PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells

Neuronal ELAV/Hu (nELAV) are RNA-binding proteins that mainly regulate gene expression by increasing the stability and/or translation rate of target mRNAs bearing ARE (adenine and uracil-rich elements) sequences. Among nELAV target transcripts there is ADAM10, an -secretase involved in the non-amyloidogenic processing of the amyloid- protein precursor (APP) which leads to the production of the neuroprotective sAPP peptide. The aim of this study was to evaluate if nELAV depletion affects ADAM10 expression in human SH-SY5Y neuroblastoma cells. We also studied the effects of Bryostatin-1, a molecule able to activate nELAV protein cascade. The specific HuD/nELAV gene silencing decreased both nELAVandADAM10 protein contents; similar results were obtained byA40 treatment in wild-type SH-SY5Y cells. In HuDsilenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels.We also found that sAPP release, which seemed not to be compromised by A40 challenge or HuD-silencing, was favored by Bryostatin-1. Overall, these findings strongly suggest that a deficiency in nELAV content negatively affects ADAM10 expression and may play a role in neurodegenerative diseases, which may benefit by molecules activating ELAV cascade.