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 New application for acoustics helps estimate marine life populations
16.01.2018 | University of California - San Diego

nachricht Unexpected environmental source of methane discovered
16.01.2018 | University of Washington Health Sciences/UW Medicine

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Scientists decipher key principle behind reaction of metalloenzymes

So-called pre-distorted states accelerate photochemical reactions too

What enables electrons to be transferred swiftly, for example during photosynthesis? An interdisciplinary team of researchers has worked out the details of how...

Im Focus: The first precise measurement of a single molecule's effective charge

For the first time, scientists have precisely measured the effective electrical charge of a single molecule in solution. This fundamental insight of an SNSF Professor could also pave the way for future medical diagnostics.

Electrical charge is one of the key properties that allows molecules to interact. Life itself depends on this phenomenon: many biological processes involve...

Im Focus: Paradigm shift in Paris: Encouraging an holistic view of laser machining

At the JEC World Composite Show in Paris in March 2018, the Fraunhofer Institute for Laser Technology ILT will be focusing on the latest trends and innovations in laser machining of composites. Among other things, researchers at the booth shared with the Aachen Center for Integrative Lightweight Production (AZL) will demonstrate how lasers can be used for joining, structuring, cutting and drilling composite materials.

No other industry has attracted as much public attention to composite materials as the automotive industry, which along with the aerospace industry is a driver...

Im Focus: Room-temperature multiferroic thin films and their properties

Scientists at Tokyo Institute of Technology (Tokyo Tech) and Tohoku University have developed high-quality GFO epitaxial films and systematically investigated their ferroelectric and ferromagnetic properties. They also demonstrated the room-temperature magnetocapacitance effects of these GFO thin films.

Multiferroic materials show magnetically driven ferroelectricity. They are attracting increasing attention because of their fascinating properties such as...

Im Focus: A thermometer for the oceans

Measurement of noble gases in Antarctic ice cores

The oceans are the largest global heat reservoir. As a result of man-made global warming, the temperature in the global climate system increases; around 90% of...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

10th International Symposium: “Advanced Battery Power – Kraftwerk Batterie” Münster, 10-11 April 2018

08.01.2018 | Event News

See, understand and experience the work of the future

11.12.2017 | Event News

Innovative strategies to tackle parasitic worms

08.12.2017 | Event News

 
Latest News

Novel 3-D printing technique yields high-performance composites

16.01.2018 | Materials Sciences

New application for acoustics helps estimate marine life populations

16.01.2018 | Life Sciences

Fast-tracking T cell therapies with immune-mimicking biomaterials

16.01.2018 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>