Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegansReportar como inadecuado




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BMC Pharmacology and Toxicology

, 17:54

ToxicologyNeurometals

Abstract

BackgroundAll 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.

MethodsWe 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.

ResultsWe 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.

ConclusionsTaken 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.

KeywordsCaenorhabitis elegans Manganese Heat shock proteins hsp-70 pink1 AbbreviationsCHIPC-terminus of Hsc70 interacting protein

DAdopamine

DATdopamine transporter

DNPHdinitrophenylhydrazine

DTTdithiothreitol

GFPgreen fluorescent protein

HSFheat shock factor

HSPheat shock protein

IgGImmunoglobulin G

Mnmanganese

MPTP1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

PDParkinson’s Disease

Pink1PTEN-induced kinase 1

WTwildtype

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Autor: Daiana Silva Avila - Alexandre Benedetto - Catherine Au - Julia Bornhorst - Michael Aschner

Fuente: https://link.springer.com/







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