Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans.
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.



We exposed wild type and selected hsp mutant worms to Mn (30 min) and next evaluated further the most susceptible strains. We analyzed survival, 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.



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's disease.



Taken together, our data suggest that Mn exposure modulates heat shock protein expression, particularly HSP-70, in C. elegans. Furthermore, loss of hsp-70 increases protein oxidation and dopaminergic neuronal degeneration following manganese exposure, which is associated with the inhibition of pink1 increased expression, thus potentially exacerbating the vulnerability to this metal.
Federal Pampa University, Uruguaiana, RS, Brazil.
Daiana Silva
DS
Avila
Faculty of Health and Medicine, Division of Biomedical and Life Sciences, Lancaster University, Lancaster, UK.
Alexandre
A
Benedetto
Institute of Healthy Ageing, and Department of Genetics, Evolution and Environment, University College London, London, UK.
Catherine
C
Au
Department of Food Chemistry, Institute of Nutritional Science, University of Potsdam, Potsdam, Germany.
Julia
J
Bornhorst
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Forchheimer 209, 1300 Morris Park Avenue, Bronx, NY, 10461, USA. michael.Aschner@einstein.yu.edu.|Center for Molecular Toxicology, and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University School of Medicine, Nashville, TN, USA. michael.Aschner@einstein.yu.edu.
Michael
M
Aschner
D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D006360:Heat-Shock Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D008345:Manganese / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; D008345:Manganese
Caenorhabitis elegans; Heat shock proteins; Manganese; hsp-70; pink1