) Rosenstiel School of Marine and Atmospheric Science, the Italian Space Agency (ASI), and the Instituto Geofisico--Escuela Politecnica Nacional (IGEPN) of Ecuador, showed an increasing volcanic danger on Cotopaxi in Ecuador using a powerful technique known as Interferometric Synthetic Aperture Radar (InSAR).

The Andes region in which Cotopaxi volcano is located is known to contain some of the world's most serious volcanic hazard. A mid- to large-size eruption has...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Call for Papers – ICNFT 2018, 5th International Conference on New Forming Technology

16.08.2017 | Event News

Sustainability is the business model of tomorrow

04.08.2017 | Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

 
Latest News

New thruster design increases efficiency for future spaceflight

16.08.2017 | Physics and Astronomy

Transporting spin: A graphene and boron nitride heterostructure creates large spin signals

16.08.2017 | Materials Sciences

A new method for the 3-D printing of living tissues

16.08.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>