Differential Gene Expression in Differentiated Human Neuroblastoma SH-SY5Y Cells in Response to a Cocktail of

Prakshit Niraula1, Rachel A Page1, Barry R Palmer1

  • 1School of Health Sciences, Massey University, Wellington 6021, New Zealand.

Insights

Tobacco smoke components, not MAO gene expression changes, alter gene expression in neuroblastoma cells. MAO inhibition by tobacco may link smoking to addiction and disease.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Genomics

Background:

  • Tobacco smoke contains nicotine and monoamine oxidase inhibitors (MAOIs).
  • MAOIs in tobacco smoke reduce monoamine oxidase (MAO) activity.
  • The impact of MAO inhibition on gene expression in neuronal cells is not fully understood.

Purpose of the Study:

  • To investigate the effects of nicotine, tobacco smoke preparation (TPM), and MAOIs on MAO gene expression and global gene expression in differentiated human neuroblastoma (SH-SY5Y) cells.
  • To determine if changes in MAO gene expression correlate with reduced MAO activity observed after tobacco smoke exposure.

Main Methods:

  • Differentiated SH-SY5Y cells were exposed to nicotine, TPM, or an MAOI cocktail for 3 days.
  • MAO activity was measured to confirm inhibition.
  • Quantitative PCR (qPCR) and mRNA sequencing were used to analyze MAO gene expression and global gene expression changes.

Main Results:

  • MAO activity was reduced by approximately 50% in cells exposed to TPM and the MAOI cocktail.
  • No significant changes in MAOA and MAOB gene expression were observed with any treatment.
  • MAOI cocktail exposure led to differential expression of 23 genes, many linked to smoking-related diseases and addiction.
  • Nicotine and TPM exposure also resulted in distinct sets of gene expression changes.

Conclusions:

  • Reduced MAO activity in response to tobacco smoke components is not mediated by changes in MAO gene expression.
  • The observed gene expression alterations, particularly those induced by MAOIs, suggest a role for MAO inhibition in mediating smoking-related diseases and addiction.