TY  - GEN
A1  - Chen, Pan
A1  - Bornhorst, Julia
A1  - Aschner, Michael A.
T1  - Manganese metabolism in humans
T2  - Postprints der Universität Potsdam Mathematisch-Naturwissenschaftliche Reihe
N2  - Manganese (Mn) is an essential nutrient for intracellular activities; it functions as a cofactor for a variety of enzymes, including arginase, glutamine synthetase (GS), pyruvate carboxylase and Mn superoxide dismutase (Mn-SOD). Through these metalloproteins, Mn plays critically important roles in development, digestion, reproduction, antioxidant defense, energy production, immune response and regulation of neuronal activities. Mn deficiency is rare. In contrast Mn poisoning may be encountered upon overexposure to this metal. Excessive Mn tends to accumulate in the liver, pancreas, bone, kidney and brain, with the latter being the major target of Mn intoxication. Hepatic cirrhosis, polycythemia, hypermanganesemia, dystonia and Parkinsonism-like symptoms have been reported in patients with Mn poisoning. In recent years, Mn has come to the forefront of environmental concerns due to its neurotoxicity. Molecular mechanisms of Mn toxicity include oxidative stress, mitochondrial dysfunction, protein misfolding, endoplasmic reticulum (ER) stress, autophagy dysregulation, apoptosis, and disruption of other metal homeostasis. The mechanisms of Mn homeostasis are not fully understood. Here, we will address recent progress in Mn absorption, distribution and elimination across different tissues, as well as the intracellular regulation of Mn homeostasis in cells. We will conclude with recommendations for future research areas on Mn metabolism.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 711 
KW  - Manganese
KW  - Metal Metabolism
KW  - Homeostasis
KW  - Blood-Brain Barrier
KW  - Neurotoxicity
KW  - Transporters
KW  - Review
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-427432
SN  - 1866-8372
IS  - 711
ER  - 
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  -