Desferrioxamine enhances hypoxic ventilatory response and induces tyrosine hydroxylase gene expression in the rat brainstem in vivo

M. V. Nguyen (1, 2) , S. Pouvreau (1, 2) , F. Z. El Hajjaji (1, 2) , M. Denavit-Saubie (2) , J. M. Pequignot (1)

1 PICM - Physiologie intégrative, cellulaire et moléculaire
2 NGI - Neurobiologie génétique et intégrative

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.

Mots clés: iron chelator; cardiorespiratory area; ventilation; HIF-1

Domaines: Autre [q-bio.OT]

M. V. Nguyen, S. Pouvreau, F. Z. El Hajjaji, M. Denavit-Saubie, J. M. Pequignot. Desferrioxamine enhances hypoxic ventilatory response and induces tyrosine hydroxylase gene expression in the rat brainstem in vivo. Journal of Neuroscience Research, 2007, 85 (5), pp.1119 - 1125. ⟨10.1002/jnr.21202⟩. ⟨hal-00188304⟩