title: Reactive oxygen species induce a Ca(2+)-spark increase in sensitized murine airway smooth muscle cells.
abstract: The level of reactive oxygen species (ROS) and the activity of spontaneous, transient, localized Ca(2+) increases (known as Ca(2+) sparks) in tracheal smooth muscle cells (TSMCs) in an experimental allergic asthma mouse model has not yet been investigated. We used laser confocal microscopy and fluorescent dyes to measure ROS levels and Ca(2+) sparks, and we found that both events were significantly increased in TSMCs obtained from ovalbumin (OVA)-sensitized/-challenged mice compared with control mice. ROS levels began to increase in TSMCs after the first OVA challenge, and this increase was sustained. However, this elevation and Ca(2+)-spark increase was abolished after the administration of the ROS scavenger N-acetylcysteine amide (NACA) for 5days. Furthermore, a similar inhibition was also observed following the direct perfusion of NACA into cells isolated from the (OVA)-sensitized mice that were not treated with NACA. Moreover, we used 0.1-mM caffeine treatment to increase the Ca(2+) sparks in single TSMCs and observed cell shortening. In addition, we did not find increases in the mRNA levels of ryanodine (RyRs) and inositol 1,4,5-trisphosphate (IP3Rs) receptors in the tracheal smooth muscle cells of (OVA)-sensitized mice compared with controls. We concluded that ROS and Ca(2+) sparks increased in (OVA)-sensitized TSMCs. We found that ROS induces Ca(2+) sparks, and increased Ca(2+) sparks resulted in the contraction of (OVA)-sensitized TSMCs, resulting in the generation of airway hyperresponsiveness (AHR). This effect may represent a novel mechanism for AHR pathogenesis and might provide insight into new methods for the clinical prevention and treatment of asthma and asthmatic AHR.
authors.affiliation: Institute for Medical Biology, College of Life Sciences, South-Central University for Nationalities, Wuhan 430074, China.
authors.forename: Qing-Rong
authors.initials: QR
authors.lastname: Tuo
authors.forename: Yun-Fei
authors.initials: YF
authors.lastname: Ma
authors.forename: Weiwei
authors.initials: W
authors.lastname: Chen
authors.forename: Xiao-Jing
authors.initials: XJ
authors.lastname: Luo
authors.forename: Jinhua
authors.initials: J
authors.lastname: Shen
authors.forename: Donglin
authors.initials: D
authors.lastname: Guo
authors.forename: Yun-Min
authors.initials: YM
authors.lastname: Zheng
authors.forename: Yong-Xiao
authors.initials: YX
authors.lastname: Wang
authors.forename: Guangju
authors.initials: G
authors.lastname: Ji
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D051379:Mice; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014132:Trachea / Q000166:cytology / Q000378:metabolism*
chemical_list: D017382:Reactive Oxygen Species; D010047:Ovalbumin; D002118:Calcium