SummaryThe sirtuin family of nicotinamide adenine dinucleotidedependant (NAD) deacetylases plays an important role in aging and metabolic regulation. In yeast, the

The iron chelator desferrioxamine (DFO) induces accumulation of the hypoxia-inducible factor (HIF-1), a transcription factor that up-regulates genes involved in adaptative responses to hypoxia. This property makes DFO a potential neuroprotector against hypoxic stress. We investigated in rats the effects of DFO on the ventilatory response to mild hypoxic tests and the expression of tyrosine hydroxylase (TH), a target gene of HIF-1. Two protocols were used, the first with repeated injections of 50 mg/kg DFO every 2 days during a 2-week period. This was aimed at define the time course of the ventilatory responses to a hypoxic test. In the second protocol, rats were given a single injection of 300 mg/kg DFO. Every day over 4 days, the hypoxic ventilatory response was recorded before the animal was sacrificed, and Western blot analysis of TH in the dorsal brainstem cardiorespiratory area was performed. DFO produced a delayed increase in the hypoxic ventilatory response, which appeared in the same time window as TH up-regulation (2-3 days after the bolus injection of DFO). This delay suggests a genic effect of the drug that improves the ventilatory response to hypoxia.