X-ROS signaling: rapid mechano-chemo transduction in heart
- PMID: 21903813
- DOI: 10.1126/science.1202768
X-ROS signaling: rapid mechano-chemo transduction in heart
Abstract
We report that in heart cells, physiologic stretch rapidly activates reduced-form nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) to produce reactive oxygen species (ROS) in a process dependent on microtubules (X-ROS signaling). ROS production occurs in the sarcolemmal and t-tubule membranes where NOX2 is located and sensitizes nearby ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). This triggers a burst of Ca(2+) sparks, the elementary Ca(2+) release events in heart. Although this stretch-dependent "tuning" of RyRs increases Ca(2+) signaling sensitivity in healthy cardiomyocytes, in disease it enables Ca(2+) sparks to trigger arrhythmogenic Ca(2+) waves. In the mouse model of Duchenne muscular dystrophy, hyperactive X-ROS signaling contributes to cardiomyopathy through aberrant Ca(2+) release from the SR. X-ROS signaling thus provides a mechanistic explanation for the mechanotransduction of Ca(2+) release in the heart and offers fresh therapeutic possibilities.
Comment in
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Cell signaling. Getting to the heart of mechanotransduction.Science. 2011 Sep 9;333(6048):1388-90. doi: 10.1126/science.1212183. Science. 2011. PMID: 21903799 No abstract available.
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