TY  - JOUR
A1  - Nicolai, Merle Marie
A1  - Witt, Barbara
A1  - Friese, Sharleen
A1  - Michaelis, Vivien
A1  - Hölz-Armstrong, Lisa
A1  - Martin, Maximilian
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
A1  - Bornhorst, Julia
T1  - Mechanistic studies on the adverse effects of manganese overexposure in differentiated LUHMES cells
T2  - Food and chemical toxicology
N2  - Manganese (Mn) is an essential trace element, but overexposure is associated with toxicity and neurological dysfunction. Accumulation of Mn can be observed in dopamine-rich regions of the brain in vivo and Mn-induced oxidative stress has been discussed extensively. Nevertheless, Mn-induced DNA damage, adverse effects of DNA repair, and possible resulting consequences for the neurite network are not yet characterized. For this, LUHMES cells were used, as they differentiate into dopaminergic-like neurons and form extensive neurite networks. Experiments were conducted to analyze Mn bioavailability and cytotoxicity of MnCl2, indicating a dose-dependent uptake and substantial cytotoxic effects. DNA damage, analyzed by means of 8-oxo-7,8-dihydro-2'-guanine (8oxodG) and single DNA strand break formation, showed significant dose- and time-dependent increase of DNA damage upon 48 h Mn exposure. Furthermore, the DNA damage response was increased which was assessed by analytical quantification of poly(ADP-ribosyl)ation (PARylation). Gene expression of the respective DNA repair genes was not significantly affected. Degradation of the neuronal network is significantly altered by 48 h Mn exposure. Altogether, this study contributes to the characterization of Mn-induced neurotoxicity, by analyzing the adverse effects of Mn on genome integrity in dopaminergic-like neurons and respective outcomes.
KW  - Manganese
KW  - Dopaminergic neurons
KW  - DNA integrity
KW  - DNA repair
KW  - Neurodegeneration
KW  - Oxidative stress
KW  - Genotoxicity
Y1  - 2022
UR  - https://publishup.uni-potsdam.de/frontdoor/index/index/docId/62797
SN  - 0278-6915
SN  - 1873-6351
VL  - 161
PB  - Elsevier
CY  - Oxford
ER  -