The role of poly(ADP-ribose) polymerases in manganese exposed Caenorhabditis elegans
Autor: | Julia Bornhorst, Michael Aschner, Catherine Neumann, Gereon Steffen, Tanja Schwerdtle, Aswin Mangerich, Tabea Zubel, Jessica Baesler, Alexander Bürkle, Merle M. Nicolai |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
DNA damage
Poly ADP ribose polymerase 010501 environmental sciences medicine.disease_cause 01 natural sciences Biochemistry Article Inorganic Chemistry 03 medical and health sciences 0302 clinical medicine PARP1 Tandem Mass Spectrometry ddc:570 Gene expression medicine Animals Caenorhabditis elegans Caenorhabditis elegans Proteins 0105 earth and related environmental sciences Manganese biology Chemistry Wild type Neurotoxicity biology.organism_classification medicine.disease Glutathione Cell biology Manganese Caenorhabditis elegans oxidative stress DNA damage response poly(ADP-ribosyl)ation Molecular Medicine Poly(ADP-ribose) Polymerases 030217 neurology & neurosurgery Oxidative stress Chromatography Liquid |
Zdroj: | J Trace Elem Med Biol |
Popis: | Background and AimWhen 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.MethodsA 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 ConclusionWhile 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. published |
Databáze: | OpenAIRE |
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