Publication: DELETION OF DIVALENT METAL TRANSPORTER HOMOLOGS IN Caenorhabditis elegans PREVENTS LANTHANUM- AND YTTERBIUM-INDUCED OXIDATIVE INJURY
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Date
2025-04-17
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Abstract
Lanthanide series elements are transition metals that are used in a variety of electronics, including superconductors, electronic polishers, hybrid car components, and rechargeable batteries, as well as in fertilizers, antimicrobials, contrast agents for medical imaging and diesel fuel additives. Levels of lanthanides have risen significantly in both industrial areas and environmentally. While we are starting to recognize health effects of lanthanide exposure, it is currently unknown how lanthanide metals enter cells. If we are to understand their toxicokinetics in the human body, it is imperative to determine mechanisms by which lanthanides are distributed. We hypothesized that endogenous divalent metal transporters (DMTs) are responsible for lanthanide entry into cells, and that genetic ablation of DMT transporters in Caenorhabditis elegans would protect the worms from lanthanide-induced toxicity. In this study, we treated wild type N2 or transgenic worms that lacked DMT homologs smf-1, smf-2, or smf-3, with increasing concentrations of La or ytterbium (Yb). Knock out of either of the smf genes shifted the dose-response curve for La or Yb to the right of the N2 dose-response curve, signifying protection from the mutations. We have previously observed that La and Yb cause increased body burden of oxidative stress in worms. Treatment of the smf mutant worms with La or Yb caused significantly less reactive oxygen species (ROS) generated in the worm as compared to N2 worms. Glutathione levels have been shown to decrease in N2 worms following La or Yb treatment, however GSH levels were rescued by deletion of the smf genes. Furthermore, smf mutants showed less mitochondrial damage and had increased levels of ATP as compared to N2. These results suggest that DMTs are important mediators for lanthanide series elements to enter eukaryotic cells.