Does oxygen tune cellular mechanotransduction?

摘要

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.