Featured Research

from universities, journals, and other organizations

Post-heart attack biological events provide cardioprotection

Date:
March 13, 2014
Source:
UT Southwestern Medical Center
Summary:
Heart attack and stroke are among the most serious threats to health. But novel research has linked two major biological processes that occur at the onset of these traumatic events and, ultimately, can lead to protection for the heart. On one end of the cascade is the so-called Unfolded Protein Response (UPR), and at the other end are numerous proteins with modified glucose molecules attached to them.

Dr. Joseph A. Hill, (left) Chief of Cardiology and senior author of the study, and Dr. Zhao Wang, a postdoctoral research fellow and the study's first author.
Credit: Image courtesy of UT Southwestern Medical Center

Heart attack and stroke are among the most serious threats to health. But novel research at UT Southwestern Medical Center has linked two major biological processes that occur at the onset of these traumatic events and, ultimately, can lead to protection for the heart.

Related Articles


On one end of the cascade is the so-called Unfolded Protein Response (UPR), and at the other end are numerous proteins with modified glucose molecules attached to them. For years, researchers have made countless observations relating to these opposite ends of the spectrum. Now, researchers at UT Southwestern have discovered a pathway that links these two disparate biological occurrences, which could open the door for new types of treatment.

"Our findings uncover the direct coupling of these two important pathways and raise the prospect of therapeutic manipulation of the UPR to lessen the damage caused by heart attack and stroke," said Dr. Joseph A. Hill, Professor of Internal Medicine and Molecular Biology, and senior author of the study published in the March 13 issue of Cell.

The work by Dr. Hill's team uncovers a previously unrecognized progression following ischemia (when a tissue is deprived of oxygen and nutrients) and reperfusion (when that supply is restored, either spontaneously or therapeutically). Ischemia/reperfusion injury underlies health issues such as heart attack, stroke, and numerous other ailments including diseases of the kidney, liver, skeletal muscles, and more.

When someone suffers a heart attack, it triggers the process of the UPR inside myocytes (heart cells). A link between ischemia/reperfusion and UPR has been suggested previously, but compelling evidence was absent until the Cell study emerged.

Of the three pathways activated within the UPR, the new work implicates IRE1, which produces a molecule called spliced X-box binding protein 1 (Xbp1s), as a direct activator of the hexosamine biosynthetic pathway (HBP). The HBP is responsible for producing modified glucose molecules that couple to numerous proteins, leading to beneficial changes in their function, stability, and location within the cell. This coupling, termed O-GlcNAcylation, has favorable effects on disease-injured cells, including myocytes.

Previously, researchers have verified that the O-GlcNAcylation process provides ample protection for the heart, in addition to many other cell types and tissues. However, what activated the O-GlcNAcylation process was unknown, until now.

"We discovered a linear cascade downstream of ischemia/reperfusion that involves UPR activation, elicitation of Xbp1s, consequent activation of the HBP, and robust cardioprotection," said Dr. Hill, also the Chief of the Division of Cardiology and Director of the Harry S. Moss Heart Center. "It is the first time that researchers have been able to unveil a clear pathway leading to significant cardioprotection, often thought of as the 'holy grail' of cardiology."

While it is clear that the O-GlcNAcylation process protects the heart, we still do not understand how protection is mediated, notes Dr. Hill.

"However, now we know what turns the process on, a finding that points the way to future research and possibly new therapeutic means by which to safeguard the heart," he said.

The study, undertaken by Dr. Zhao Wang, postdoctoral research fellow and first author of the paper, directly raises the question of whether Xbp1s can be manipulated therapeutically. If the body is able to produce more Xbp1s, then doing so would enhance the heart's ability to withstand a heart attack. In fact, using mice engineered to have extra copies of Xbp1s in the heart, Dr. Wang initiated heart attacks that were ultimately smaller and less harmful to the host. Conversely, when he deleted the gene altogether and initiated heart attacks, the effects were much larger and more harmful to the carrier.

"If we can find a way to enhance Xbp1s in the heart, it could be a very significant medical advancement," Dr. Hill said. "At this juncture, however, we're extremely pleased to have uncovered a major pathway that leads to protecting the heart in the face of danger."


Story Source:

The above story is based on materials provided by UT Southwestern Medical Center. Note: Materials may be edited for content and length.


Journal Reference:

  1. Zhao V. Wang, Yingfeng Deng, Ningguo Gao, Zully Pedrozo, Dan L. Li, Cyndi R. Morales, Alfredo Criollo, Xiang Luo, Wei Tan, Nan Jiang, Mark A. Lehrman, Beverly A. Rothermel, Ann-Hwee Lee, Sergio Lavandero, Pradeep P.A. Mammen, Anwarul Ferdous, Thomas G. Gillette, Philipp E. Scherer, Joseph A. Hill. Spliced X-Box Binding Protein 1 Couples the Unfolded Protein Response to Hexosamine Biosynthetic Pathway. Cell, March 2014 DOI: 10.1016/j.cell.2014.01.014

Cite This Page:

UT Southwestern Medical Center. "Post-heart attack biological events provide cardioprotection." ScienceDaily. ScienceDaily, 13 March 2014. <www.sciencedaily.com/releases/2014/03/140313122534.htm>.
UT Southwestern Medical Center. (2014, March 13). Post-heart attack biological events provide cardioprotection. ScienceDaily. Retrieved October 31, 2014 from www.sciencedaily.com/releases/2014/03/140313122534.htm
UT Southwestern Medical Center. "Post-heart attack biological events provide cardioprotection." ScienceDaily. www.sciencedaily.com/releases/2014/03/140313122534.htm (accessed October 31, 2014).

Share This



More Health & Medicine News

Friday, October 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

U.S. Ebola Response Measures Demonstrated

U.S. Ebola Response Measures Demonstrated

AP (Oct. 31, 2014) Officials in the Washington area showed off Ebola response measures being taken at Dulles International Airport and the National Institutes of Health. (Oct. 31) Video provided by AP
Powered by NewsLook.com
Fauci Says Ebola Risk in US "essentially Zero"

Fauci Says Ebola Risk in US "essentially Zero"

AP (Oct. 30, 2014) NIAID Director Anthony Fauci said the risk of Ebola becoming an epidemic in the U.S. is essentially zero Thursday at the Washington Ideas Forum. He also said an Ebola vaccine will be tested in West Africa in the next few months. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Nurse Defies Ebola Quarantine With Bike Ride

Nurse Defies Ebola Quarantine With Bike Ride

AP (Oct. 30, 2014) A nurse who vowed to defy Maine's voluntary quarantine for health care workers who treated Ebola patients followed through on her promise Thursday, leaving her home for an hour-long bike ride. (Oct. 30) Video provided by AP
Powered by NewsLook.com
Pot-Infused Edibles Raise Concerns in Colorado

Pot-Infused Edibles Raise Concerns in Colorado

AFP (Oct. 30, 2014) Colorado may have legalized marijuana for recreational use, but the debate around the decision still continues, with a recent - failed - attempt to ban cannabis-infused edibles. Duration: 01:53 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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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