TY  - GEN
A1  - Avila, Daiana Silva
A1  - Benedetto, Alexandre
A1  - Au, Catherine
A1  - Bornhorst, Julia
A1  - Aschner, Michael A.
T1  - Involvement of heat shock proteins on Mn-induced toxicity in Caenorhabditis elegans
T2  - BMC pharmacology and toxicology
N2  - 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.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 439 
KW  - Caenorhabitis elegans
KW  - Manganese
KW  - heat shock proteins
KW  - hsp-70
KW  - pink1
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-407286
ER  - 
TY  - GEN
A1  - Henze, Andrea
A1  - Homann, Thomas
A1  - Rohn, Isabelle
A1  - Aschner, Michael A.
A1  - Link, Christopher D.
A1  - Kleuser, Burkhard
A1  - Schweigert, Florian J.
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
T1  - Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin
N2  - The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization – time of flight – mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 312 
KW  - binding
KW  - c. elegans
KW  - cells
KW  - disease
KW  - force-field
KW  - life-span
KW  - menadione
KW  - n-acetyl-cysteine
KW  - protein
KW  - s-glutathionylation
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-103674
ER  -