SETTON Clara Patricia
congresos y reuniones científicas
Is DMT1 involved in myelination?
MARTINEZ VIVOT ROCÍO; USACH VANINA; GOITIA BELEN; SETTON CLARA PATRICIA
Congreso; 42nd Annual Meeting of the Society for Neuroscience; 2012
Society for Neuroscience
Loss of axonal contact in isolated SCs in vitro or after nerve injury in vivo leads to de-differentiation of these cells. Cultured SCs acquire a phenotype similar to SCs precursors and non-myelin forming SCs. We have described that holotransferrin (hTf) prevented this de-differentiaton (promoted by serum deprivation), while apotransferrin (aTf) was unable to avoid such effect. Bearing in mind that the only difference between aTf and hTf is iron, we analyzed its effect on cultured SCs. Recent results from our group show that iron (as ferric ammonium citrate), in the absence of Tf or serum, prevented SCs from de-differentiating. Furthermore, after iron treatment of SCs, 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, signal that also enables their survival. Whereas Tf-mediated iron uptake is considered the main route of iron uptake in most cells, there is evidence for Tf-independent uptake mechanisms. In the present work we demonstrate the existence of a divalent metal transporter (DMT1) greatly 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. In addition, the existence of its messenger was verified by RT-PCR both in the contralateral and ipsilateral nerves of rats previously submitted to sciatic nerve crush. DMT1 mRNA was found all along the SC progeny (SC precursors (E14), immature SCs (E16, E18, E20) and mature myelinating SCs (P4)). DMT1 expression is increased 14 days after a sciatic nerve crush at the lesion site and distal to it; at 21 and 35 days post crush levels do not return to control ones. 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. Considering that the process of myelination is controlled by this signal, endogenous repair promotion through iron?s prodifferentiating effect could be a promising alternative in the context of demyelinating diseases and remyelinating therapies. Although multiple environmental factors control such repair mechanisms, these results definitely shed light on the matter.