Cholesterol Anchor Helps Signaling Proteins Direct Development

October 11, 1996

A quirky genius of the protein family has sprung another surprise on scientists, and its newest stunt has revealed that cholesterol, often villified for its role in heart disease, actually wears a white hat during the earliest stages of life.

In this week's Science, Johns Hopkins and Howard Hughes Medical Institute scientists report that hedgehog proteins, an unusual group of proteins that help shape many features of a developing embryo, pick up molecules of cholesterol to facilitate their work.

Researchers have long known that completely suppressing cholesterol production leads to birth defects in animals; the new work suggests that this may be because lack of cholesterol interferes with the production of hedgehog protein or with the way it spreads through tissues.

"While I do not suggest that expectant mothers switch to a high-fat diet, based exclusively on these results, it might be interesting to take a look clinically at the effect of a mother's diet on the developing fetus," says Philip Beachy, Ph.D., an associate professor of molecular biology and genetics and a Howard Hughes Medical Institute investigator. "I'd be very interested in the effects of cholesterol levels and the presence of substances that affect cholesterol formation."

He cautions that many of the patterning events directed by these proteins take place before most women know they're pregnant.

Hedgehog and other similar proteins act like construction supervisors, helping to direct an organism's growth from a single fertilized egg into a collection of millions of structured, specialized cells. In animal experiments, hedgehog signals can turn on and off genes in many individual cells, coding for special traits needed to help create limbs, eyes, spinal column, or other structures.

In recent years, Hopkins scientists have discovered that hedgehog proteins split in two to activate. During the split, the activated form of the protein, known as the signal, becomes anchored to the surface of the cell that makes it.

"It came as a complete surprise to discover that the cholesterol molecule helps cause the split and then serves as the anchor for the hedgehog signal," says Jeff Porter, Ph.D., a postdoctoral fellow and first author of the paper.

"After spending two years searching for what we thought might be a new molecule, this was like finding out Santa Claus is your dad--hard to believe at first, but after reviewing the data it makes a lot of sense."

The new results could help researchers better understand Smith-Lemli-Opitz syndrome, a serious developmental disorder that strikes approximately one in every 9,000 babies. The disorder disables the body's ability to make cholesterol, producing multiple serious birth defects.

The other study author was Keith E. Young, also of Hopkins and the Howard Hughes Medical Institute.
-end-


Johns Hopkins Medicine

Related Heart Disease Articles from Brightsurf:

Cellular pathway of genetic heart disease similar to neurodegenerative disease
Research on a genetic heart disease has uncovered a new and unexpected mechanism for heart failure.

Mechanism linking gum disease to heart disease, other inflammatory conditions discovered
The link between periodontal (gum) disease and other inflammatory conditions such as heart disease and diabetes has long been established, but the mechanism behind that association has, until now, remained a mystery.

New 'atlas' of human heart cells first step toward precision treatments for heart disease
Scientists have for the first time documented all of the different cell types and genes expressed in the healthy human heart, in research published in the journal Nature.

With a heavy heart: How men and women develop heart disease differently
A new study by researchers from McGill University has uncovered that minerals causing aortic heart valve blockage in men and women are different, a discovery that could change how heart disease is diagnosed and treated.

Heart-healthy diets are naturally low in dietary cholesterol and can help to reduce the risk of heart disease and stroke
Eating a heart-healthy dietary pattern rich in vegetables, fruits, whole grains, low-fat dairy products, poultry, fish, legumes, vegetable oils and nuts, which is also limits salt, red and processed meats, refined-carbohydrates and added sugars, is relatively low in dietary cholesterol and supports healthy levels of artery-clogging LDL cholesterol.

Pacemakers can improve heart function in patients with chemotherapy-induced heart disease
Research has shown that treating chemotherapy-induced cardiomyopathy with commercially available cardiac resynchronization therapy (CRT) delivered through a surgically implanted defibrillator or pacemaker can significantly improve patient outcomes.

Arsenic in drinking water may change heart structure raising risk of heart disease
Drinking water that is contaminated with arsenic may lead to thickening of the heart's main pumping chamber in young adults, according to a new study by researchers at Columbia University Mailman School of Public Health.

New health calculator can help predict heart disease risk, estimate heart age
A new online health calculator can help people determine their risk of heart disease, as well as their heart age, accounting for sociodemographic factors such as ethnicity, sense of belonging and education, as well as health status and lifestyle behaviors.

Wide variation in rate of death between VA hospitals for patients with heart disease, heart failure
Death rates for veterans with ischemic heart disease and chronic heart failure varied widely across the Veterans Affairs (VA) health care system from 2010 to 2014, which could suggest differences in the quality of cardiovascular health care provided by VA medical centers.

Heart failure: The Alzheimer's disease of the heart?
Similar to how protein clumps build up in the brain in people with some neurodegenerative diseases such as Alzheimer's and Parkinson's diseases, protein clumps appear to accumulate in the diseased hearts of mice and people with heart failure, according to a team led by Johns Hopkins University researchers.

Read More: Heart Disease News and Heart Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.