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 Building a brain, cell by cell: Researchers make a mini neuron network (of two)
23.05.2018 | Institute of Industrial Science, The University of Tokyo

nachricht Research reveals how order first appears in liquid crystals
23.05.2018 | Brown University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Molecular switch will facilitate the development of pioneering electro-optical devices

A research team led by physicists at the Technical University of Munich (TUM) has developed molecular nanoswitches that can be toggled between two structurally different states using an applied voltage. They can serve as the basis for a pioneering class of devices that could replace silicon-based components with organic molecules.

The development of new electronic technologies drives the incessant reduction of functional component sizes. In the context of an international collaborative...

Im Focus: LZH showcases laser material processing of tomorrow at the LASYS 2018

At the LASYS 2018, from June 5th to 7th, the Laser Zentrum Hannover e.V. (LZH) will be showcasing processes for the laser material processing of tomorrow in hall 4 at stand 4E75. With blown bomb shells the LZH will present first results of a research project on civil security.

At this year's LASYS, the LZH will exhibit light-based processes such as cutting, welding, ablation and structuring as well as additive manufacturing for...

Im Focus: Self-illuminating pixels for a new display generation

There are videos on the internet that can make one marvel at technology. For example, a smartphone is casually bent around the arm or a thin-film display is rolled in all directions and with almost every diameter. From the user's point of view, this looks fantastic. From a professional point of view, however, the question arises: Is that already possible?

At Display Week 2018, scientists from the Fraunhofer Institute for Applied Polymer Research IAP will be demonstrating today’s technological possibilities and...

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...

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

Molecular switch will facilitate the development of pioneering electro-optical devices

24.05.2018 | Power and Electrical Engineering

Research reveals how order first appears in liquid crystals

23.05.2018 | Life Sciences

Space-like gravity weakens biochemical signals in muscle formation

23.05.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>