Retinoic acid‐induced neuroblastoma differentiation is dependent from NOX activation

Abstract

NOX is a multimeric enzyme able to generate superoxide anion as main reaction product. The wide distribution of NOX isoforms in many tissues and cells underlies the role of superoxide anion and reactive oxygen species in cell pathophysiology. In this work, we found that in SH‐SY5Y neuroblastoma cells treated up to 7 days with 10microM retinoic acid (RA) cell differentiation, monitored by cell count, MAP2 expression increase and morphological changes, was accompanied by the up‐regulation of NOX activity, as revealed by regulatory subunit translocation and the overproduction of superoxide anion. Moreover, PKC delta protein level was increased by RA and was involved in NOX activation and in MAP2 induction as shown using siRNA tools.We suppose NOX involvement in cytoskeleton remodelling during cell differentiation, since the enzyme activity inhibition obtained with DPI exerted a strong preventing effect on cell morphological changes induced by RA. NOX silencing strategy will be applied to confirm these findings.Grants form Genoa University and MIUR‐PRIN 20077S9A32_002