Signal transduction pathways in hyperoxia-induced lung cell death.
Acute lung injury is an unfortunate consequence of oxygen therapy. Increasing evidence suggests that pulmonary dysfunction resulting from acute oxygen toxicity is at least in part due to the injury and death of lung cells. Studies using morphological and biochemical analyses revealed that hyperoxia-induced pulmonary cell death is multimodal, involving not only necrosis, but also apoptosis. A correlative relationship between the severity of hyperoxic acute lung injury and increased apoptosis has been supported by numerous studies in a variety of animal models, although future experiments are necessary to determine whether it is an actual causal relationship. Altered expression of several apoptotic regulatory proteins, such as p53 and Bcl-2, and DNA damage-induced proteins is associated with hyperoxic cell death and lung injury. Stress-responsive proteins, such as heme oxygenase (HO)-1, have been shown to protect animals against hyperoxic cell injury and death. Redox-sensitive transcription factors and mitogen-activated protein kinase signal transduction pathways may play important roles in regulating the expression of stress-responsive and apoptotic regulatory genes. A better understanding of signal transduction pathways leading to hyperoxic cell death may provide new approaches to the treatment of hyperoxia-induced lung injury.
Mantell
L L
LL
Departments of Thoracic Cardiovascular Surgery, Winthrop-University Hospital, Mineola, New York 11501, USA. lmantell@winthrop.org
Lee
P J
PJ
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D016923:Cell Death; D053938:DNA Fragmentation; D005786:Gene Expression Regulation; D006801:Humans; D018496:Hyperoxia / Q000378:metabolism* / Q000473:pathology*; D008168:Lung / Q000378:metabolism* / Q000473:pathology*; D055370:Lung Injury; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008954:Models, Biological; D018384:Oxidative Stress; D010100:Oxygen / Q000633:toxicity; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
D014157:Transcription Factors; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen