Zn homeostasis in genetic models of Parkinson's disease in Caenorhabditis elegans

Jessica Baesler, Johannes F. Kopp, Gabriele Pohl, Michael Aschner, Hajo Haase, Tanja Schwerdtle, Julia Bornhorst

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

While the underlying mechanisms of Parkinson's disease (PD) are still insufficiently studied, a complex interaction between genetic and environmental factors is emphasized. Nevertheless, the role of the essential trace element zinc (Zn) in this regard remains controversial. In this study we altered Zn balance within PD models of the versatile model organism Caenorhabditis elegans (C. elegans) in order to examine whether a genetic predisposition in selected genes with relevance for PD affects Zn homeostasis. Protein-bound and labile Zn species act in various areas, such as enzymatic catalysis, protein stabilization pathways and cell signaling. Therefore, total Zn and labile Zn were quantitatively determined in living nematodes as individual biomarkers of Zn uptake and bioavailability with inductively coupled plasma tandem mass spectrometry (ICP-MS/MS) or a multi-well method using the fluorescent probe ZinPyr-1. Young and middle-aged deletion mutants of catp-6 and pdr-1, which are orthologues of mammalian ATP13A2 (PARK9) and parkin (PARK2), showed altered Zn homeostasis following Zn exposure compared to wildtype worms. Furthermore, age-specific differences in Zn uptake were observed in wildtype worms for total as well as labile Zn species. These data emphasize the importance of differentiation between Zn species as meaningful biomarkers of Zn uptake as well as the need for further studies investigating the role of dysregulated Zn homeostasis in the etiology of PD.

Original languageEnglish (US)
Pages (from-to)44-49
Number of pages6
JournalJournal of Trace Elements in Medicine and Biology
Volume55
DOIs
StatePublished - Sep 2019

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Keywords

  • Caenorhabditis elegans
  • Labile zinc
  • Parkinson disease
  • Zinc
  • Zinc homeostasis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Inorganic Chemistry

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