Aggregating instead of stabilizing: New insights into the mechanisms of heart disease
Malformed desmin proteins aggregate with intact proteins of the same kind, thereby triggering skeletal and cardiac muscle diseases, the desminopathies. This was discovered by researchers from the RUB Heart and Diabetes Center NRW in Bad Oeynhausen led by PD Dr. Hendrik Milting in an interdisciplinary research project with colleagues from the universities in Karlsruhe, Würzburg and Bielefeld. They report in the Journal of Biological Chemistry.
Desmin normally forms stabilizing filaments inside of the cells. Different mutations in the DES gene, which contains the blueprint for the protein, induce different muscle diseases. Since chromosomes are always present in pairs, each cell has two DES genes on two different chromosomes. The desminopathies break out even if only one of the DES genes is mutated. With Photo Activation Localization Microscopy (PALM), the interdisciplinary team led by Dr. Milting revealed the mechanism behind this.
If one DES gene is mutated and one intact, a cell produces both malformed and normal proteins. Since not only the mutant desmin proteins clump together, but also the intact exemplars are incorporated into the aggregates, one defective DES gene is enough to trigger the disease. Using the PALM microscope, the researchers attach two different fluorescent molecules to the mutant and the intact proteins. They can turn these markers on and off by laser, effectively flashing them. From the "snapshots" of the intact and the mutated proteins, the computer then calculates a joint picture on which both protein variants can be seen. PALM is a novel microscopy technique that can achieve ten times higher resolution than conventional light microscopy.
In the next step, the research group would like to find out how mutations in the DES gene trigger what is termed arrhythmogenic right ventricular cardiomyopathy, ARVC for short. This rare heart muscle disease is characterized by a severe defect especially to the right ventricle and by heart rhythm problems that can lead to sudden cardiac death due to defects in the cell-cell contacts.
More information: A. Brodehl et al. (2012): Dual-color photoactivation localization microscopy of cardiomyopathy associated desmin mutants, Journal of Biological Chemistry, doi: 10.1074/jbc.M111.313841
Journal reference: Journal of Biological Chemistry
Provided by Ruhr-Universitaet-Bochum
- Researchers link gene mutations to Ebstein's anomaly Feb 16, 2011 | not rated yet | 0
- 'ROCK' off: Study establishes molecular link between genetic defect and heart malformation Feb 06, 2012 | not rated yet | 0
- Parkinson's mutation stunts neurons Nov 22, 2006 | not rated yet | 0
- New gene linked to muscular dystrophy Aug 10, 2009 | not rated yet | 0
- Reprogrammed human adult stem cells rescue diseased muscle in mice Dec 12, 2007 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be a term called "intestinal metaplasia" of stomach
6 hours ago Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
- More from Physics Forums - Medical Sciences
More news stories
Widely available in pharmacies and health stores, phosphatidylserine is a natural food supplement produced from beef, oysters, and soy. Proven to improve cognition and slow memory loss, it's a popular treatment for older ...
Medical research 35 minutes ago | not rated yet | 0 |
Researchers at Emory University have identified a protein that stimulates a pair of "orphan receptors" found in the brain, solving a long-standing biological puzzle and possibly leading to future treatments for neurological ...
Medical research 1 hour ago | not rated yet | 0 |
Australian scientists have charted the path of insulin action in cells in precise detail like never before. This provides a comprehensive blueprint for understanding what goes wrong in diabetes.
Medical research 1 hour ago | 4.5 / 5 (2) | 0 |
Researchers at the University of Illinois at Chicago College of Medicine will study gender differences in how the heart uses and stores fat—its main energy source—and how changes in fat metabolism play ...
Medical research 4 hours ago | not rated yet | 0
Nearly 20 percent of kidneys that are recovered from deceased donors in the U.S. are refused for transplant due to factors ranging from scarring in small blood vessels of the kidney's filtering units to the organ going too ...
Medical research 20 hours ago | 5 / 5 (2) | 0 |
The level of immunity to the recently circulating H7N9 influenza virus in an urban and rural population in Vietnam is very low, according to the first population level study to examine human immunity to the virus, which was ...
1 hour ago | not rated yet | 0 |
You're standing near an airport luggage carousel and your bag emerges on the conveyor belt, prompting you to spring into action. How does your brain make the shift from passively waiting to taking action when ...
11 minutes ago | not rated yet | 0 |
Prostaglandin analogues (PGAs), drugs which lower intraocular pressure, are often the first line of treatment for people with glaucoma, but their use is not without risks. PGAs have long been associated with blurred vision, ...
1 hour ago | not rated yet | 0
Youth who had a schoolmate die by suicide are significantly more likely to consider or attempt suicide, according to a study in published in CMAJ (Canadian Medical Association Journal). This effect can last 2 years or mo ...
46 minutes ago | not rated yet | 0
Most elite athletes consider doping substances "are effective" in improving performance, while recognising that they constitute cheating, can endanger health and entail the obvious risk of sanction. At the same time, the ...
45 minutes ago | not rated yet | 0
Knee replacement surgery is a very common procedure. However, it does not always resolve function or pain in all the recipients of new knees. A study by Robert Barrack, MD and his colleagues from the Washington University ...
1 hour ago | not rated yet | 0