OLIGODENDROGLIAL CELLS SUBMITTED TO HYPOXIA ARE LESS VULNERABLE TO DAMAGE IN THE PRESENCE OF INTRACELLULAR IRON CHELATORS

BERTONE UÑA, A.L., SOTO, E., PASQUINI, J.M., PASQUINI, L.A.

San Antonio, Texas. EEUU

Congreso; 39 th Annual Meeting American Society for Neurochemistry; 2008

AMERICAN SOCIETY FOR NEUROCHEMISTRY

The transcriptional activator HIF-1 plays an essential role in oxygen sensing. HIF-1 registers changes and coordinates answers that allow cells to survive to hypoxia (H). HIF-1 consists of alpha and betha subunits. HIF-1alpha degradation is accomplished by prolilhidroxylases (PHD). PHDs hydroxylate HIF-1alpha to facilitate its ubiquitination and polyubiquitinated HIF-1alpha is then recognized and degraded by the 26S proteasome. Using iron chelators like desferrioxamine (DFO), TPEN, or dihidroxibenzoic acid (DHB), it is possible to stabilize HIF-1alpha. Aim: To study the consequences of hypoxia treatment on oligodendroglial cell viability in cultures at different stages of their maturation in the presence and absence of TPEN, DFO or DHB. Results: Late oligodendroglial progenitor cells (LPCs) are more vulnerable to hypoxia than less differentiated precursors and they are significantly protected by addition to the cultures of the intracellular iron chelator TPEN. Conclusions: the increase in survival rate induced by the treatment with TPEN, in LPCs submitted to hypoxia, could be related to its action as an intracellular iron chelator. The greater vulnerability to hypoxia of LPCs in comparison with that observed in less differentiated precursors agrees with previous data that relate the existence of a temporary ‘‘vulnerability window’’ in these cells.It is tempting to speculate that a decrease in iron levels trigger protective mechanisms in oligodendroglial cells submitted to hypoxia, as a consequence of a stabilization of HIF-1alpha and a decreased production of oxidative species.Aim: To study the consequences of hypoxia treatment on oligodendroglial cell viability in cultures at different stages of their maturation in the presence and absence of TPEN, DFO or DHB. Results: Late oligodendroglial progenitor cells (LPCs) are more vulnerable to hypoxia than less differentiated precursors and they are significantly protected by addition to the cultures of the intracellular iron chelator TPEN. Conclusions: the increase in survival rate induced by the treatment with TPEN, in LPCs submitted to hypoxia, could be related to its action as an intracellular iron chelator. The greater vulnerability to hypoxia of LPCs in comparison with that observed in less differentiated precursors agrees with previous data that relate the existence of a temporary ‘‘vulnerability window’’ in these cells.It is tempting to speculate that a decrease in iron levels trigger protective mechanisms in oligodendroglial cells submitted to hypoxia, as a consequence of a stabilization of HIF-1alpha and a decreased production of oxidative species.