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Aggregating instead of stabilizing: New insights into the mechanisms of heart disease

Date:
May 23, 2012
Source:
Ruhr-Universitaet-Bochum
Summary:
Researchers have gained new insights into the mechanisms of heart disease.

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.
Credit: Andreas Brodehl/Per Niklas Hedde

RUB researchers have gained new insights into the mechanisms of heart disease.

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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.

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.


Story Source:

The above story is based on materials provided by Ruhr-Universitaet-Bochum. Note: Materials may be edited for content and length.


Journal Reference:

  1. A. Brodehl, P. N. Hedde, M. Dieding, A. Fatima, V. Walhorn, S. Gayda, T. Saric, B. Klauke, J. Gummert, D. Anselmetti, M. Heilemann, G. U. Nienhaus, H. Milting. Dual Color Photoactivation Localization Microscopy of Cardiomyopathy-associated Desmin Mutants. Journal of Biological Chemistry, 2012; 287 (19): 16047 DOI: 10.1074/jbc.M111.313841

Cite This Page:

Ruhr-Universitaet-Bochum. "Aggregating instead of stabilizing: New insights into the mechanisms of heart disease." ScienceDaily. ScienceDaily, 23 May 2012. <www.sciencedaily.com/releases/2012/05/120523102146.htm>.
Ruhr-Universitaet-Bochum. (2012, May 23). Aggregating instead of stabilizing: New insights into the mechanisms of heart disease. ScienceDaily. Retrieved November 1, 2014 from www.sciencedaily.com/releases/2012/05/120523102146.htm
Ruhr-Universitaet-Bochum. "Aggregating instead of stabilizing: New insights into the mechanisms of heart disease." ScienceDaily. www.sciencedaily.com/releases/2012/05/120523102146.htm (accessed November 1, 2014).

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