TY  - JOUR
A1  - Michaelis, Vivien
A1  - Aengenheister, Leonie
A1  - Tuchtenhagen, Max
A1  - Rinklebe, Jörg
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
A1  - Buerki-Thurnherr, Tina
A1  - Bornhorst, Julia
T1  - Differences and interactions in placental manganese and iron transfer across an in vitro model of human villous trophoblasts
JF  - International journal of molecular sciences
N2  - Manganese (Mn) as well as iron (Fe) are essential trace elements (TE) important for the maintenance of physiological functions including fetal development. However, in the case of Mn, evidence suggests that excess levels of intrauterine Mn are associated with adverse pregnancy outcomes. Although Mn is known to cross the placenta, the fundamentals of Mn transfer kinetics and mechanisms are largely unknown. Moreover, exposure to combinations of TEs should be considered in mechanistic transfer studies, in particular for TEs expected to share similar transfer pathways. Here, we performed a mechanistic in vitro study on the placental transfer of Mn across a BeWo b30 trophoblast layer. Our data revealed distinct differences in the placental transfer of Mn and Fe. While placental permeability to Fe showed a clear inverse dose-dependency, Mn transfer was largely independent of the applied doses. Concurrent exposure of Mn and Fe revealed transfer interactions of Fe and Mn, indicating that they share common transfer mechanisms. In general, mRNA and protein expression of discussed transporters like DMT1, TfR, or FPN were only marginally altered in BeWo cells despite the different exposure scenarios highlighting that Mn transfer across the trophoblast layer likely involves a combination of active and passive transport processes.
KW  - manganese
KW  - iron
KW  - placental transfer
KW  - TE interactions
KW  - BeWo b30
KW  - trophoblasts
Y1  - 2022
U6  - https://doi.org/10.3390/ijms23063296
SN  - 1422-0067
VL  - 23
IS  - 6
PB  - MDPI
CY  - Basel
ER  - 
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
JF  - 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
U6  - https://doi.org/10.1016/j.fct.2022.112822
SN  - 0278-6915
SN  - 1873-6351
VL  - 161
PB  - Elsevier
CY  - Oxford
ER  -