PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells

Nicoletta Marchesi, Marialaura Amadio, Claudia Colombrita, Stefano Govoni, Antonia Ratti, Alessia Pascale

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

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 α-secretase involved in the non-amyloidogenic processing of the amyloid-β protein precursor (AβPP) which leads to the production of the neuroprotective sAβPPα 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 nELAV and ADAM10 protein contents; similar results were obtained by Aβ40 treatment in wild-type SH-SY5Y cells. In HuD-silenced cells, the exposure to Bryostatin-1 counteracted both nELAV and ADAM10 proteins downregulation, by restoring nELAV/ADAM10 basal levels. We also found that sAβPPα release, which seemed not to be compromised by Aβ40 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.

Original languageEnglish
Pages (from-to)535-547
Number of pages13
JournalJournal of Alzheimer's Disease
Volume54
Issue number2
DOIs
Publication statusPublished - Sep 6 2016

Fingerprint

ELAV Proteins
Neuroblastoma
Amyloid Precursor Protein Secretases
RNA-Binding Proteins
Uracil
Amyloid beta-Protein Precursor
Gene Silencing
Adenine
Neurodegenerative Diseases
Down-Regulation
Gene Expression
Messenger RNA
Peptides
bryostatin 1
ADAM10 Protein

Keywords

  • ADAM10
  • amyloid-β
  • Bryostatin-1
  • HuD silencing
  • nELAV
  • sAβPPα

ASJC Scopus subject areas

  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

Cite this

PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells. / Marchesi, Nicoletta; Amadio, Marialaura; Colombrita, Claudia; Govoni, Stefano; Ratti, Antonia; Pascale, Alessia.

In: Journal of Alzheimer's Disease, Vol. 54, No. 2, 06.09.2016, p. 535-547.

Research output: Contribution to journalArticle

Marchesi, N, Amadio, M, Colombrita, C, Govoni, S, Ratti, A & Pascale, A 2016, 'PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells', Journal of Alzheimer's Disease, vol. 54, no. 2, pp. 535-547. https://doi.org/10.3233/JAD-160299
Marchesi, Nicoletta ; Amadio, Marialaura ; Colombrita, Claudia ; Govoni, Stefano ; Ratti, Antonia ; Pascale, Alessia. / PKC Activation Counteracts ADAM10 Deficit in HuD-Silenced Neuroblastoma Cells. In: Journal of Alzheimer's Disease. 2016 ; Vol. 54, No. 2. pp. 535-547.
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