@article{PatheNeuschaeferRubeNeuschaeferRubeGenzetal.2015,
  author    = {Pathe-Neuschaefer-Rube, Andrea and Neuschaefer-Rube, Frank and Genz, Lara and P{\"u}schel, Gerhard Paul},
  title     = {Botulinum Neurotoxin Dose-Dependently Inhibits Release of Neurosecretory Vesicle-Targeted Luciferase from Neuronal Cells},
  series = {Alternatives to animal experimentation : ALTEX ; a journal for new paths in biomedical science},
  volume    = {32},
  journal   = {Alternatives to animal experimentation : ALTEX ; a journal for new paths in biomedical science},
  number    = {4},
  publisher = {Springer},
  address   = {Heidelberg},
  issn      = {1868-596X},
  pages     = {297 -- 306},
  year      = {2015},
  abstract  = {Botulinum toxin is a bacterial toxin that inhibits neurotransmitter release from neurons and thereby causes a flaccid paralysis. It is used as drug to treat a number of serious ailments and, more frequently, for aesthetic medical interventions. Botulinum toxin for pharmacological applications is isolated from bacterial cultures. Due to partial denaturation of the protein, the specific activity of these preparations shows large variations. Because of its extreme potential toxicity, pharmacological preparations must be carefully tested for their activity. For the current gold standard, the mouse lethality assay, several hundred thousand mice are killed per year. Alternative methods have been developed that suffer from one or more of the following deficits: In vitro enzyme assays test only the activity of the catalytic subunit of the toxin. Enzymatic and cell based immunological assays are specific for just one of the different serotypes. The current study takes a completely different approach that overcomes these limitations: Neuronal cell lines were stably transfected with plasmids coding for luciferases of different species, which were N-terminally tagged with leader sequences that redirect the luciferase into neuro-secretory vesicles. From these vesicles, luciferases were released upon depolarization of the cells. The depolarization-dependent release was efficiently inhibited by botulinum toxin in a concentration range (1 to 100 pM) that is used in pharmacological preparations. The new assay might thus be an alternative to the mouse lethality assay and the immunological assays already in use.},
  language  = {en}
}
@article{NeuschaeferRubeSchraplauScheweetal.2015,
  author    = {Neuschaefer-Rube, Frank and Schraplau, Anne and Schewe, Bettina and Lieske, Stefanie and Kruetzfeldt, Julia-Mignon and Ringel, Sebastian and Henkela, Janin and Birkenfeld, Andreas L. and P{\"u}schel, Gerhard Paul},
  title     = {Arylhydrocarbon receptor-dependent mIndy (SIc13a5) induction as possible contributor to benzo[a]pyrene-induced lipid accumulation in hepatocytes},
  series = {Toxicology},
  volume    = {337},
  journal   = {Toxicology},
  publisher = {Elsevier},
  address   = {Clare},
  issn      = {0300-483X},
  doi       = {10.1016/j.tox.2015.08.007},
  pages     = {1 -- 9},
  year      = {2015},
  abstract  = {Non-alcoholic fatty liver disease is a growing problem in industrialized and developing countries. Hepatic lipid accumulation is the result of an imbalance between fatty acid uptake, fatty acid de novo synthesis, beta-oxidation and secretion of triglyceride-rich lipoproteins from the hepatocyte. A central regulator of hepatic lipid metabolism is cytosolic citrate that can either be derived from the mitochondrium or be taken up from the blood via the plasma membrane sodium citrate transporter NaCT, the product of the mammalian INDY gene (SLC13A5). mINDY ablation protects against diet-induced steatosis whereas mINDY expression is increased in patients with hepatic steatosis. Diet-induced hepatic steatosis is also enhanced by activation of the arylhyrocarbon receptor (AhR) both in humans and animal models. Therefore, the hypothesis was tested whether the mINDY gene might be a target of the AhR. In accordance with such a hypothesis, the AhR activator benzo[a]pyrene induced the mINDY expression in primary cultures of rat hepatocytes in an AhR-dependent manner. This induction resulted in an increased citrate uptake and citrate incorporation into lipids which probably was further enhanced by the benzo[a]pyrene-dependent induction of key enzymes of fatty acid synthesis. A potential AhR binding site was identified in the mINDY promoter that appears to be conserved in the human promoter. Elimination or mutation of this site largely abolished the activation of the mINDY promoter by benzo[a]pyrene. This study thus identified the mINDY as an AhR target gene. AhR-dependent induction of the mINDY gene might contribute to the development of hepatic steatosis. (C) 2015 Elsevier Ireland Ltd. All rights reserved.},
  language  = {en}
}