Acrylamide alters CREB and retinoic acid signalling pathways during differentiation of the human neuroblastoma SH-SY5Y cell line

Kristina Attoff, Ylva Johansson, Andrea Cediel-Ulloa, Jessica Lundqvist, Rajinder Gupta, Florian Caiment, Anda Gliga, Anna Forsby*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Acrylamide (ACR) is a known neurotoxicant which crosses the blood-brain barrier, passes the placenta and has been detected in breast milk. Hence, early-life exposure to ACR could lead to developmental neurotoxicity. The aim of this study was to elucidate if non-cytotoxic concentrations of ACR alter neuronal differentiation by studying gene expression of markers significant for neurodevelopment in the human neuroblastoma SH-SY5Y cell model. Firstly, by using RNASeq we identified two relevant pathways that are activated during 9 days of retinoic acid (RA) induced differentiation i.e. RA receptor (RAR) activation and the cAMP response element-binding protein (CREB) signalling pathways. Next, by qPCR we showed that 1 and 70 mu M ACR after 9 days exposure alter the expression of 13 out of 36 genes in the RAR activation pathway and 18 out of 47 in the CREB signalling pathway. Furthermore, the expression of established neuronal markers i.e. BDNF, STXBP2, STX3, TGFB1 and CHAT were down-regulated. Decreased protein expression of BDNF and altered ratio of phosphorylated CREB to total CREB were confirmed by western blot. Our results reveal that micromolar concentrations of ACR sustain proliferation, decrease neurite outgrowth and interfere with signalling pathways involved in neuronal differentiation in the SH-SY5Y cell model.

Original languageEnglish
Article number16714
Number of pages15
JournalScientific Reports
Volume10
Issue number1
DOIs
Publication statusPublished - 7 Oct 2020

Keywords

  • FAMILY TRANSCRIPTION FACTOR
  • DEVELOPMENTAL NEUROTOXICITY
  • PROTEOMIC ANALYSIS
  • BINDING PROTEIN
  • EXPRESSION
  • INCREASES
  • EXPOSURE
  • GENES
  • BIOSYNTHESIS
  • METABOLISM

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