TY  - JOUR
A1  - Bzymek, Robert
A1  - Horsthemke, Markus
A1  - Isfort, Katrin
A1  - Mohr, Simon
A1  - Tjaden, Kerstin
A1  - Mueller-Tidow, Carsten
A1  - Thomann, Marlies
A1  - Schwerdtle, Tanja
A1  - Baehler, Martin
A1  - Schwab, Albrecht
A1  - Hanley, Peter J.
T1  - Real-time two- and three-dimensional imaging of monocyte motility and navigation on planar surfaces and in collagen matrices: roles of Rho
JF  - Scientific reports
N2  - We recently found that macrophages from RhoA/RhoB double knockout mice had increased motility of the cell body, but severely impaired retraction of the tail and membrane extensions, whereas RhoA-or RhoB-deficient cells exhibited mild phenotypes. Here we extended this work and investigated the roles of Rho signaling in primary human blood monocytes migrating in chemotactic gradients and in various settings. Monocyte velocity, but not chemotactic navigation, was modestly dependent on Rho-ROCK-myosin II signaling on a 2D substrate or in a loose collagen type I matrix. Viewed by time-lapse epi-fluorescence microscopy, monocytes appeared to flutter rather than crawl, such that the 3D surface topology of individual cells was difficult to predict. Spinning disk confocal microscopy and 3D reconstruction revealed that cells move on planar surfaces and in a loose collagen matrix using prominent, curved planar protrusions, which are rapidly remodeled and reoriented, as well as resorbed. In a dense collagen type I matrix, there is insufficient space for this mode and cells adopt a highly Rho-dependent, lobular mode of motility. Thus, in addition to its role in tail retraction on 2D surfaces, Rho is critical for movement in confined spaces, but is largely redundant for motility and chemotaxis in loose matrices.
Y1  - 2016
U6  - https://doi.org/10.1038/srep25016
SN  - 2045-2322
VL  - 6
PB  - Nature Publ. Group
CY  - London
ER  - 
TY  - JOUR
A1  - Ebert, Franziska
A1  - Thomann, Marlies
A1  - Witt, Barbara
A1  - Müller, Sandra Marie
A1  - Meyer, Sören
A1  - Weber, Till
A1  - Christmann, Markus
A1  - Schwerdtle, Tanja
T1  - Evaluating long-term cellular effects of the arsenic species thio-DMA(V): qPCR-based gene expression as screening tool
JF  - Journal of trace elements in medicine and biology
N2  - Thio-dimethylarsinic acid (thio-DMA(V)) is a human urinary metabolite of the class 1 human carcinogen inorganic arsenic as well as of arsenosugars. Thio-DMA(V) exerts strong cellular toxicity, whereas its toxic modes of action are not fully understood. For the first time, this study characterises the impact of a long-term (21 days) in vitro incubation of thio-DMA(V) on the expression of selected genes related to cell death, stress response, epigenetics and DNA repair. The observed upregulation of DNMT1 might be a cellular compensation to counterregulate the in a very recent study observed massive global DNA hypomethylation after chronic thio-DMAv incubation. Moreover, our data suggest that chronic exposure towards subcytotoxic, pico- to nanomolar concentrations of thio-DMA(V) causes a stress response in human urothelial cells. The upregulation of genes encoding for proteins of DNA repair (Apex1,Lig1, XRCC1,DDB2, XPG, ATR) as well as damage response (GADD45A, GADD45G, Trp53) indicate a potential genotoxic risk emanating from thio-DMA(V) after long-term incubation. (C) 2016 Elsevier GmbH. All rights reserved.
KW  - Thio-dimethylarsinic acid
KW  - Long-term cellular toxicity
KW  - qPCR-based gene expression screening
KW  - GADD45A and GADD45G
KW  - DNMT1
KW  - Cellular damage response
Y1  - 2016
U6  - https://doi.org/10.1016/j.jtemb.2016.06.004
SN  - 0946-672X
VL  - 37
SP  - 78
EP  - 84
PB  - Yokohama Publishers
CY  - Jena
ER  -