Activation of HIF-1alpha mRNA by hypoxia and iron chelator in isolated rat carotid body.

The hypoxia inducible factor-1alpha (HIF-1alpha) protein level is increased by hypoxia and iron chelator (ciclopirox olamine) in isolated rat carotid body (CB) and glomus cells. Reverse transcription and polymerase chain reaction (RT-PCR) are performed to test whether this increase is caused, at least in part, by increased HIF-1alpha gene transcription. HIF-1alpha mRNA levels dose-dependently increased and decreased in the rat CBs incubated for 1 h in a medium saturated with O(2) levels that were varied around nominally normoxic level of 21% in the 0-95% range. The iron chelator, ciclopirox olamine (5 microM), stimulated HIF-1alpha mRNA production under normoxic condition. Thus, in the CB, the main systemic O(2)-sensing organ, HIF-1alpha transcription is regulated by O(2) supply around the normoxic level; this may contribute to cellular and organismal adaptations to chronic changes in ambient O(2).