TY  - JOUR
A1  - Winkelbeiner, Nicola Lisa
A1  - Wandt, Viktoria Klara Veronika
A1  - Ebert, Franziska
A1  - Lossow, Kristina
A1  - Bankoglu, Ezgi E.
A1  - Martin, Maximilian
A1  - Mangerich, Aswin
A1  - Stopper, Helga
A1  - Bornhorst, Julia
A1  - Kipp, Anna Patricia
A1  - Schwerdtle, Tanja
T1  - A Multi-Endpoint Approach to Base Excision Repair Incision Activity Augmented by PARylation and DNA Damage Levels in Mice
BT  - Impact of Sex and Age
JF  - International Journal of Molecular Sciences
N2  - Investigation of processes that contribute to the maintenance of genomic stability is one crucial factor in the attempt to understand mechanisms that facilitate ageing. The DNA damage response (DDR) and DNA repair mechanisms are crucial to safeguard the integrity of DNA and to prevent accumulation of persistent DNA damage. Among them, base excision repair (BER) plays a decisive role. BER is the major repair pathway for small oxidative base modifications and apurinic/apyrimidinic (AP) sites. We established a highly sensitive non-radioactive assay to measure BER incision activity in murine liver samples. Incision activity can be assessed towards the three DNA lesions 8-oxo-2’-deoxyguanosine (8-oxodG), 5-hydroxy-2’-deoxyuracil (5-OHdU), and an AP site analogue. We applied the established assay to murine livers of adult and old mice of both sexes. Furthermore, poly(ADP-ribosyl)ation (PARylation) was assessed, which is an important determinant in DDR and BER. Additionally, DNA damage levels were measured to examine the overall damage levels. No impact of ageing on the investigated endpoints in liver tissue were found. However, animal sex seems to be a significant impact factor, as evident by sex-dependent alterations in all endpoints investigated. Moreover, our results revealed interrelationships between the investigated endpoints indicative for the synergetic mode of action of the cellular DNA integrity maintaining machinery.
KW  - maintenance of genomic integrity
KW  - ageing
KW  - sex
KW  - DNA damage
KW  - base excision repair (incision activity)
KW  - DNA damage response
KW  - poly(ADP-ribosyl)ation
KW  - liver
Y1  - 2020
U6  - https://doi.org/10.3390/ijms21186600
SN  - 1422-0067
VL  - 21
IS  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - JOUR
A1  - Ruszkiewicz, Joanna
A1  - de Macedo, Gabriel Teixeira
A1  - Miranda-Vizuete, Antonio
A1  - Teixeira da Rocha, Joao B.
A1  - Bowman, Aaron B.
A1  - Bornhorst, Julia
A1  - Schwerdtle, Tanja
A1  - Aschner, Michael
T1  - The cytoplasmic thioredoxin system in Caenorhabditis elegans affords protection from methylmercury in an age-specific manner
JF  - Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system
N2  - Methylmercury (MeHg) is an environmental pollutant linked to many neurological defects, especially in developing individuals. The thioredoxin (TRX) system is a key redox regulator affected by MeHg toxicity, however the mechanisms and consequences of MeHg-induced dysfunction are not completely understood. This study evaluated the role of the TRX system in C. elegans susceptibility to MeHg during development. Worms lacking or overexpressing proteins from the TRX family were exposed to MeHg for 1 h at different developmental stage: L1, L4 and adult. Worms without cytoplasmic thioredoxin system exhibited age-specific susceptibility to MeHg when compared to wild-type (wt). This susceptibility corresponded partially to decreased total glutathione (GSH) levels and enhanced degeneration of dopaminergic neurons. In contrast, the overexpression of the cytoplasmic system TRX-1/TRXR-1 did not provide substantial protection against MeHg. Moreover, transgenic worms exhibited decreased protein expression for cytoplasmic thioredoxin reductase (TRXR-1). Both mitochondrial thioredoxin system TRX-2/TRXR-2, as well as other thioredoxin-like proteins: TRX-3, TRX-4, TRX-5 did not show significant role in C. elegans resistance to MeHg. Based on the current findings, the cytoplasmic thioredoxin system TRX-1/TRXR-1 emerges as an important age-sensitive protectant against MeHg toxicity in C. elegans.
KW  - Methylmercury
KW  - Age
KW  - Development
KW  - C. elegans
KW  - Thioredoxin
KW  - Thioredoxin reductase
Y1  - 2018
U6  - https://doi.org/10.1016/j.neuro.2018.08.007
SN  - 0161-813X
SN  - 1872-9711
VL  - 68
SP  - 189
EP  - 202
PB  - Elsevier
CY  - Amsterdam
ER  -