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Molecule Plays Key Role In Cellular Quality Control Machinery; Findings Carry Implications For Cardiac And Neurological Diseases

Date:
January 10, 2001
Source:
University Of North Carolina School Of Medicine
Summary:
New research at the University of North Carolina at Chapel Hill points to a key role played by a molecular protein in the way body cells maintain quality control when under stress. The findings published this month (January) in Nature Cell Biology add new insights into molecular changes involved in heart attack, heart failure, stroke and some common neurological disorders.

CHAPEL HILL - New research at the University of North Carolina at Chapel Hill points to a key role played by a molecular protein in the way body cells maintain quality control when under stress.

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The findings published this month (January) in Nature Cell Biology add new insights into molecular changes involved in heart attack, heart failure, stroke and some common neurological disorders.

They also add important new knowledge to a fundamental biological problem-how do cells decide to deal with proteins with improperly folded structures, whether to spend time and energy trying to fix them or whether to rapidly get rid of them?

"If you have proteins that become misfolded, they do two things. One, they stick together. Two, they accumulate. And this is the bad thing because there are a lot of diseases that we now understand as misfolded protein accumulation," said cardiologist Cam Patterson, MD, associate professor of medicine at UNC-CH School of Medicine and director of the Program in Molecular Cardiology.

"Many of these are neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease-these are all neurological diseases in which the primary pathology is an accumulation of misfolded proteins. But we're now beginning to appreciate that in the heart, under stressful conditions, misfolded proteins also accumulate and that it impairs cardiac function."

In previous research, Patterson and his colleagues sought genes that might regulate the way myocardium (heart muscle) responds to stress. Last year, they were the first to clone the gene CHIP, whose protein apparently blocked the folding activity of other molecules known as heat shock proteins.

Heat shock proteins are known as chaperones. They recognize misfolded proteins and assist in their conversion to a functional form. When cells are stressed, proteins become improperly folded. Heat shock proteins bind to and orchestrate refolding. "Heat shock proteins also make sure the protein ends up in the right place in the cell where it does what it's supposed to do," Patterson explained.

The study team had hypothesized that CHIP might act a kind of check-point in determining whether heat shock proteins try to refold a particular protein or whether the protein should be targeted for degradation, sent to the cellular trash bin for recycling. According to the new study, CHIP is the protein co-chaperone that makes this triage decision. It apparently provides a direct molecular link between the protein folding and degradation pathways.

"Speaking from my perspective of a cardiovascular biologist and cardiologist, this provides us with an entirely new stress-response system to look at, another molecular pathway we can try to modulate to provide protection to cells during conditions where they're being stressed," Patterson said. "We don't know enough about the system to describe exactly how we would modulate it right now. There's a lot more work to be done. We do have a promising pathway, one that's of particular importance for diseases of the myocardium."

This research was supported by the National Heart, Lung and Blood Institute, NIH.


Story Source:

The above story is based on materials provided by University Of North Carolina School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

University Of North Carolina School Of Medicine. "Molecule Plays Key Role In Cellular Quality Control Machinery; Findings Carry Implications For Cardiac And Neurological Diseases." ScienceDaily. ScienceDaily, 10 January 2001. <www.sciencedaily.com/releases/2001/01/010110074503.htm>.
University Of North Carolina School Of Medicine. (2001, January 10). Molecule Plays Key Role In Cellular Quality Control Machinery; Findings Carry Implications For Cardiac And Neurological Diseases. ScienceDaily. Retrieved November 28, 2014 from www.sciencedaily.com/releases/2001/01/010110074503.htm
University Of North Carolina School Of Medicine. "Molecule Plays Key Role In Cellular Quality Control Machinery; Findings Carry Implications For Cardiac And Neurological Diseases." ScienceDaily. www.sciencedaily.com/releases/2001/01/010110074503.htm (accessed November 28, 2014).

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