@phdthesis{Kirchner2010,
  author    = {Kirchner, Henriette},
  title     = {The ghrelin system links dietary lipids with the endocrine control of energy homeostasis},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-52393},
  school      = {Universit{\"a}t Potsdam},
  year      = {2010},
  abstract  = {Ghrelin is a unique hunger-inducing stomach-borne hormone. It activates orexigenic circuits in the central nervous system (CNS) when acylated with a fatty acid residue by the Ghrelin O-acyltransferase (GOAT). Soon after the discovery of ghrelin a theoretical model emerged which suggests that the gastric peptide ghrelin is the first "meal initiation molecule},
  language  = {en}
}
@phdthesis{Moerbt2010,
  author    = {M{\"o}rbt, Nora},
  title     = {Differential proteome analysis of human lung epithelial cells following exposure to aromatic volatile organic compounds},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus-49257},
  school      = {Universit{\"a}t Potsdam},
  year      = {2010},
  abstract  = {The widespread usage of products containing volatile organic compounds (VOC) has lead to a general human exposure to these chemicals in work places or homes being suspected to contribute to the growing incidence of environmental diseases. Since the causal molecular mechanisms for the development of these disorders are not completely understood, the overall objective of this thesis was to investigate VOC-mediated molecular effects on human lung cells in vitro at VOC concentrations comparable to exposure scenarios below current occupational limits. Although differential expression of single proteins in response to VOCs has been reported, effects on complex protein networks (proteome) have not been investigated. However, this information is indispensable when trying to ascertain a mechanism for VOC action on the cellular level and establishing preventive strategies. For this study, the alveolar epithelial cell line A549 has been used. This cell line, cultured in a two-phase (air/liquid) model allows the most direct exposure and had been successfully applied for the analysis of inflammatory effects in response to VOCs. Mass spectrometric identification of 266 protein spots provided the first proteomic map of A549 cell line to this extent that may foster future work with this frequently used cellular model. The distribution of three typical air contaminants, monochlorobenzene (CB), styrene and 1,2 dichlorobenzene (1,2-DCB), between gas and liquid phase of the exposure model has been analyzed by gas chromatography. The obtained VOC partitioning was in agreement with available literature data. Subsequently the adapted in vitro system has been successfully employed to characterize the effects of the aromatic compound styrene on the proteome of A549 cells (Chapter 4). Initially, the cell toxicity has been assessed in order to ensure that most of the concentrations used in the following proteomic approach were not cytotoxic. Significant changes in abundance and phosphorylation in the total soluble protein fraction of A549 cells have been detected following styrene exposure. All proteins have been identified using mass spectrometry and the main cellular functions have been assigned. Validation experiments on protein and transcript level confirmed the results of the 2-DE experiments. From the results, two main cellular pathways have been identified that were induced by styrene: the cellular oxidative stress response combined with moderate pro-apoptotic signaling. Measurement of cellular reactive oxygen species (ROS) as well as the styrene-mediated induction of oxidative stress marker proteins confirmed the hypothesis of oxidative stress as the main molecular response mechanism. Finally, adducts of cellular proteins with the reactive styrene metabolite styrene 7,8 oxide (SO) have been identified. Especially the SO-adducts observed at both the reactive centers of thioredoxin reductase 1, which is a key element in the control of the cellular redox state, may be involved in styrene-induced ROS formation and apoptosis. A similar proteomic approach has been carried out with the halobenzenes CB and 1,2-DCB (Chapter 5). In accordance with previous findings, cell toxicity assessment showed enhanced toxicity compared to the one caused by styrene. Significant changes in abundance and phosphorylation of total soluble proteins of A549 cells have been detected following exposure to subtoxic concentrations of CB and 1,2-DCB. All proteins have been identified using mass spectrometry and the main cellular functions have been assigned. As for the styrene experiment, the results indicated two main pathways to be affected in the presence of chlorinated benzenes, cell death signaling and oxidative stress response. The strong induction of pro-apoptotic signaling has been confirmed for both treatments by detection of the cleavage of caspase 3. Likewise, the induction of redox-sensitive protein species could be correlated to an increased cellular level of ROS observed following CB treatment. Finally, common mechanisms in the cellular response to aromatic VOCs have been investigated (Chapter 6). A similar number (4.6-6.9\%) of all quantified protein spots showed differential expression (p<0.05) following cell exposure to styrene, CB or 1,2-DCB. However, not more than three protein spots showed significant regulation in the same direction for all three volatile compounds: voltage-dependent anion-selective channel protein 2, peroxiredoxin 1 and elongation factor 2. However, all of these proteins are important molecular targets in stress- and cell death-related signaling pathways.},
