Featured Research

from universities, journals, and other organizations

Disrupting antioxidant pathway prevents heart disease caused by reductive stress

Date:
October 11, 2013
Source:
University of Utah Health Sciences
Summary:
Researchers have found that deficiency of an antioxidant response protein called nuclear erythroid-2 like factor-2 (Nrf2) delays or prevents hypertrophic cardiomyopathy.

University of Utah researchers have found that deficiency of an antioxidant response protein called nuclear erythroid-2 like factor-2 (Nrf2) delays or prevents hypertrophic cardiomyopathy, a type of a heart failure in which the heart muscle grows abnormally thick.


This new finding, published in the Oct. 1, 2013, issue of Cardiovascular Research, suggests that restoring the normal balance of reduction-oxidation chemical reactions in the body could prevent heart disease and other conditions caused by reductive stress.
Nuclear erythroid-2 like factor-2 (Nrf2) is a key regulatory protein in the signaling pathway that triggers the body’s primary defense against oxidative stress, a condition where increased production of oxygen-containing free radicals causes cell damage. Many cardiac diseases, including hypertrophic cardiomyopathy, are linked to oxidative stress. However, in a previous study, University of Utah researchers demonstrated that reductive stress, the counterpart of oxidative stress, can also harm the heart due to excessive levels of an antioxidant called reduced glutathione.

“Heart muscle cells, like all cells, are sensitive to shifts in the chemical reactions occurring inside and around them,” says Namakkal S. Rajasekaran, Ph.D., Research Assistant Professor of Internal Medicine at the University of Utah and principal author on the study. “While antioxidants are widely considered an important defense against heart disease, an increasing body of evidence indicates that excessive antioxidant activity can harm the body by creating a condition of reductive stress.”

Rajasekaran and his colleagues studied laboratory mice with heart disease caused by mutations in alpha B-Crystallin, a protein that normally helps other proteins fold inside cells. These mice develop mutant protein aggregation cardiomyopathy (MPAC), a type of heart failure characterized by reductive stress and protein aggregation, the clumping together of misfolded proteins.

“From our earlier research, we know that Nrf2 is a critical regulator of antioxidant activity and sustained activation of Nrf2 causes reductive stress, which contributes to MPAC,” says Rajasekaran. “In this study, we investigated whether disrupting Nrf2 can decrease the activity of antioxidant pathways and prevent the development of cardiac disease.”

The researchers compared two strains of MPAC mice – one with normal Nrf2 and another with Nrf2 deficiency. They found that, while mice with normal Nrf2 developed heart muscle thickening and heart failure, mice that were deficient in Nrf2 did not. They also found that Nrf2 deficiency suppressed reductive stress, reduced cardiac protein aggregation and extended survival.

“Our study demonstrates that preventing excessive antioxidant activity and shifting away from a reductive environment is both necessary and sufficient to prevent harmful cardiac remodeling,” says Rajasekaran.

The body’s antioxidant response provides a natural defense against oxidative stress, but not reductive stress. This new research reveals a novel mechanism for the development and prevention of reductive stress-induced hypertrophic cardiomyopathy and heart failure. Rajasekaran and his colleagues demonstrated that dampening the activity of Nrf-2 decreases chronic reductive stress and prevents improper protein aggregation by restoring the equilibrium of chemical reactions inside heart muscle cells.

“While MPAC is a rare condition, our findings are broadly applicable to heart disease and other conditions caused by protein aggregation, such as Alzheimer’s,” says Rajasekaran. “What this means is that the antioxidant supplements many people take could actually be doing more harm than good, especially if they are taken in excess.”


Story Source:

The above story is based on materials provided by University of Utah Health Sciences. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Kannan, V. R. Muthusamy, K. J. Whitehead, L. Wang, A. V. Gomes, S. E. Litwin, T. W. Kensler, E. D. Abel, J. R. Hoidal, N. S. Rajasekaran. Nrf2 deficiency prevents reductive stress-induced hypertrophic cardiomyopathy. Cardiovascular Research, 2013; 100 (1): 63 DOI: 10.1093/cvr/cvt150

Cite This Page:

University of Utah Health Sciences. "Disrupting antioxidant pathway prevents heart disease caused by reductive stress." ScienceDaily. ScienceDaily, 11 October 2013. <www.sciencedaily.com/releases/2013/10/131011135038.htm>.
University of Utah Health Sciences. (2013, October 11). Disrupting antioxidant pathway prevents heart disease caused by reductive stress. ScienceDaily. Retrieved April 16, 2014 from www.sciencedaily.com/releases/2013/10/131011135038.htm
University of Utah Health Sciences. "Disrupting antioxidant pathway prevents heart disease caused by reductive stress." ScienceDaily. www.sciencedaily.com/releases/2013/10/131011135038.htm (accessed April 16, 2014).

Share This



More Health & Medicine News

Wednesday, April 16, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Outbreak Now Linked To 121 Deaths

Ebola Outbreak Now Linked To 121 Deaths

Newsy (Apr. 15, 2014) The ebola virus outbreak in West Africa is now linked to 121 deaths. Health officials fear the virus will continue to spread in urban areas. Video provided by Newsy
Powered by NewsLook.com
Cognitive Function: Is It All Downhill From Age 24?

Cognitive Function: Is It All Downhill From Age 24?

Newsy (Apr. 15, 2014) A new study out of Canada says cognitive motor performance begins deteriorating around age 24. Video provided by Newsy
Powered by NewsLook.com
How Mt. Everest Helped Scientists Research Diabetes

How Mt. Everest Helped Scientists Research Diabetes

Newsy (Apr. 15, 2014) British researchers were able to use Mount Everest's low altitudes to study insulin resistance. They hope to find ways to treat diabetes. Video provided by Newsy
Powered by NewsLook.com
Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Carpenter's Injury Leads To Hundreds Of 3-D-Printed Hands

Newsy (Apr. 14, 2014) Richard van As lost all fingers on his right hand in a woodworking accident. Now, he's used the incident to create a prosthetic to help hundreds. Video provided by Newsy
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