@article{HoffmannSchmidtKeimetal.2011,
  author    = {Hoffmann, Linda S and Schmidt, Peter M and Keim, Yvonne and Hoffmann, Carsten and Schmidt, Harald H H W and Stasch, Johannes-Peter},
  title     = {Fluorescence Dequenching Makes Haem-Free Soluble Guanylate Cyclase Detectable in Living Cells},
  series = {PLOS ONE},
  volume    = {6},
  journal   = {PLOS ONE},
  number    = {8},
  doi       = {10.1371/journal.pone.0023596},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-139631},
  pages     = {e23596},
  year      = {2011},
  abstract  = {In cardiovascular disease, the protective NO/sGC/cGMP signalling-pathway is impaired due to a decreased pool of NO-sensitive haem-containing sGC accompanied by a reciprocal increase in NO-insensitive haem-free sGC. However, no direct method to detect cellular haem-free sGC other than its activation by the new therapeutic class of haem mimetics, such as BAY 58-2667, is available. Here we show that fluorescence dequenching, based on the interaction of the optical active prosthetic haem group and the attached biarsenical fluorophor FlAsH can be used to detect changes in cellular sGC haem status. The partly overlap of the emission spectrum of haem and FlAsH allows energy transfer from the fluorophore to the haem which reduces the intensity of FlAsH fluorescence. Loss of the prosthetic group, e. g. by oxidative stress or by replacement with the haem mimetic BAY 58-2667, prevented the energy transfer resulting in increased fluorescence. Haem loss was corroborated by an observed decrease in NO-induced sGC activity, reduced sGC protein levels, and an increased effect of BAY 58-2667. The use of a haem-free sGC mutant and a biarsenical dye that was not quenched by haem as controls further validated that the increase in fluorescence was due to the loss of the prosthetic haem group. The present approach is based on the cellular expression of an engineered sGC variant limiting is applicability to recombinant expression systems. Nevertheless, it allows to monitor sGC's redox regulation in living cells and future enhancements might be able to extend this approach to in vivo conditions.},
  language  = {en}
}
@article{ZanuccoGoetzPotapenkoetal.2011,
  author    = {Zanucco, Emanuele and G{\"o}tz, Rudolf and Potapenko, Tamara and Carraretto, Irene and Ceteci, Semra and Ceteci, Fatih and Seeger, Werner and Savai, Rajkumar and Rapp, Ulf R.},
  title     = {Expression of B-RAF V600E in Type II Pneumocytes Causes Abnormalities in Alveolar Formation, Airspace Enlargement and Tumor Formation in Mice},
  series = {PLOS ONE},
  volume    = {6},
  journal   = {PLOS ONE},
  number    = {12},
  doi       = {10.1371/journal.pone.0029093},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-137061},
  pages     = {e29093},
  year      = {2011},
  abstract  = {Growth factor induced signaling cascades are key regulatory elements in tissue development, maintenance and regeneration. Perturbations of these cascades have severe consequences, leading to developmental disorders and neoplastic diseases. As a major function in signal transduction, activating mutations in RAF family kinases are the cause of human tumorigenesis, where B-RAF V600E has been identified as the prevalent mutant. In order to address the oncogenic function of B-RAF V600E, we have generated transgenic mice expressing the activated oncogene specifically in lung alveolar epithelial type II cells. Constitutive expression of B-RAF V600E caused abnormalities in alveolar epithelium formation that led to airspace enlargements. These lung lesions showed signs of tissue remodeling and were often associated with chronic inflammation and low incidence of lung tumors. The inflammatory cell infiltration did not precede the formation of the lung lesions but was rather accompanied with late tumor development. These data support a model where the continuous regenerative process initiated by oncogenic B-RAF-driven alveolar disruption provides a tumor-promoting environment associated with chronic inflammation.},
  language  = {en}
}