Navigation Links
Protein overexpression at heart of heart failure

Chronic heart failure resulting from dilated cardiomyopathy is rapidly emerging as a disease of epidemic proportions.1 Molecular mechanisms are being studied and advances have been made in a minority of cases, e.g.: the familial forms. Intracellular [Ca2+]i homeostasis is essential for normal cardiac function and integrity, and dysregulation of [Ca2+]i is a hallmark of advanced heart failure.2 The primary trigger for cardiac [Ca2+]i transients is calcium entry through the pore subunit of the voltage-dependent L-type channels (L-VDCC), but their role in heart failure is still controversial. Electrophysiological studies on individual L-VDCCs from failing human heart have revealed an increased single-channel activity but the mechanism for this biophysical phenotype has remained unknown.3,4

In a paper in this week’s PLoS ONE, Roger Hullin of the Swiss Heart Center Bern, Jan Matthes of University of Cologne, Germany, and collaborators in both Germany and the USA demonstrate an up-regulation of expression of an accessory subunit of the L-VDCC complex (beta 2-subunit) that is responsible for the altered channel behavior in human heart failure. Similar changes of both beta-subunit expression and single-channel behavior were also observed in a mouse model of heart failure with cardiac overexpression of the human L-type Ca2+-channel pore. The causal role of the increased beta 2-subunit expression for the “heart failure type?of single L-VDCC characteristics was proven when the authors developed a novel, cardiac-specific, drug-inducible beta 2a subunit overexpression transgenic mouse which was crossbred with the channel pore overexpressing mouse when still nonfailing (“Adaptive phase?. In the nonfailing double transgenics, the induction of beta 2a protein expression increased the activity of single ventricular L-VDCC, rendering these channels phenotypically identical to human and mouse heart failure.

The authors conclude that electrical remodeling of the L-VDCC , based on gene expression changes, is an early step in a cascade ultimately induced in heart failure. This provides a rational framework for novel therapeutic intervention in heart failure.
'"/>

Source:Public Library of Science


Related biology news :

1. Quantum Dots Research Leads to New Knowledge about Protein Binding in Plants
2. Protein discovery could unlock the secret to better TB treatment
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. An HIV Protein Plays a Surprising Role in Gene Activation
5. Protein Packages Found To Activate Genes; May Be What Regulates Development And Disease
6. New SARS Protein Linked To Important Cell Doorway
7. The Shapes Of Life: NIGMS Project Yields More Than 1,000 Protein Structures
8. PANTHER Protein Classification System Database 5.0
9. Duke Chemists Isolating Individual Molecules Of Toxic Protein In Alzheimers, Parkinsons Disease
10. Newly Discovered Compound Blocks Known Cancer-Causing Protein
11. UF Researchers Map Bacterial Proteins That Cause Tooth Loss

Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/28/2016)... GOTHENBURG, Sweden , April 28, 2016 ... 1,491.2 M (139.9), up 966% compared with the first quarter of ... Operating profit totaled SEK 589.1 M (loss: 18.8) and the operating ... SEK 7.12 (loss: 0.32) Cash flow from operations was ... , The 2016 revenue guidance is unchanged, SEK 7,000-8,500 M. ...
(Date:4/15/2016)... 2016 Research and Markets has ... Market 2016-2020,"  report to their offering.  , ... ,The global gait biometrics market is expected to ... period 2016-2020. Gait analysis generates multiple ... used to compute factors that are not or ...
(Date:3/29/2016)... Florida , March 29, 2016 ... the "Company") LegacyXChange "LEGX" and SelectaDNA/CSI Protect are pleased ... in ink used in a variety of writing instruments, ... Buyers of originally created collectibles from athletes on LegacyXChange ... forensic analysis of the DNA. Bill ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... , June 23, 2016  Blueprint Bio, a ... discoveries to the medical community, has closed its Series ... Matthew Nunez . "We have received a ... the capital we need to meet our current goals," ... provide us the runway to complete validation on the ...
(Date:6/23/2016)... Prairie, WI (PRWEB) , ... June 23, 2016 ... ... consultancy focused on quality, regulatory and technical consulting, provides a free webinar ... is presented on July 13, 2016 at 12pm CT at no charge. , ...
(Date:6/22/2016)... , June 22, 2016 Cell Applications, ... allow them to produce up to one billion ... lot within one week. These high-quality, consistent stem ... preparing cells and spend more time doing meaningful, ... a proprietary, high-volume manufacturing process that produces affordable, ...
(Date:6/22/2016)... ... June 22, 2016 , ... ... Port business incubator and current participant in the Phase 1 Ventures program, is ... patients. , Quantitative Radiology Solutions helps physicians make better treatment decisions by ...
Breaking Biology Technology: