Changes in the hypoxia inducible factor-1 stability in iron deficient rats submitted to neonatal ischemia-hypoxia

BERTONE AL, SOTO E, PASQUINI J, CONNOR J, PASQUINI LA

Pinamar, Buenos Aires, Argentina

Congreso; SAIB -PABMB-SAN; 2005

SAIB -PABMB-SAN

The hypoxia is controlled by the hypoxia inducible factor-1 (HIF-1). Its activity is regulated via stability regulation of its aƒnsubunit.  HIF-1aƒn destruction is accomplished by a family of enzymes (PHD), which activity depends on the availability of O2, 2-oxoglutarate and Fe2+. PHDs hydroxylate HIF-1aƒn to facilitate its ubiquitination. Poly-ubiquitinated HIF-1a ƒnis then recognized and degraded by the 26S proteasome. Aim: study the changes in the HIF1a stability mediated by the Ub-Proteasome system in iron deficient animals submitted to ischemia-hypoxia treatments. Results: 1) There was an increase in the levels of HIF1aƒwƒn in the iron deficient animals pups submitted or not to ischemia-hypoxia when compared with control animals 2) We found a significant decrease in the proteasome activities evaluated in the soluble fraction of brain homogenates from iron deficients animals. 3) In iron deficient animals submitted to ischemia-hypoxia, we found a slightly decrease in the chemotryptic and tryptic activities. Conclusions: Increased levels of HIF-1a, could be explained by the changes in Ub-proteasome system activity and by iron depletion Additional experiments will be performed in order to confirm our hypothesis.