Nuclear factor E2 p45-related factor 2 (NRF2) contributes to cellular protection against oxidative insults and chemical carcinogens via transcriptional activation of antioxidant/detoxifying enzymes. To understand the molecular basis of NRF2-mediated protection against oxidative lung injury, pulmonary gene expression profiles were characterized in Nrf2-disrupted (Nrf2 -/-) and wild-type (Nrf2 +/+) mice exposed to hyperoxia or air. Genes expressed constitutively higher in Nrf2 +/+ mice than in Nrf2 -/- mice included antioxidant defense enzyme and immune cell receptor genes. Higher basal expression of heat shock protein and structural genes was detected in Nrf2 -/- mice relative to Nrf2 +/+ mice. Hyperoxia enhanced expression of 175 genes (≥ twofold) and decreased expression of 100 genes (≥50%) in wild-type mice. Hyperoxia-induced upregulation of many well-known/new antioxidant/defense genes (e.g., Txnrd1, Ex, Cp-2) and other novel genes (e.g., Pkc-α, Tcf-3, Ppar-γ) was markedly greater in Nrf2 +/+ mice than in Nrf2 -/- mice. In contrast, induced expression of genes encoding extracellular matrix and cytoskeletal proteins was higher in Nrf2 -/- mice than in Nrf2 +/+ mice. These NRF2-dependent gene products might have key roles in protection against hyperoxic lung injury. Results from our global gene expression profiles provide putative downstream molecular mechanisms of oxygen tissue toxicity.
|Number of pages||19|
|Journal||Free Radical Biology and Medicine|
|Publication status||Published - 2005 Feb 1|
- Free radicals
- Transcription factor
ASJC Scopus subject areas
- Physiology (medical)