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

E. F. SOTO,* A. L. BERTONE,* J. M. PASQUINI,*J. R. CONNOR AND L. A. PASQUINI*

Portland, Oregan

Congreso; thirty-Seventh Annual Meeting; 2006

American Society of Neurochemistry

The hypoxia is controlled by the hypoxia inducible factor-1 (HIF-1). Its activity is regulated via stability regulation of its alfa subunit. HIF-1alfa destruction is accomplished by a family of enzymes (PHD), which activity depends on the availability of O2, 2- oxoglutarate and Fe2+. PHDs hydroxylate HIF-1alfa to facilitate its ubiquitination. Poly-ubiquitinated HIF-1alfa is then recognized and degraded by the 26S proteasome. Aim: Study the changes in the HIF1alfa stability mediated by the Ub-Proteasome system in iron deficient animals submitted to ischemia-hypoxia treatments.Results: i There was an increase in the levels of HIF1alfa in the iron deficient animals pups submitted or not to ischemia-hypoxia when compared with control animals; ii We found a significant decrease in the proteasome activities evaluated in the solublefraction of brain homogenates from iron deficients animals; iii In iron deficient animals submitted to ischemia-hypoxia, we found a slightly decrease in the chemotryptic and tryptic activities. Conclusions: Increased levels of HIF-1alfa, 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.