title: Mechanical stretch-induced activation of ROS/RNS signaling in striated muscle.
abstract: CONCLUSIONS
  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.
  
  
  BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: 1 School of Nursing, University of Maryland , Baltimore, Maryland.
authors: Christopher W
authors: CW
authors: Ward
authors: Benjamin L
authors: BL
authors: Prosser
authors: W Jonathan
authors: WJ
authors: Lederer
mesh_terms: D000818:Animals; D006801:Humans; D040542:Mechanotransduction, Cellular / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism; D026361:Reactive Nitrogen Species / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014652:Vascular Diseases / Q000378:metabolism
chemical_list: D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D019255:NADPH Oxidases
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