AsianScientist (Nov. 7, 2016) – Researchers in Japan have identified a protein that stops heart muscle cells from increasing in size when the heart is under stress. Their work was published in Scientific Reports.
Cardiac hypertrophy occurs when the heart muscle is placed under higher stress than normal and needs to develop greater bulk to deal with this, both at the level of the whole organ or at the level of single cells. Although the swelling of heart muscle cells (cardiomyocytes) has been investigated, understanding of the molecular mechanisms that promote and inhibit this process has remained limited.
Researchers at Osaka University have now identified that a protein called Btg2 acts as a global regulator of RNA within cardiomyocytes. Using single-cell imaging, they showed that the over-expression of Btg2 within stressed cardiac tissue reduced the size of cardiomyocytes, showing that Btg2 negatively regulates cardiac hypertrophy.
“We first focused on the targets of the protein Myc, which is known to increase the size and anabolic activity of cardiomyocytes,” said corresponding author Shuichiro Higo. “We found that Btg2 was especially strongly induced by Myc, but that these two proteins had opposite effects on the level of RNA in these cells. This suggests they are on opposing sides of a system regulating protein production and cell size.”
Single-cell imaging helped the team identify where Btg2 was active within the cell. Combined with functional analysis, they determined the mechanisms by which Btg2 induces a reduction in global RNA level. Their findings show that Btg2 interacts with cellular machinery that breaks down RNA, which explains its association with reduced protein production and, thus, smaller cells.
“We now have a much better understanding of the mechanisms by which heart cells can not only expand in response to stress, but also limit this expansion,” Higo said. “We may be able to harness these mechanisms to reduce some of the problems associated with long-term cardiac hypertrophy and heart disease.”
The article can be found at: Masumura et al. (2016) Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA.
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Source: Osaka University; Photo: Shutterstock.
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