Does oxygen tune cellular mechanotransduction?
Does oxygen tune cellular mechanotransduction?
复制标题
氧气可以调节细胞的机械传导吗？
DOI：
10.1152/ajplung.00121.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Hubmayr,RolfD
中科院分区：
文献类型：
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作者：
Hubmayr,RolfD
IN PIONEERING STUDIES CONDUCTED during the latter part of the 19th century, James Lorraine Smith observed that 50% of mice breathing inspired oxygen concentrations between 70 and 80% died within one week (14). He noted that mice had a remarkable ability to recover from the toxic effects of hyperoxia and speculated that the same was true of humans. He has been proven correct since many patients with the acute respiratory distress syndrome recover with near normal lung function despite prolonged mechanical ventilation with high inspired oxygen tensions. In the interim, the effects of hyperoxia on lung cell morphology and function have been described in exquisite detail (4) and are being enriched by an expanding body of knowledge concerning reactive oxygen species (ROS) enzymology (7). The current view on the pathogenesis of pulmonary oxygen toxicity holds that a spatial imbalance between ROS-generating and ROS-scavenging signaling molecules triggers distinct cell death pathways in alveolus resident cells (16). This is often in conjunction with and perpetuated by a cytokine mediated proinflammatory response (1). Yet attempts to translate this knowledge into efficacious lung-protective interventions continue to be frustrated by the plethora of intracellular proteins with putative oxidation motives such as reactive cysteine residues (19). Moreover, the recent focus on physical stress as the cause of ventilator-associated lung injury (VALI) seems to have relegated clinicians’ concerns about oxygen toxicity to one of secondary importance. In the present issue of this journal, Roan and colleagues (13) proffered the intriguing hypothesis that hyperoxia, by virtue of stiffening alveolus resident cells, may increase their susceptibility to wounding by deforming stress. Using atomic force microscopy, they showed that oxygen exposure increases the elastic modulus (a measure of stiffness) of alveolar epithelial cells (AEC) due to actin stress fiber formation and polymerization of the cortical actin network. In an attempt to relate these observations to biophysical lung injury mechanisms, they show that cyclic stretch causes detachment of hyperoxiatreated AEC monolayers from their substratum, in line with cytopathological changes in epithelial and endothelial cells of ventilator-injured lungs (6).The proposed interaction between oxygen exposure and biophysical lung injury mechanisms warrants a brief discussion of cellular micromechanics and the topographical distribution of stress and strain in edematous, mechanically ventilated lungs. Whereas most VALI scholars agree that alveolar overdistension and cyclic recruitment and collapse of unstable lung units are prevalent injury mechanisms, there is less certainty how stresses associated with either mechanism are transduced to generate a specific biological response. Viewed through the lens of cellular stress failure, alveolar overdistension is generally thought to be associated with matrix strains that effect lytic
