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Keywords
- Caenorhabitis elegans (1)
- Manganese (1)
- heat shock proteins (1)
- hsp-70 (1)
- pink1 (1)
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:
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.