Nutritive Manganese and Zinc Overdosing in Aging C. elegans Result in a Metallothionein-Mediated Alteration in Metal Homeostasis.

Abstract

SCOPE:

Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration.

METHODS AND RESULTS:

Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration.

CONCLUSIONS:

A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.

• Authors: Jessica Baesler, Vivien Michaelis, Michael Stiboller, Hajo Haase, Michael Aschner, Tanja Schwerdtle, Stephen R Sturzenbaum, Julia Bornhorst
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 8 Pg. e2001176 (04 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 33641237 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Molecular Nutrition & Food Research published by Wiley-VCH GmbH.

Chemical References

• Caenorhabditis elegans Proteins
• MTL-1 protein, C elegans
• Manganese
• Metallothionein
• Ubiquitin-Protein Ligases
• parkin protein
• Zinc

Topics

• Aging (drug effects, physiology)
• Animals
• Animals, Genetically Modified
• Biological Availability
• Caenorhabditis elegans (drug effects, physiology)
• Caenorhabditis elegans Proteins (genetics, metabolism)
• Dopaminergic Neurons (drug effects, pathology)
• Drug Overdose (metabolism)
• Homeostasis (drug effects, genetics)
• Manganese (administration & dosage, adverse effects, pharmacokinetics)
• Metallothionein (genetics, metabolism)
• Mutation
• Toxicity Tests, Chronic
• Ubiquitin-Protein Ligases (genetics)
• Zinc (administration & dosage, adverse effects, pharmacokinetics)