Effect of isoflurne on mRNA expression of HIF target genes.

(A) HIF-1 and HIF-2 have unique, as well as common, target genes. HIF-1 specifically regulates glycolytic genes, including lactate dehydrogenase A (LDHA), phosphoglycerate kinase (PGK), as well as carbonic hydrase-9 (CA IX) whereas HIF-2 exclusively regulates POU transcription factor Oct-4, cyclin D1, and transforming growth factor α (TGF-α). Other hypoxia-inducible genes, such as vascular endothelial growth factor (VEGF), glucose transporter 1 (GLUT1), and EPO are regulated by both HIF-1 and HIF-2. (B, C) 6-week-old BALB/c mice were exposed to 10% O₂ (hypoxia) for 3 hours with or without 0.5% isoflurane and compared with controls. Control mice were exposed to air without isoflurane (normoxia). (D) 6-week-old BALB/c mice were exposed to 0.5% or 1.0% isoflurane in air for 3 hours. Data are presented as mean ± SD (n = 6). The expression levels of EPO, VEGF, LDHA and GLUT1 were assayed using real-time RT-PCR and normalized to that of 18S and expressed relative to the mean of mice exposed to air without isoflurane (normoxia).