An overactive enzyme found in failing hearts. A surprising new finding by researchers at the Institute of Physiology at Ruhr Universität in Germany shows that an overactive enzyme may hold the key to heart failure.
An enzyme called CaM kinase II keeps cardiac muscle relaxed and flexible by chemically bonding phosphate groups to the giant protein titin. So when a heart starts to fail and is unable to pump enough blood around the body, the research team figured an overly active CaM kinase II and overphosphorylation of titin may be the underlying reason why.
Titin is the largest protein in the human body and acts like a spring to tense or relax muscle cells. When phosphate groups bind to specific locations on titin in a process known as phosphorylation, muscle cells become relaxed.
In their study, researchers at Ruhr Universität examined whether CaM kinase II phosphorylates the titin using heart cells from normal mice, along with those from mice that have no CaM kinase II and mice that make more CaM kinase II than normal.
They found that in mouse cells without the CaM kinase II enzyme, titin phosphorylation was reduced by more than 50% compared to normal mouse cells. On the other hand, in cells with extra enzyme, titin phosphorylation was twice as strong as in normal cells. This clearly shows that CaM kinase II is crucial for the chemical bonding of phosphate groups to titin.
Further, the research team showed that lack or an excess of CaM kinase II affected the flexibility and stiffness of muscle cells. While cells without the enzyme were stiffer, cells that contained the active enzyme were noticeably more flexible. And finally - if the researchers added CaM kinase II to cells that didn’t make the enzyme themselves, they became relaxed.
In failing human hearts, the Ruhr Universität research team found increased CaM Kinase II enzyme activity when compared to healthy human hearts. This means muscle cells in failing human hearts are likely to be more relaxed than normal, similar to mice cells in the study - which might hold the key to why these hearts fail.
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