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Antioxid Redox Signal. 2014 Feb 20;20(6):929-36. doi: 10.1089/ars.2013.5517. Epub 2014 Jan 3.

Mechanical stretch-induced activation of ROS/RNS signaling in striated muscle.

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1
1 School of Nursing, University of Maryland , Baltimore, Maryland.

Abstract

SIGNIFICANCE:

Mechanical activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs in striated muscle and affects Ca(2+) signaling and contractile function. ROS/RNS signaling is tightly controlled, spatially compartmentalized, and source specific.

RECENT ADVANCES:

Here, we review the evidence that within the contracting myocyte, the trans-membrane protein NADPH oxidase 2 (Nox2) is the primary source of ROS generated during contraction. We also review a newly characterized signaling cascade in cardiac and skeletal muscle in which the microtubule network acts as a mechanotransduction element that activates Nox2-dependent ROS generation during mechanical stretch, a pathway termed X-ROS signaling.

CRITICAL ISSUES:

In the heart, X-ROS acts locally and affects the sarcoplasmic reticulum (SR) Ca(2+) release channels (ryanodine receptors) and tunes Ca(2+) signaling during physiological behavior, but excessive X-ROS can promote Ca(2+)-dependent arrhythmias in pathology. In skeletal muscle, X-ROS sensitizes Ca(2+)-permeable sarcolemmal "transient receptor potential" channels, a pathway that is critical for sustaining SR load during repetitive contractions, but when in excess, it is maladaptive in diseases such as Duchenne Musclar dystrophy.

FUTURE DIRECTIONS:

New advances in ROS/RNS detection as well as molecular manipulation of signaling pathways will provide critical new mechanistic insights into the details of X-ROS signaling. These efforts will undoubtedly reveal new avenues for therapeutic intervention in the numerous diseases of striated muscle in which altered mechanoactivation of ROS/RNS production has been identified.

PMID:
23971496
PMCID:
PMC3924793
DOI:
10.1089/ars.2013.5517
[Indexed for MEDLINE]
Free PMC Article
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