Featured Research

from universities, journals, and other organizations

Cell Membrane Protein Reduces Cholesterol

Date:
April 13, 2000
Source:
University Of Wisconsin-Madison
Summary:
A cell membrane protein thought mainly to bind "bad" cholesterol and remove it from circulation also plays a major role in reducing the production of that cholesterol, according to a study published this February in the Journal of Clinical Investigation.

A cell membrane protein thought mainly to bind "bad" cholesterol and remove it from circulation also plays a major role in reducing the production of that cholesterol, according to a study published this February in the Journal of Clinical Investigation.

The UW-Madison study provides new insights into the nature of lipoprotein overproduction in people with familial hypercholesterolemia (FH), an inherited disease that affects one in 500 people. The research also explains how statins, a class of medications taken by several million Americans, work to lower blood cholesterol levels.

Low-density lipoprotein (LDL) carries cholesterol to other cells in the body that need it. People whose blood levels of LDL - the "bad" cholesterol - are too high have an increased risk of heart disease. Individuals with FH have extremely high levels of LDL and are at high risk for heart attacks at an early age.

"In the 1970s researchers discovered that the LDL receptor is responsible for removing most of the cholesterol from blood," according to Alan Attie, a biochemist in the College of Agricultural and Life Sciences. "They showed that a mutation in the gene that codes for the LDL receptor causes FH. Most people thought that the receptor's major function was to clear LDL from blood."

However, scientists later found that people with FH have high LDL levels not only because they clear it from their blood too slowly, but also because they produce too much, Attie says. "Ours is the first study that explains the paradox of why people with FH produce too much LDL," he says. "We showed that functional LDL receptors increase the degradation of apolipoprotein B inside liver cells."

Apolipoprotein B (apoB) is the major protein component of very low-density lipoprotein, which is made by liver cells and converted to LDL in the blood. The rate of apoB production in liver cells - and thus LDL production - is determined by how much apoB is degraded inside the cells before they secrete very low-density lipoprotein into the blood.

Attie led the research team, which included Jaap Twisk, Donald Gillian-Daniel, Angie Tebon, Lin Wang, and Hugh Barrett. Barrett is with the University of Western Australia in Perth; the others were with the UW-Madison at the time the research was done. Twisk is now with the University of Leiden in the Netherlands, and Wang is at the University of California-San Diego in La Jolla, Calif.

The scientists studied liver cells from mice with functional LDL receptors and mice with mutant, nonfunctional receptors. Mice with the mutation showed symptoms analogous to those of people with FH. Their average blood cholesterol level was more than three times that of mice with functioning receptors.

The researchers examined how the presence or absence of LDL receptors affected the secretion of apoB from mouse liver cells. They studied apoB secretion from cells with receptors, from cells with the mutation, and from mutant cells they altered by introducing unusually large numbers of functional receptors.

"We found that although all three types of cells synthesized the same amount of apoB, they degraded different amounts before secreting it," Attie says.

The study found that liver cells with functional receptors degraded 55 percent of the apoB they made before releasing it. Liver cells with FH-like mutant receptors degraded only 20 percent of the apoB they made. However, when large numbers of functional receptors were added to those same mutant cells, they degraded 90 percent of the apoB they synthesized before secreting it.

The results also explain why statin medications - which include the brands Lipitor, Zocor, Pravachol, Lescol, Mevacor and Baycol - are effective in lowering serum LDL levels. As a class of pharmaceuticals, statins inhibit cholesterol production. Liver cells respond to this decrease in cholesterol by producing more LDL receptors on their surfaces. It's long been believed that the additional receptors lowered blood cholesterol levels by clearing LDL-cholesterol from the plasma. Attie notes, however, that statins do not improve the removal of LDL-cholesterol in many people, yet result in lower LDL-cholesterol levels anyway.

"Several studies have shown that statins reduce cholesterol production," Attie says. "We've shown that cells with the most LDL receptors have the lowest production of apoB. By stimulating the production of receptors, statins lower the amount of LDL that is produced."

The UW-Madison scientists are now focusing their efforts on discovering the mechanism by which the LDL receptor limits apoB and LDL production.

The research was supported by state funding to the College of Agricultural and Life Sciences and a grant from the National Heart, Lung and Blood Institute.


Story Source:

The above story is based on materials provided by University Of Wisconsin-Madison. Note: Materials may be edited for content and length.


Cite This Page:

University Of Wisconsin-Madison. "Cell Membrane Protein Reduces Cholesterol." ScienceDaily. ScienceDaily, 13 April 2000. <www.sciencedaily.com/releases/2000/04/000410090157.htm>.
University Of Wisconsin-Madison. (2000, April 13). Cell Membrane Protein Reduces Cholesterol. ScienceDaily. Retrieved August 20, 2014 from www.sciencedaily.com/releases/2000/04/000410090157.htm
University Of Wisconsin-Madison. "Cell Membrane Protein Reduces Cholesterol." ScienceDaily. www.sciencedaily.com/releases/2000/04/000410090157.htm (accessed August 20, 2014).

Share This




More Health & Medicine News

Wednesday, August 20, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: World's Oldest Man Lives in Japan

Raw: World's Oldest Man Lives in Japan

AP (Aug. 20, 2014) A 111-year-old Japanese was certified as the world's oldest man by Guinness World Records on Wednesday. Sakari Momoi, a native of Fukushima in northern Japan, was given a certificate at a hospital in Tokyo. (Aug. 20) Video provided by AP
Powered by NewsLook.com
Ebola-Hit Sierra Leone's Freetown a City on Edge

Ebola-Hit Sierra Leone's Freetown a City on Edge

AFP (Aug. 19, 2014) Residents of Sierra Leone's capital voice their fears as the Ebola virus sweeps through west Africa. Duration: 00:56 Video provided by AFP
Powered by NewsLook.com
101-Year-Old Working Man Has All The Advice You Need

101-Year-Old Working Man Has All The Advice You Need

Newsy (Aug. 19, 2014) Herman Goldman has worked at the same lighting store for almost 75 years. Find out his secrets to a happy, productive life. Video provided by Newsy
Powered by NewsLook.com
Researcher Testing on-Field Concussion Scanners

Researcher Testing on-Field Concussion Scanners

AP (Aug. 19, 2014) Four Texas high school football programs are trying out an experimental system designed to diagnose concussions on the field. The technology is in response to growing concern over head trauma in America's most watched sport. (Aug. 19) Video provided by AP
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