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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6048
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pubmed:dateCreated |
2011-9-9
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pubmed:abstractText |
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.
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pubmed:grant |
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
1095-9203
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
9
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pubmed:volume |
333
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1440-5
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pubmed:meshHeading |
pubmed-meshheading:21903813-Animals,
pubmed-meshheading:21903813-Calcium,
pubmed-meshheading:21903813-Calcium Signaling,
pubmed-meshheading:21903813-Electric Stimulation,
pubmed-meshheading:21903813-Mechanotransduction, Cellular,
pubmed-meshheading:21903813-Membrane Glycoproteins,
pubmed-meshheading:21903813-Mice,
pubmed-meshheading:21903813-Mice, Inbred C57BL,
pubmed-meshheading:21903813-Mice, Inbred mdx,
pubmed-meshheading:21903813-Microtubules,
pubmed-meshheading:21903813-Muscular Dystrophy, Animal,
pubmed-meshheading:21903813-Myocardial Contraction,
pubmed-meshheading:21903813-Myocytes, Cardiac,
pubmed-meshheading:21903813-NADPH Oxidase,
pubmed-meshheading:21903813-Oxidation-Reduction,
pubmed-meshheading:21903813-Rats,
pubmed-meshheading:21903813-Rats, Sprague-Dawley,
pubmed-meshheading:21903813-Reactive Oxygen Species,
pubmed-meshheading:21903813-Ryanodine Receptor Calcium Release Channel,
pubmed-meshheading:21903813-Sarcolemma,
pubmed-meshheading:21903813-Sarcoplasmic Reticulum,
pubmed-meshheading:21903813-Signal Transduction
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pubmed:year |
2011
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pubmed:articleTitle |
X-ROS signaling: rapid mechano-chemo transduction in heart.
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pubmed:affiliation |
Center for Biomedical Engineering and Technology (BioMET), University of Maryland School of Medicine, Baltimore, MD 21209, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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