Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Desminopathies: RUB researchers gain new insights into the mechanisms of heart disease

23.05.2012
Aggregating instead of stabilizing
Mutated and intact proteins of the cytoskeleton form abnormal aggregates

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.


Using Photo Activation Localization Microscopy (PALM), ten times the resolution (right) of conventional light microscopy (left) is achieved. The image shows a desmin filament which was taken with a conventional microscope and with the high-resolution PALM microscope. Illustration: Andreas Brodehl/Per Niklas Hedde

One defective gene is enough

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.

Making mutated and intact proteins visible

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.

Further research projects

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.

Bibliographic record

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

Further information

PD Dr. Hendrik Milting, Erich and Hanna Klessmann - Institute for Cardiovascular Research and Development, Heart and Diabetes Center NRW, Ruhr-Universität Bochum, Georgstraße 11, Bad Oeynhausen, Tel. 05731/97-3510

HMilting@hdz-nrw.de

Editor: Dr. Julia Weiler

Dr. Josef König | idw
Further information:
http://www.ruhr-uni-bochum.de

More articles from Health and Medicine:

nachricht A 'half-hearted' solution to one-sided heart failure
24.11.2017 | Boston Children's Hospital

nachricht New study points the way to therapy for rare cancer that targets the young
22.11.2017 | Rockefeller University

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: New proton record: Researchers measure magnetic moment with greatest possible precision

High-precision measurement of the g-factor eleven times more precise than before / Results indicate a strong similarity between protons and antiprotons

The magnetic moment of an individual proton is inconceivably small, but can still be quantified. The basis for undertaking this measurement was laid over ten...

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

IceCube experiment finds Earth can block high-energy particles from nuclear reactions

24.11.2017 | Physics and Astronomy

A 'half-hearted' solution to one-sided heart failure

24.11.2017 | Health and Medicine

Heidelberg Researchers Study Unique Underwater Stalactites

24.11.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>