Serum proteomic profiling of patients with amphetamine use disorder

Drug Alcohol Depend. 2020 Sep 1:214:108157. doi: 10.1016/j.drugalcdep.2020.108157. Epub 2020 Jul 2.

Abstract

Background: Amphetamine use disorder has been recently classified as an epidemic condition. Amphetamine use/abuse has been associated with several neurological and inflammatory effects. However, the exact mechanism involved in these effects warrants further investigation. The aim of this study was to determine any alterations in the serum proteome of individuals classified as patients with amphetamine use disorder compared to that of control subjects.

Methods: An untargeted proteomic approach employing two-dimensional difference in gel electrophoresis coupled with mass spectrometry was used to identify the patterns of differentially expressed proteins. Serum samples were collected from 20 individuals (males) including 10 subjects with amphetamine use disorder and 10 healthy controls for the present study.

Results: The analysis revealed 78 proteins with a significant difference in protein abundance between the amphetamine-addicted subjects and controls. Among them, 71 proteins were upregulated while 7 proteins remained downregulated in the amphetamine-addicted group. These proteins were further analyzed by ingenuity pathway analysis (IPA) to investigate their correlation with other biomarkers. IPA revealed the correlation of altered proteins with mitogen-activated protein kinase (MAP2K1/K2), p38MAPK, protein kinase-B (PKB; Akt), extracellular signal-regulated kinase (ERK1/2), and nuclear factor-κB signaling pathways. Importantly, these pathways are highly involved in neurological diseases, inflammatory responses, and cellular compromise.

Conclusions: Our data suggest that the changes in the levels of serum proteins between amphetamine and control groups might affect cellular compromise, inflammatory response, and neurological diseases.

Keywords: Amphetamine use disorder; Cellular compromise; Inflammation; Neurological diseases; Proteomics; Serum proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Amphetamine*
  • Biomarkers
  • Down-Regulation
  • Female
  • Gene Expression Profiling
  • Humans
  • MAP Kinase Kinase 1
  • Male
  • Mass Spectrometry
  • Proteome / analysis
  • Proteome / metabolism*
  • Proteomics / methods
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Substance-Related Disorders / blood*
  • Up-Regulation

Substances

  • Biomarkers
  • Proteome
  • Amphetamine
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human