Title: Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans.
Authors: Avila, Daiana Silva; Benedetto, Alexandre; Au, Catherine; Bornhorst, Julia; Aschner, Michael
Published In BMC Pharmacol Toxicol, (2016 11 02)
Abstract: 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.
PubMed ID: 27802836
MeSH Terms: Animals; Animals, Genetically Modified; Caenorhabditis elegans; Caenorhabditis elegans Proteins/antagonists & inhibitors; Caenorhabditis elegans Proteins/biosynthesis*; Caenorhabditis elegans Proteins/genetics; Dose-Response Relationship, Drug; Heat-Shock Proteins/antagonists & inhibitors; Heat-Shock Proteins/biosynthesis*; Heat-Shock Proteins/genetics; Manganese/toxicity*; Oxidative Stress/drug effects; Oxidative Stress/physiology