期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 20, 期 6, 页码 929-936出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2013.5517
关键词
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资金
- NIH [R01 HL106059, P01 HL67849, R01 HL36974, RC2 NR011968, 1R01HL105239, U54HD053177]
- Training Program in Cardiovascular Cell Biology [T32 HL072751]
- European Community [HEALTH-F2-2009-241526]
- EUTrigTreat
- Leducq North American-European Atrial Fibrillation Research Alliance
- [K99 HL114879]
Significance: Mechanical activation of reactive oxygen species (ROS) and reactive nitrogen species (RNS) occurs in striated muscle and affects Ca2+ 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) Ca2+ release channels (ryanodine receptors) and tunes Ca2+ signaling during physiological behavior, but excessive X-ROS can promote Ca2+-dependent arrhythmias in pathology. In skeletal muscle, X-ROS sensitizes Ca2+-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. Antioxid. Redox Signal. 20, 929-936.
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