Iron and holotransferrin induce cAMP-dependent differentiation of Schwann cells

C SALIS; DAVIO C; USACH V; URTASUN N; GOITIA B; MARTINEZ VIVOT R; PASQUINI JM; SETTON-AVRUJ, CP

NEUROCHEMISTRY INTERNATIONAL

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2012 vol. 61 p. 798 - 806

0197-0186

The differentiation of myelin-forming Schwann cells (SC) is completed with the appearance of myelin proteins MBP and P0 and a concomitant downregulation of markers GFAP and p75NTR, which are expressed by immature and adult non-myelin-forming SC. We have previously demonstrated that holotransferrin (hTf) can prevent SC dedifferentiation in culture (Salis et al., 2002), while apotransferrin (aTf) cannot. As a consequence, we used pure cultured SC and submitted them to serum deprivation in order to promote dedifferentiation and evaluate the prodifferentiating ability of ferric ammonium citrate (FAC) through the expression of MBP, P0, p75NTR and c-myc. The levels of cAMP, CREB and p-CREB were also measured. Results show that Fe3+, either in its free form or as hTf, can prevent the dedifferentiation promoted by serum withdrawal. Both FAC and hTf were in turn proven to increase the levels of cAMP and CREB phosphorylation, as well as reactive oxygen species levels. This effect was inhibited by deferroxamine (an iron chelator), H9 (a cAMP-PKA antagonist) and N-acetylcysteine (a powerful antioxidant). Results described in the present manuscript demonstrate that iron promotes cAMP elevation, which might be the reason for the expression of myelin proteins essential for SC maturation.