Features | Partner Sites | Information | LinkXpress
Sign In
Demo Company

Newly Discovered Protein Mechanism Protects Cells during Injury

By BiotechDaily International staff writers
Posted on 19 Jun 2012
Investigators have identified a new function for a protein that protects cells during injury and could ultimately transform into treatment for disorders ranging from cardiovascular disease to Alzheimer’s.

Researchers reported online June 7, 2012, in the journal Cell that a type of protein called thrombospondin activates a protective pathway that prevents heart cell damage in mice undergoing simulated extreme hypertension, cardiac pressure overload, and heart attack.

“Our results suggest that medically this protein could be targeted as a way to help people with many different disease states where various organs are under stress,” said Jeffery Molkentin, PhD, lead investigator and a researcher from Cincinnati Children’s Hospital Medical Center (OH, USA) and the Howard Hughes Medical Institute (Chevy Chase, MD, USA). “Although more study is needed to determine how our findings might be applied clinically, a possible therapeutic strategy could include a drug or gene therapy that induces overexpression of the protein in tissues or organs undergoing injury.”

Thrombospondin (Thbs) proteins are generated by the body in cells where tissues are being injured, reconfigured or remodeled, such as in chronic cardiac disease. They appear in part of the cell’s internal machinery called the endoplasmic reticulum. There, Thbs activated a stress response process to regulate production of other proteins and help correct or lose cells of proteins that misfold and lose their form and planned function. Misfolded proteins help fuel tissue damage and organ dysfunction.

The researchers honed in on how one thrombospondin protein (Thbs4) triggers cellular stress responses in mice bred to overexpress the protein in heart cells. They compared how the hearts of the Thbs4-positive mice responded to simulated stress and injury to mice not bred to overexpress cardiac-specific Thbs4.

Overexpression of Thbs4 had no effect on the animals prior to cardiac stress--although during simulated hypertension and cardiac infarction the protein reduced injury and protected them from death. Mice not bred for Thbs4 overexpression were extremely sensitive to cardiac injury, according to Dr. Molkentin, a member of the division of molecular cardiovascular biology and Cincinnati Children’s Heart Institute.

The researchers reported that overexpressed Thbs4 enhanced the ability of heart cells to secrete supportive proteins, resolve misfolded proteins, and correctly reconstruct extracellular matrix--connective tissues that help provide the heart with a functional form and structural integrity.

Vital to the stress response process was Thbs4 activating and regulating a transcription factor called Aft6alpha. Transcription factors help decode genetic instructions of other genes to control their expression. In the case of Aft6alpha in the heart, it helps mediate repair processes. When Aft6alpha is activated by Thbs4, the endoplasmic reticulum in cells expands and the production of chaperone molecules and other repair proteins is enhanced. Mice bred not to overexpress cardiac Thbs4 did not exhibit activated Aft6alpha or robust repair processes following cardiac injury, leading to their poor outcomes.

According to Dr. Molkentin, the investigators continue to analyze the Thbs-dependent stress response pathway to better clarify the involved mechanisms. This includes determining how the pathway affects laboratory models of neurodegenerative diseases like Parkinson’s, Alzheimer’s, and amyotrophic lateral sclerosis.

Related Links:

Cincinnati Children’s Hospital Medical Center
Howard Hughes Medical Institute



view channel
Image: A new catalyst that improved the sensitivity of the standard PSA ELISA test by about 110-fold was made of palladium nanocubes coated with iridium (Photo courtesy of Dr. Xiaohu Xia, Michigan Technological University).

Peroxidase Mimic Outperforms Natural Horseradish Peroxidase in ELISA Test

A test-of-concept study demonstrated that a synthetic catalyst that mimics the action of horseradish peroxidase (HRP) could increase the sensitivity of a colorimetric enzyme-linked immunosorbent assay... Read more

Drug Discovery

view channel
Image: Endoscopic image of a bowel section known as the sigmoid colon afflicted with ulcerative colitis. The internal surface of the colon is blotchy and broken in places (Photo courtesy of Wikimedia Commons).

Orally Delivered Curcumin-Loaded Microparticles Effectively Treat Mouse Model of Ulcerative Colitis

Microparticles (MPs) loaded with the efficient anti-inflammatory agent curcumin were found to effectively treat a mouse model of ulcerative colitis. Ulcerative colitis is a chronic relapsing disease... Read more

Lab Technologies

view channel

New Genomic Research Kit Simplifies Exome Studies

An exciting new tool is now available for biotech researchers working in the field of genomic analysis. The human exome is critical to our genetic make-up and is generally accepted as having the greatest influence on how the genetic blueprint is utilized. The exome is defined as all coding exons in the genome and is... Read more


view channel

Collaboration Agreement to Boost Discovery of Fully Human Antibodies for Therapeutic Use

The discovery of fully human antibodies for therapeutic use will be boosted by a recently announced collaboration between a major university research center and a dynamic biopharmaceutical development company. Regeneron Pharmaceuticals, Inc. (Tarrytown, New York, USA) and The Experimental Therapeutics Institute (ETI)... Read more


17 Oct 2015 - 21 Oct 2015
25 Oct 2015 - 29 Oct 2015
16 Nov 2015 - 19 Nov 2015
Copyright © 2000-2015 Globetech Media. All rights reserved.