How Cells Change Their Fate

A systems biology approach has identified the key regulators of cell fate determination in heart cells.

AsianScientist (Jan. 15, 2015) – The concentration of the β-adrenergic receptor stimulant affects whether heart cells live or die. The study published in Nature Communications suggests new ways to treat heart disease.

Activation of the β-adrenergic receptor (β-AR) can result in cell death or cell survival, depending on which form of the receptor is engaged. Previous studies have suggested that engagement of the ​β1-adrenergic receptor (​β1-AR) transduces the ‘death’ signal via a cAMP-dependent signalling pathway, while the ​β2-AR transduces the ‘survival’ signal via a Gi-coupled signalling pathway.

However, commonly used heart medication known as beta-blockers non-specifically activate both β1-AR and β2-AR. It is therefore unclear whether these drugs ultimately cause cell death or survival.

Researchers from the Korea Advanced Institute of Science and Technology (KAIST) and Gwangju Institute of Science and Technology (GIST) have now identified the key molecular switches that decide between cell survival and death: the ERK and ICER signal transduction pathways.

Using large-scale computer simulation analyses, they found that weak β-AR stimulations activate ERK signal transduction pathway, increasing the expresssion of the anti-apoptotic Bcl-2 protein and promoting cardiomyocyte survival. On the other hand, strong β-AR stimulations activate ICER signal transduction pathway, reducing Bcl-2 protein expression to promote cardiomyocyte death.

Based on experimentally defined parameters, the researched developed a model to explain the mechanism of a commonly prescribed beta-blocker, ​isoproterenol.

Lead researcher Professor Cho Kwang-Hyun from KAIST said, “This research used systems biology, an integrated, convergence research of IT (information technology) and BT (biotechnology), to successfully identify the mechanism in deciding the fate of cardiomyocytes based on the β-adrenergic receptor signal transduction pathway for the first time.”

“I am hopeful that this research will enable the control of cardiomyocyte survival and death to treat various heart diseases including heart failure.”

The article can be found at: Shin et al. (2015) The Switching Role of β-adrenergic Receptor Signalling in Cell Survival or Death Decision of Cardiomyocytes.

——–

Source: KAIST.
Disclaimer: This article does not necessarily reflect the views of AsianScientist or its staff.

Asian Scientist Magazine is an award-winning science and technology magazine that highlights R&D news stories from Asia to a global audience. The magazine is published by Singapore-headquartered Wildtype Media Group.

Related Stories from Asian Scientist