Featured Research

from universities, journals, and other organizations

Jefferson Scientists Unlocking Secrets Of Cholesterol Transport In Body

Date:
February 24, 2004
Source:
Thomas Jefferson University
Summary:
Scientists at Jefferson Medical College and Jefferson's Kimmel Cancer Center have discovered one part of the mechanism behind a popular anti-cholesterol drug.

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."


Story Source:

The above story is based on materials provided by Thomas Jefferson University. Note: Materials may be edited for content and length.


Cite This Page:

Thomas Jefferson University. "Jefferson Scientists Unlocking Secrets Of Cholesterol Transport In Body." ScienceDaily. ScienceDaily, 24 February 2004. <www.sciencedaily.com/releases/2004/02/040224104815.htm>.
Thomas Jefferson University. (2004, February 24). Jefferson Scientists Unlocking Secrets Of Cholesterol Transport In Body. ScienceDaily. Retrieved April 23, 2014 from www.sciencedaily.com/releases/2004/02/040224104815.htm
Thomas Jefferson University. "Jefferson Scientists Unlocking Secrets Of Cholesterol Transport In Body." ScienceDaily. www.sciencedaily.com/releases/2004/02/040224104815.htm (accessed April 23, 2014).

Share This



More Health & Medicine News

Wednesday, April 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Big Pharma Braces for M&A Wave

Big Pharma Braces for M&A Wave

Reuters - Business Video Online (Apr. 22, 2014) Big pharma on the move as Novartis boss, Joe Jimenez, tells Reuters about plans to transform his company via an asset exchange with GSK, and Astra Zeneca shares surge on speculation that Pfizer is looking for a takeover. Joanna Partridge reports. Video provided by Reuters
Powered by NewsLook.com
How Smaller Plates And Cutlery Could Make You Feel Fuller

How Smaller Plates And Cutlery Could Make You Feel Fuller

Newsy (Apr. 22, 2014) NBC's "Today" conducted an experiment to see if changing the size of plates and utensils affects the amount individuals eat. Video provided by Newsy
Powered by NewsLook.com
How to Master Motherhood With the Best Work/Life Balance

How to Master Motherhood With the Best Work/Life Balance

TheStreet (Apr. 22, 2014) In the U.S., there are more than 11 million couples trying to conceive at any given time. From helping celebrity moms like Bethanny Frankel to ordinary soon-to-be-moms, TV personality and parenting expert, Rosie Pope, gives you the inside scoop on mastering motherhood. London-born entrepreneur Pope is the creative force behind Rosie Pope Maternity and MomPrep. She explains why being an entrepreneur offers the best life balance for her and tips for all types of moms. Video provided by TheStreet
Powered by NewsLook.com
Catching More Than Fish: Ugandan Town Crippled by AIDS

Catching More Than Fish: Ugandan Town Crippled by AIDS

AFP (Apr. 22, 2014) The village of Kasensero on the shores of Lake Victoria was where HIV-AIDS was first discovered in Uganda. Its transient population of fishermen and sex workers means the nationwide programme to combat the virus has had little impact. Duration: 02:30 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins