Peter Rock

Publication Detail

The publication detail shows the title, authors (with indicators showing other profiled authors), information on the publishing organization, abstract and a link to the article in PubMed. This abstract is what is used to create the fingerprint of the publication. If any grants are referenced by the publication, they will be listed here as well.

X-ROS signaling: rapid mechano-chemo transduction in heart.

Benjamin L Prosser; Christopher W Ward; W J Lederer (Profiled Authors: Christopher Ward; W Jonathan Lederer; Benjamin Prosser)

Center for Biomedical Engineering and Technology (BioMET), University of Maryland School of Medicine, Baltimore, MD 21209, USA.
Science (New York, N.Y.) 2011;333(6048):1440-5.

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.

4 Originating Grant

• 1.

  DORSEY, SUSAN G

  TrkB.T1 as a Genetic Disease Modifier of Muscular Dystrophy

  25 September 2009 - 31 July 2011

  NATIONAL INSTITUTE OF NURSING RESEARCH

• 2.

  STANLEY, WILLIAM C

  Training Grant in Cardiac and Vascular Cell Biology

  1 April 2003 - 31 July 2014

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 3.

  Pallone, Thomas L

  Training Grant in Cardiac and Vascular Cell Biology

  1 April 2003 - 31 March 2008

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

• 4.

  Lederer, W Jonathan

  CALCIUM SPARKS IN HEART MUSCLE

  1 December 1986 - 30 November 2003

  NATIONAL HEART, LUNG, AND BLOOD INSTITUTE

Scientific Context

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