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Archives of Toxicology

, Volume 92, Issue 1, pp 289–299 | Cite as

Oxidative inactivation of the endogenous antioxidant protein DJ-1 by the food contaminants 3-MCPD and 2-MCPD

  • Thorsten Buhrke
  • Linn Voss
  • Anja Briese
  • Heike Stephanowitz
  • Eberhard Krause
  • Albert Braeuning
  • Alfonso Lampen
Molecular Toxicology

Abstract

3-Chloro-1,2-propanediol (3-MCPD) and 2-chloro-1,3-propanediol (2-MCPD) are heat-induced food contaminants being present either as free substances or as fatty acid esters in numerous foods. 3-MCPD was classified to be possibly carcinogenic to humans (category 2B) with kidney and testis being the primary target organs according to animal studies. A previous 28-day oral feeding study with rats revealed that the endogenous antioxidant protein DJ-1 was strongly deregulated at the protein level in kidney, liver, and testis of the experimental animals that had been treated either with 3-MCPD, 2-MCPD or their dipalmitate esters. Here we show that this deregulation is due to the oxidation of a conserved, redox-active cysteine residue (Cys106) of DJ-1 to a cysteine sulfonic acid which is equivalent to loss of function of DJ-1. Irreversible oxidation of DJ-1 is associated with a number of oxidative stress-related diseases such as Parkinson, cancer, and type II diabetes. It is assumed that 3-MCPD or 2-MCPD do not directly oxidize DJ-1, but that these substances induce the formation of reactive oxygen species (ROS) which in turn trigger DJ-1 oxidation. The implications of 3-MCPD/2-MCPD-mediated ROS formation in vivo for the ongoing risk assessment of these compounds as well as the potential of oxidized DJ-1 to serve as a novel effect biomarker for 3-MCPD/2-MCPD toxicity are being discussed.

Keywords

2-MCPD 3-MCPD Cysteine oxidation DJ-1 Oxidative stress 

Notes

Acknowledgements

We thank Christine Meckert and Linda Brandenburger for technical assistance. This work was funded by the German Federal Institute for Risk Assessment (Project 1322-523).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Thorsten Buhrke
    • 1
  • Linn Voss
    • 1
  • Anja Briese
    • 1
  • Heike Stephanowitz
    • 2
  • Eberhard Krause
    • 2
  • Albert Braeuning
    • 1
  • Alfonso Lampen
    • 1
  1. 1.Department of Food SafetyGerman Federal Institute for Risk AssessmentBerlinGermany
  2. 2.Mass Spectrometry GroupLeibniz-Institut für Molekulare PharmakologieBerlinGermany

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