title: Science review: redox and oxygen-sensitive transcription factors in the regulation of oxidant-mediated lung injury: role for hypoxia-inducible factor-1alpha.
abstract: A progressive rise of oxidative stress due to altered reduction-oxidation (redox) homeostasis appears to be one of the hallmarks of the processes that regulate gene transcription in physiology and pathophysiology. Reactive oxygen species and reactive nitrogen species serve as signaling messengers for the evolution and perpetuation of the inflammatory process that is often associated with the condition of oxidative stress, which involves genetic regulation. Changes in the pattern of gene expression through reactive oxygen species/reactive nitrogen species-sensitive regulatory transcription factors are crucial components of the machinery that determines cellular responses to oxidative/redox conditions. The present review describes the basic components of the intracellular oxidative/redox control machinery and its crucial regulation of oxygen-sensitive and redox-sensitive transcription factors within the context of lung injury. Particularly, the review discusses mechanical ventilation and NF-kappaB-mediated lung injury, ischemia-reperfusion and transplantation, compromised host defense and inflammatory stimuli, and hypoxemia and the crucial role of hypoxia-inducible factor in mediating lung injury. Changes in the pattern of gene expression through regulatory transcription factors are therefore crucial components of the machinery that determines cellular responses to oxidative/redox stress.
authors.affiliation: Severinghaus-Radiometer Research Laboratories, Department of Anesthesia and Perioperative Care, University of California at San Francisco, School of Medicine, San Francisco, California, USA. haddadj@anesthesia.ucsf.edu
authors.forename: John J
authors.initials: JJ
authors.lastname: Haddad
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D000860:Hypoxia / Q000235:genetics / Q000378:metabolism; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D016867:Immunocompromised Host / Q000235:genetics; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D016040:Lung Transplantation / Q000009:adverse effects; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D012121:Respiration, Artificial / Q000009:adverse effects; D012128:Respiratory Distress Syndrome / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C497443:Hif1a protein, mouse; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009687:Nuclear Proteins; D014157:Transcription Factors