Manipulation of gene expression by oxygen: a primer from bedside to bench

For nearly 100 y, pediatricians have regularly used oxygen to treat neonatal and childhood diseases. During this time, it has become clear that oxygen is toxic and that overzealous use can lead to significant morbidity. As we have learned more about the appropriate clinical indications for oxygen therapy, studies at the bench have begun to elucidate the molecular mechanisms by which cells respond to hyperoxia. In this review, we discuss transcription factors whose activity is regulated by oxygen, including nuclear factor, erythroid 2-related factor 2 (Nrf2), activator protein 1 (AP-1), p53, nuclear factor kappaB (NF-kappaB), signal transducers and activators of transcription protein (STAT), and ccat/enhancer binding protein (CEBP). Special attention is paid to the mechanisms by which hyperoxia affects these transcription factors in the lung. Finally, we identify downstream targets of these transcription factors, with a focus on heme oxygenase-1. A better understanding of how oxygen affects various signaling pathways could lead to interventions aimed at preventing hyperoxic injury.