No 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

Intracellular redox state modulation can influence cell proliferation, differentiation or death. Here we show that Retinoic Acid (RA)‐induced neuroblastoma cell differentiation is accompanied by increased expression of anion superoxide generating enzyme NADPH oxidase, decreased SOD1 expression and increased catalase expression. Moreover, cell differentiation induced PKC alfa inactivation and PKC delta activation. We believe these alterations responsible for the observed cell sensitivity to glycoxidative stress: indeed, only the RA‐differentiated cell viability decreased after exposure to Advanced Glycation End Products (AGEs), via intracellular ROS overproduction, while undifferentiated cells proved insensitive. AGE‐induced effects on differentiated cells were prevented by pre‐treating cells with NADPH oxidase or PKC delta inhibitors. These observations may be useful in order to identify redox sensitive molecular targets responsible for cell growing rate modifications.Grants from PRIN n.2006065711_002