Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Jefferson scientists unlocking secrets of cholesterol transport in body

24.02.2004


Scientists at Jefferson Medical College and Jefferson’s Kimmel Cancer Center have discovered one part of the mechanism behind a popular anti-cholesterol drug.



Steven Farber, Ph.D., assistant professor of microbiology and immunology at Jefferson Medical College of Thomas Jefferson University in Philadelphia, Eric Smart, Ph.D., at the University of Kentucky and their co-workers have found that treating hypercholesterolemic mice with the drug ezetimibe (Zetia) disrupts a complex of two proteins in the intestine. At the same time, they used "antisense" molecules to prevent the formation of the complex in zebrafish, resulting in impaired cholesterol absorption in the intestine. The results suggest that these proteins are integral parts of an unidentified cholesterol transport system in the intestine.

A better understanding of the mechanisms behind cholesterol transport and absorption in the intestine could lead to improved therapies for obesity, diabetes and cardiovascular disease.


Dr. Farber and his colleagues report their findings February 23, 2004 in the Proceedings of the National Academy of Sciences. Specifically, the researchers found that two proteins – Caveolin 1 and Annexin 2 – were bound extremely tightly in the intestines. When this association was disrupted in zebrafish embryos, they absorbed a cholesterol "analog" more poorly. The scientists also found a similar close association of these proteins in mouse intestinal cells not found in other cells.

When the team treated mice that were fed a high fat Western diet with Zetia, the two proteins separated. "This was truly an unexpected result," Dr. Farber says. "How cholesterol levels can influence the ability of Zetia to disrupt the complex remains a mystery," he says, adding that both he and Dr. Smart plan to study the question in the near future. Ezetimibe blocks cholesterol absorption in the intestines, and as a result, scientists have inferred the existence of a cholesterol transport system in the intestines. The drug works differently than the popular statins, which inhibit cholesterol synthesis in the liver. But no one has identified molecularly how ezetimibe works.

"We’ve identified the components of the intestine that likely mediate the effect of Zetia," Dr. Farber says. "These proteins probably act as a shuttling system that moves cholesterol through cells." But, he adds, multiple proteins could be involved.

In a recent paper just published in the journal Science, researchers at Schering-Plough Research Institute demonstrated that mice that lack a protein, NPC1L1, absorb very little cholesterol, though the scientists failed to show a direct interaction between Zetia and NPC1L1. Dr. Farber’s group was able to show that Calveolin 1 directly binds to Zetia. "This is a very exciting week in the lipid biology field," he says. "It’s possible that NPC1L1 and our protein complex work together in some yet to be discovered manner."

Given the findings of the two papers, he says, "Now you could try different drugs to see which ones break up the complex, and perhaps not only make better drugs, but improve our understanding of the genes that regulate this process."


Additional Contact Information: Steve Benowitz or Phyllis Fisher
After Hours: 215-955-6060

Steve Benowitz | EurekAlert!
Further information:
http://www.tju.edu/

More articles from Life Sciences:

nachricht Warming ponds could accelerate climate change
21.02.2017 | University of Exeter

nachricht An alternative to opioids? Compound from marine snail is potent pain reliever
21.02.2017 | University of Utah

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Impacts of mass coral die-off on Indian Ocean reefs revealed

21.02.2017 | Earth Sciences

Novel breast tomosynthesis technique reduces screening recall rate

21.02.2017 | Medical Engineering

Use your Voice – and Smart Homes will “LISTEN”

21.02.2017 | Trade Fair News

VideoLinks
B2B-VideoLinks
More VideoLinks >>>