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Updated: Jan 19, 2026
Combined Nucleotide and Protein Extractions in Caenorhabditis elegans
Published on: March 17, 2019
The role of poly(ADP-ribose) polymerases in manganese exposed Caenorhabditis elegans
Catherine Neumann1, Jessica Baesler2, Gereon Steffen1
1Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.
Background And Aim:
When exceeding the homeostatic range, manganese (Mn) might cause neurotoxicity, characteristic of the pathophysiology of several neurological diseases. Although the underlying mechanism of its neurotoxicity remains unclear, Mn-induced oxidative stress contributes to disease etiology. DNA damage caused by oxidative stress may further trigger dysregulation of DNA-damage-induced poly(ADP-ribosyl)ation (PARylation), which is of central importance especially for neuronal homeostasis. Accordingly, this study was designed to assess in the genetically traceable in vivo model Caenorhabditis elegans the role of PARylation as well as the consequences of loss of pme-1 or pme-2 (orthologues of PARP1 and PARP2) in Mn-induced toxicity.
Methods:
A specific and sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed to quantify PARylation in worms. Next to monitoring the PAR level, pme-1 and pme-2 gene expression as well as Mn-induced oxidative stress was studied in wildtype worms and the pme deletion mutants.
Results And Conclusion:
While Mn failed to induce PARylation in wildtype worms, toxic doses of Mn led to PAR-induction in pme-1-deficient worms, due to an increased gene expression of pme-2 in the pme-1 deletion mutants. However, this effect could not be observed at sub-toxic Mn doses as well as upon longer incubation times. Regarding Mn-induced oxidative stress, the deletion mutants did not show hypersensitivity. Taken together, this study characterizes worms to model PAR inhibition and addresses the consequences for Mn-induced oxidative stress in genetically manipulated worms.
Insights
Manganese (Mn) exposure can cause neurotoxicity, but its effects on poly(ADP-ribosyl)ation (PARylation) and oxidative stress were unclear. This study found Mn induced PARylation in pme-1 deficient worms, suggesting a role for PARylation in Mn toxicity.
Area of Science:
- Neuroscience
- Toxicology
- Genetics
Background:
- Manganese (Mn) exposure can lead to neurotoxicity, contributing to neurological disease pathophysiology.
- The precise mechanisms of Mn neurotoxicity are not fully understood, but Mn-induced oxidative stress is implicated.
- Oxidative stress-induced DNA damage may disrupt poly(ADP-ribosyl)ation (PARylation), crucial for neuronal homeostasis.
Purpose of the Study:
- To investigate the role of PARylation in manganese-induced toxicity.
- To assess the consequences of impaired PARylation (loss of pme-1 or pme-2) on Mn toxicity.
- To utilize the genetically traceable Caenorhabditis elegans model for in vivo studies.
Main Methods:
- Developed a sensitive isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify PARylation in C. elegans.
- Monitored PARylation levels, pme-1 and pme-2 gene expression, and Mn-induced oxidative stress.
- Compared wildtype worms with pme deletion mutants under Mn exposure.
Main Results:
- Manganese did not induce PARylation in wildtype worms.
- Toxic Mn doses induced PARylation in pme-1 deficient worms, linked to increased pme-2 expression.
- This PARylation induction was not observed at sub-toxic Mn doses or prolonged incubation.
- Deletion mutants did not exhibit hypersensitivity to Mn-induced oxidative stress.
Conclusions:
- C. elegans can serve as a model to study PARylation inhibition in the context of Mn toxicity.
- PARylation plays a role in Mn-induced toxicity, particularly in the absence of functional PME-1.
- The study clarifies the interplay between Mn exposure, PARylation, and oxidative stress in a genetic model.
