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Putrescine as indicator of manganese neurotoxicity: Dose-response study in human SH-SY5Y cells

Jolyn Fernandes1, Joshua D Chandler1, Ken H Liu1

  • 1Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Emory University, Atlanta, GA, 30322, USA.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association
|April 24, 2018
PubMed

Insights

Manganese exposure increases putrescine, a key molecule in polyamine metabolism, in neuronal cells. This finding may help assess manganese

Area of Science:

  • Neuroscience
  • Biochemistry
  • Toxicology

Background:

  • Disrupted polyamine metabolism, marked by elevated putrescine, is linked to neuronal dysfunction.
  • Excess manganese (Mn) causes neurotoxicity, but biochemical response assessment methods are limited.
  • Dose-response data on Mn effects on putrescine and polyamine metabolism are lacking.

Purpose of the Study:

  • To investigate the hypothesis that Mn exposure leads to putrescine accumulation in a neuronal cell line.
  • To explore dose-response effects of Mn on putrescine and related metabolites within non-toxic to toxic ranges.
  • To identify biochemical pathways affected by Mn-induced putrescine changes.

Main Methods:

  • Human SH-SY5Y neuroblastoma cells were treated with varying concentrations of MnCl2.
  • Metabolomic analysis using liquid chromatography-ultra high-resolution mass spectrometry.
  • Metabolome-wide association study (MWAS) to identify pathway correlations with putrescine.

Main Results:

  • Mn exposure caused a dose-dependent increase in putrescine levels across non-toxic to toxic concentrations.
  • MWAS revealed positive correlations between putrescine and N8-acetylspermidine, methionine, and urea cycle metabolites.
  • Putrescine showed negative correlations with gamma-aminobutyric acid (GABA) and succinate metabolites (P < 0.001, FDR < 0.01).

Conclusions:

  • Mn exposure induces putrescine accumulation in neuronal cells in a dose-dependent manner.
  • Putrescine and associated metabolite changes may serve as biomarkers for Mn effects.
  • These findings suggest potential for monitoring Mn intake effects within adequate to tolerable upper limit ranges.
Keywords:
Dietary recommended intakeIn vitro toxicity testingMetal nutritionNeurotoxicologyNutritional toxicology

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