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

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.

A Proteomic Analysis Provides Novel Insights into the Stress Responses of Caenorhabditis elegans towards Nematicidal Cry6A Toxin from Bacillus thuringiensis

“…Living cells upon confronting adverse environmental stimulator, physiological stressor and even bacterial infection, can exert a rapid molecular response to promote cell adaptation for survival. HSP family represents one such example 38 . HSPs are highly evolutionarily conserved molecular chaperones, which are ubiquitously found in subcellular compartments, cells, tissues, and give immediate responses during any stress, tissue damage, or bacterial infection 39 , 40 .…”

C. elegans as a model in developmental neurotoxicology

“…Several studies from our lab and others have shown that C. elegans treatment with Mn at early life (Larva-1 stage, L1) induces DAergic neurodegeneration in L1, L4 and young adults (Settivari et al , 2009; Benedetto et al , 2010; Settivari et al , 2013; Leyva-Illades et al , 2014; Avila et al , 2016; Ijomone et al , 2016). Additionally, treatment of L1 worms with Mn altered neurobehavioral parameters at a later stage.…”

“…Similarly to higher organisms, in worms Mn has been reported to trigger reactive oxygen species (ROS) generation and induced oxidative stress (Settivari et al , 2009; Benedetto et al , 2010; Settivari et al , 2013; Avila et al , 2016), as well as alter activities of apoptotic proteins (Settivari et al , 2013) and PD-associated genes (Chen et al , 2015b). Expression of GST-1 (glutathione transferase 1) and SKN-1, a homologue of human nuclear factor (erythroid-derived 2)-like 2, NRF-2 – a transcription factor regulating antioxidant response involved in antioxidant and detoxification enzymes regulation, has been shown to inhibit Mn-induced developmental neurotoxicity in C. elegans (Settivari et al , 2009; Benedetto et al , 2010; Settivari et al , 2013).…”

Toxic Effects of Bisphenol A, Propyl Paraben, and Triclosan on Caenorhabditis elegans

“…However, once ROS levels pass the required threshold, the defense against oxidative stress decreases, leading to toxicity. The activation of hsp-70 transcription suggests protection against protein oxidation and neuronal damage [ 117 ], which suggests that these chemicals play a role in oxidative damage.…”