Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans
- Background: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein ( hsp ) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity. Methods: We exposed wild type and selected hsp mutant worms to Mn (30 min) and next evaluated further the most susceptible strains. We analyzed survi val, protein carbonylation (as a marker of oxidative stress) and Parkinson ’ s disease related gene expression immediately after Mn exposure. Lastly, we observed dopaminergic neurons in wild type worms and in hsp-70 mutants following Mn treatment. Analysis of the data was performed by one-way or two way ANOVA, depending on the case, followed by post-hoc Bonferroni test if the overall p value was less than 0.05. Results: WeBackground: All living cells display a rapid molecular response to adverse environmental conditions, and the heat shock protein family reflects one such example. Hence, failing to activate heat shock proteins can impair the cellular response. In the present study, we evaluated whether the loss of different isoforms of heat shock protein ( hsp ) genes in Caenorhabditis elegans would affect their vulnerability to Manganese (Mn) toxicity. Methods: We exposed wild type and selected hsp mutant worms to Mn (30 min) and next evaluated further the most susceptible strains. We analyzed survi val, protein carbonylation (as a marker of oxidative stress) and Parkinson ’ s disease related gene expression immediately after Mn exposure. Lastly, we observed dopaminergic neurons in wild type worms and in hsp-70 mutants following Mn treatment. Analysis of the data was performed by one-way or two way ANOVA, depending on the case, followed by post-hoc Bonferroni test if the overall p value was less than 0.05. Results: We verified that the loss of hsp-70, hsp-3 and chn-1 increased the vulnerability to Mn, as exposed mutant worms showed lower survival rate and increased protein oxidation. The importance of hsp-70 against Mn toxicity was then corroborated in dopaminergic neurons, where Mn neurotoxicity was aggravated. The lack of hsp-70 also blocked the transcriptional upregulation of pink1 , a gene that has been linked to Parkinson ’ sdisease. Conclusions: Taken together, our data suggest that Mn exposu re modulates heat shock protein expression, particularly HSP-70, in C. elegans .Furthermore,lossof hsp-70 increases protein oxidation and dopaminergic neuronal degeneration following manganese exposure, which is associated with the inhibition of pink1 increased expression, thus pot entially exacerbating the v ulnerability to this metal.…
Author details: | Daiana Silva AvilaORCiD, Alexandre Benedetto, Catherine Au, Julia BornhorstORCiDGND, Michael A. Aschner |
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URN: | urn:nbn:de:kobv:517-opus4-407286 |
Title of parent work (English): | BMC pharmacology and toxicology |
Publication series (Volume number): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (439) |
Publication type: | Postprint |
Language: | English |
Date of first publication: | 2018/06/19 |
Publication year: | 2016 |
Publishing institution: | Universität Potsdam |
Release date: | 2018/06/19 |
Tag: | Caenorhabitis elegans; Manganese; heat shock proteins; hsp-70; pink1 |
Number of pages: | 9 |
Source: | BMC Pharmacology and Toxicology 17 (2016), DOI: 10.1186/s40360-016-0097-2 |
Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät |
Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft | |
DDC classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Peer review: | Referiert |
Publishing method: | Open Access |
Grantor: | BioMed Central |
License (German): | CC-BY - Namensnennung 4.0 International |