Featured Research

from universities, journals, and other organizations

Overactive enzyme found in failing hearts

Date:
January 17, 2013
Source:
Ruhr-University Bochum
Summary:
A certain enzyme, the CaM kinase II, keeps the cardiac muscle flexible. By transferring phosphate groups to the giant protein titin, it relaxes the muscle cells. In failing hearts, which don't pump enough blood around the body, the scientists found an overly active CaM kinase II.

Phosphorylation sites in titin: In muscle contraction, the actin (blue) and myosin filaments (green) of the muscle cells move towards each other, so that the muscle is tensed. For this to work, the giant protein titin (red), which is connected to the myosin filament, has to be flexible. How much a heart muscle cell can tension or relax largely depends on the phosphorylation (P) of the PEVK and N2Bus region of titin.
Credit: Copyright Wolfgang Linke

A certain enzyme, the CaM kinase II, keeps the cardiac muscle flexible. By transferring phosphate groups to the giant protein titin, it relaxes the muscle cells. This is reported by researchers led by Prof. Dr. Wolfgang Linke of the Institute of Physiology at the Ruhr Universitδt in the journal Circulation Research. In failing hearts, which don't pump enough blood around the body, the scientists found an overly active CaM kinase II. "The phosphorylation of titin could be a new starting point for the treatment of heart failure" Prof. Linke speculates.

Titin phosphorylation determines the mechanical tension of the muscle cell

Titin is the largest protein in the human body, and it acts like a spring which tenses or relaxes the muscle cell. The attachment of phosphate groups to specific titin sites -- known as phosphorylation -- relaxes the cell. It was already known that the calcium/calmodulin-dependent kinase II, CaM kinase II for short, phosphorylates several proteins in heart cells. Whether it also targets the spring protein titin, has now been examined by the researchers in Bochum.

CaM-Kinase II phosphorylates the giant protein titin

For the study, the researchers used heart cells of "normal" mice, mice that have no CaM kinase II, and mice that produce more CaM kinase II than usual. In cells without the enzyme, titin phosphorylation was reduced by more than 50 percent compared to the normal state. In cells with excess enzyme, however, titin phosphorylation was twice as strong as in normal cells. The CaM kinase II is therefore crucial for the attachment of phosphate groups to the giant protein titin. Linke's team identified two regions within the flexible segment of the titin molecule which are phosphorylated by the enzyme, namely the PEVK and N2Bus region. These sites contain several amino acids of the type serine and threonine, which have changed little in the course of evolution.

The work of the CaM kinase II determines cell stiffness

In further analyses, the research team also showed that a lack or an excess of CaM kinase II affected the stiffness of the muscle cells. Cells without the enzyme were stiffer, cells with the enzyme more flexible. If they added CaM kinase II to cells that were not able to produce the enzyme themselves, these relaxed. In failing human hearts, the team found increased activity of CaM kinase II in comparison with healthy hearts, and thus excessive phosphorylation in the PEVK and N2Bus titin regions. "This seems to alter the mechanical properties of the human heart muscle," says Wolfgang Linke.


Story Source:

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


Journal Reference:

  1. N. Hamdani, J. Krysiak, M. M. Kreusser, S. Neef, C. G. dos Remedios, L. S. Maier, M. Kruger, J. Backs, W. A. Linke. Crucial Role for Ca2 /Calmodulin-Dependent Protein Kinase-II in Regulating Diastolic Stress of Normal and Failing Hearts via Titin Phosphorylation. Circulation Research, 2013; DOI: 10.1161/CIRCRESAHA.111.300105

Cite This Page:

Ruhr-University Bochum. "Overactive enzyme found in failing hearts." ScienceDaily. ScienceDaily, 17 January 2013. <www.sciencedaily.com/releases/2013/01/130117105837.htm>.
Ruhr-University Bochum. (2013, January 17). Overactive enzyme found in failing hearts. ScienceDaily. Retrieved July 30, 2014 from www.sciencedaily.com/releases/2013/01/130117105837.htm
Ruhr-University Bochum. "Overactive enzyme found in failing hearts." ScienceDaily. www.sciencedaily.com/releases/2013/01/130117105837.htm (accessed July 30, 2014).

Share This




More Health & Medicine News

Wednesday, July 30, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) — Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) — Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) — At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Generics Eat Into Pfizer's Sales

Generics Eat Into Pfizer's Sales

Reuters - Business Video Online (July 29, 2014) — Pfizer, the world's largest drug maker, cut full-year revenue forecasts because generics could cut into sales of its anti-arthritis drug, Celebrex. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

    Environment News

    Technology News



      Save/Print:
      Share:  

      Free Subscriptions


      Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

      Get Social & Mobile


      Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

      Have Feedback?


      Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
      Mobile iPhone Android Web
      Follow Facebook Twitter Google+
      Subscribe RSS Feeds Email Newsletters
      Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins