INVESTIGADORES
SETTON Clara Patricia
congresos y reuniones científicas
Título:
?Alternative iron uptake in the peripheral nervous system?
Autor/es:
MARTINEZ VIVOT ROC√ćO; USACH VANINA; LAVALLE LUCIA; SETTON CLARA PATRICIA
Lugar:
Atenas
Reunión:
Congreso; 23rd Biennial Meeting of the ISN-ESN; 2011
Institución organizadora:
International Society for Neurochemistry
Resumen:
Although the molecular identity of the axonal signal that induces Schwann cell?s phenotype (SCs) is unknown, there is significant information on the intracellular signals and transcription factors that are involved in the myelination of SCs. Loss of axonal contact in isolated SCs in vitro or after nerve injury in vivo leads to de-differentiation of SCs. We have described that holotransferrin (hTf), (iron bound apotransferrin (aTf)) prevented this de-differentiaton, while aTf was unable to avoid such effect. We analyzed the effect of iron on cultured SCs where we show that iron (as ferric ammonium citrate), in the absence of Tf or serum, also prevented SCs from de-differentiating. Furthermore, we demonstrated that intracellular signals towards differentiation become activated or stabilized through cAMP release, PKA activation and CREB phosphorylation. The prodifferentiating effect of iron and hTf suggests their participation in the axonal signal that occurs during the maturation of SCs, which enables their survival. Whereas Tf-mediated iron uptake is considered the main route of iron uptake, there is evidence for Tf-independent mechanisms. In the present work we demonstrate the existence of a divalent metal transporter (DMT1) highly described in literature as an iron metabolism key player, but never before within the PNS context. The presence of DMT1 was demonstrated in nerve homogenate, isolated adult-rat myelin and cultured SCs by Western Blot analysis and confirmed through its co-localization with S-100 (SC marker) by immunocytochemistry. Furthermore, the existence of its messenger was verified by RT-PCR both in the contralateral and ipsilateral nerves of rats submitted to sciatic nerve crush. Moreover, DMT1 mRNA was found along the SC progeny (SC precursors (E14), immature SCs (E16, E18, E20) and mature myelinating SCs (P4)). These data allow us to confirm the existence of a Tf independent iron uptake mechanism in SCs, validating the role of iron in the axonal signal.