Modulation of hemopexin gene expression by physiological oxygen tensions in primary rat hepatocyte cultures

Hyperoxia induces the expression of the hemopexin (Hx) gene in the liver in vivo. To investigate whether the Hx gene is activated by oxygen as such or via H2O2 as an oxygen signal transmitter the effects of arterial and venous O2 tensions as well as different concentrations of H2O2 on Hx mRNA expression were studied. After preculturing primary rat hepatocytes for 24 h at arterial O2 (16%) Hx mRNA was expressed with a maximal level (= 100%), when arterial O2 tension proceeded for 2 h, and to values of approximately 50%, when venous O2 tension (8%) proceeded for 2 h. When hepatocytes were precultured for 24 h under venous O2, Hx mRNA was induced by arterial O2 to values of 60% and under venous O2 to values of approximately 35%. The expression of beta-actin remained unchanged under arterial and venous O2. Exposure of hepatocyte cultures to H2O2 decreased the expression of Hx mRNA in a dose-dependent manner after 2 h, while heme oxygenase-1 (HO-1) mRNA was induced 2.5 fold. The results suggest that O2 per se rather than the reactive oxygen intermediate H2O2 modulates Hx expression.