@article{FrancoObregonCambriaGreutertetal.2018,
  author    = {Franco-Obregon, Alfredo and Cambria, Elena and Greutert, Helen and Wernas, Timon and Hitzl, Wolfgang and Egli, Marcel and Sekiguchi, Miho and Boos, Norbert and Hausmann, Oliver and Ferguson, Stephen J. and Kobayashi, Hiroshi and W{\"u}rtz-Kozak, Karin},
  title     = {TRPC6 in simulated microgravity of intervertebral disc cells},
  series = {European Spine Journal},
  volume    = {27},
  journal   = {European Spine Journal},
  number    = {10},
  publisher = {Springer},
  address   = {New York},
  issn      = {0940-6719},
  doi       = {10.1007/s00586-018-5688-8},
  pages     = {2621 -- 2630},
  year      = {2018},
  abstract  = {Purpose Prolonged bed rest and microgravity in space cause intervertebral disc (IVD) degeneration. However, the underlying molecular mechanisms are not completely understood. Transient receptor potential canonical (TRPC) channels are implicated in mechanosensing of several tissues, but are poorly explored in IVDs. Methods Primary human IVD cells from surgical biopsies composed of both annulus fibrosus and nucleus pulposus (passage 1-2) were exposed to simulated microgravity and to the TRPC channel inhibitor SKF-96365 (SKF) for up to 5days. Proliferative capacity, cell cycle distribution, senescence and TRPC channel expression were analyzed. Results Both simulated microgravity and TRPC channel antagonism reduced the proliferative capacity of IVD cells and induced senescence. While significant changes in cell cycle distributions (reduction in G1 and accumulation in G2/M) were observed upon SKF treatment, the effect was small upon 3days of simulated microgravity. Finally, downregulation of TRPC6 was shown under simulated microgravity. Conclusions Simulated microgravity and TRPC channel inhibition both led to reduced proliferation and increased senescence. Furthermore, simulated microgravity reduced TRPC6 expression. IVD cell senescence and mechanotransduction may hence potentially be regulated by TRPC6 expression. This study thus reveals promising targets for future studies.},
  language  = {en}
}
@article{MuellerFinkeEbertetal.2018,
  author    = {M{\"u}ller, S. M. and Finke, Hannah and Ebert, Franziska and Kopp, Johannes Florian and Schumacher, Fabian and Kleuser, Burkhard and Francesconi, Kevin A. and Raber, G. and Schwerdtle, Tanja},
  title     = {Arsenic-containing hydrocarbons},
  series = {Archives of toxicology : official journal of EUROTOX},
  volume    = {92},
  journal   = {Archives of toxicology : official journal of EUROTOX},
  number    = {5},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {0340-5761},
  doi       = {10.1007/s00204-018-2194-z},
  pages     = {1751 -- 1765},
  year      = {2018},
  abstract  = {Arsenic-containing hydrocarbons (AsHCs), a subgroup of arsenolipids found in fish and algae, elicit substantial toxic effects in various human cell lines and have a considerable impact on cellular energy levels. The underlying mode of action, however, is still unknown. The present study analyzes the effects of two AsHCs (AsHC 332 and AsHC 360) on the expression of 44 genes covering DNA repair, stress response, cell death, autophagy, and epigenetics via RT-qPCR in human liver (HepG2) cells. Both AsHCs affected the gene expression, but to different extents. After treatment with AsHC 360, flap structure-specific endonuclease 1 (FEN1) as well as xeroderma pigmentosum group A complementing protein (XPA) and (cytosine-5)-methyltransferase 3A (DNMT3A) showed time- and concentration-dependent alterations in gene expression, thereby indicating an impact on genomic stability. In the subsequent analysis of epigenetic markers, within 72 h, neither AsHC 332 nor AsHC 360 showed an impact on the global DNA methylation level, whereas incubation with AsHC 360 increased the global DNA hydroxymethylation level. Analysis of cell extracts and cell media by HPLC-mass spectrometry revealed that both AsHCs were considerably biotransformed. The identified metabolites include not only the respective thioxo-analogs of the two AsHCs, but also several arsenic-containing fatty acids and fatty alcohols, contributing to our knowledge of biotransformation mechanisms of arsenolipids.},
  language  = {en}
}