Influence of Dopamine on Fluorescent Advanced Glycation End Products Formation Using Drosophila melanogaster

Biomolecules. 2021 Mar 17;11(3):453. doi: 10.3390/biom11030453.

Abstract

Non-enzymatic glycation and covalent modification of proteins leads to Advanced Glycation End products (AGEs). AGEs are biomarkers of aging and neurodegenerative disease, and can be induced by impaired neuronal signaling. The objective of this study was to investigate if manipulation of dopamine (DA) in vitro using the model protein, bovine serum albumin (BSA), and in vivo using the model organism Drosophila melanogaster, influences fluorescent AGEs (fAGEs) formation as an indicator of dopamine-induced oxidation events. DA inhibited fAGEs-BSA synthesis in vitro, suggesting an anti-oxidative effect, which was not observed when flies were fed DA. Feeding flies cocaine and methamphetamine led to increased fAGEs formation. Mutants lacking the dopaminergic transporter or the D1-type showed further elevation of fAGEs accumulation, indicating that the long-term perturbation in DA function leads to higher production of fAGEs. To confirm that DA has oxidative properties in vivo, we fed flies antioxidant quercetin (QUE) together with methamphetamine. QUE significantly decreased methamphetamine-induced fAGEs formation suggesting that the perturbation of DA function in vivo leads to increased oxidation. These findings present arguments for the use of fAGEs as a biomarker of DA-associated neurodegenerative changes and for assessment of antioxidant interventions such as QUE treatment.

Keywords: Drosophila melanogaster; dopamine (DA); fluorescent advanced glycation end products (fAGEs); oxidation; psychostimulants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antioxidants / administration & dosage
  • Antioxidants / pharmacology
  • Cattle
  • Dopamine / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Glycation End Products, Advanced / metabolism*
  • Glycosylation
  • Male
  • Mutation
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism
  • Oxidation-Reduction
  • Oxidative Stress / drug effects
  • Quercetin / administration & dosage
  • Quercetin / pharmacology
  • Serum Albumin, Bovine / metabolism*
  • Spectrometry, Fluorescence

Substances

  • Antioxidants
  • Glycation End Products, Advanced
  • Serum Albumin, Bovine
  • Quercetin
  • Dopamine