  language  = {en}
}
@article{GereckeSchneiderScholtka2010,
  author    = {Gerecke, Christian and Schneider, Mandy and Scholtka, Bettina},
  title     = {Vimentin promoter methylation analysis is a suitable complement of a gene mutation marker panel for the detection of preneoplastic and neoplastic colonic lesions},
  issn      = {0378-584X},
  doi       = {10.1159/000290860},
  year      = {2010},
  abstract  = {Abstracts: Strukturen veraendern - Heilung verbessern. 29. Deutscher Krebskongress. Berlin 24.-27. Februar 201},
  language  = {en}
}
@article{ScholtkaBrossuleit2010,
  author    = {Scholtka, Bettina and Brossuleit, K.},
  title     = {Procedure for the highly sensitive enrichment and detection of the K-RAS codon 12 mutation in faeces from patients with colorectal cancer precursors},
  issn      = {0378-584X},
  year      = {2010},
  language  = {en}
}
@phdthesis{Wohlgemuth2010,
  author    = {Wohlgemuth, Steffen},
  title     = {Microbial and host factors associated with chronic intestinal inflammation of the Interleukin-10 deficient mouse},
  address   = {Potsdam},
  pages     = {IX, 125 Bl. : Ill., graph. Darst.},
  year      = {2010},
  language  = {en}
}
@article{SharkovskaKalkLawrenzetal.2010,
  author    = {Sharkovska, Yuliya and Kalk, Philipp and Lawrenz, Bettina and Godes, Michael and Hoffmann, Linda Sarah and Wellkisch, Kathrin and Geschka, Sandra and Relle, Katharina and Hocher, Berthold and Stasch, Johannes-Peter},
  title     = {Nitric oxide-independent stimulation of soluble guanylate cyclase reduces organ damage in experimental low- renin and high-renin models},
  issn      = {0263-6352},
  doi       = {10.1097/Hjh.0b013e32833b558c},
  year      = {2010},
  abstract  = {Objectives The nitric oxide-soluble guanylate cyclase (sGC)-cGMP signal transduction pathway is impaired in different cardiovascular diseases, including pulmonary hypertension, heart failure and arterial hypertension. Riociguat is a novel stimulator of soluble guanylate cyclase (sGC). However, little is known about the effects of sGC stimulators in experimental models of hypertension. We thus investigated the cardio-renal protective effects of riociguat in low- renin and high-renin rat models of hypertension. Methods The vasorelaxant effect of riociguat was tested in vitro on isolated saphenous artery rings of normal and nitrate tolerant rabbits. The cardiovascular in-vivo effects of sGC stimulation were evaluated in hypertensive renin-transgenic rats treated with the nitric oxide-synthase inhibitor N- nitro-L-arginine methyl ester (L-NAME) (high-renin model) and in rats with 5/6 nephrectomy (low-renin model). Results In both animal models, riociguat treatment improved survival and normalized blood pressure. Moreover, in the L-NAME study part, riociguat reduced cardiac target organ damage as indicated by lower plasma ANP, lower relative left ventricular weight and lower cardiac interstitial fibrosis, and reduced renal target organ damage as indicated by lower plasma creatinine and urea, less glomerulosclerosis and less renal interstitial fibrosis. In the 5/6 nephrectomy study part, riociguat reduced cardiac target organ damage as indicated by lower plasma ANP, lower relative left ventricular weight, lower myocyte diameter and lower arterial media/lumen ratio, and reduced renal target organ damage as indicated by improved creatinine clearance and less renal interstitial fibrosis. Conclusion We demonstrate for the first time that the novel sGC stimulator riociguat shows in two independent models of hypertension a potent protection against cardiac and renal target organ damage. J Hypertens 28: 1666-1675 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams \& Wilkins.},
  language  = {en}
}
@phdthesis{Gerber2010,
  author    = {Gerber, Chimgee Baasanjav},
  title     = {Detection and identification of genotoxicant from brassica plants},
  address   = {Potsdam},
  pages     = {191 S.},
  year      = {2010},
  language  = {en}
}
@article{FischerKempeLeibrocketal.2010,
  author    = {Fischer, Stephanie S. and Kempe, Daniela S. and Leibrock, Christina B. and Rexhepaj, Rexhep and Siraskar, Balasaheb and Boini, Krishna M. and Ackermann, Teresa F. and Foeller, Michael and Hocher, Berthold and Rosenblatt, Kevin P. and Kuro-o, Makoto and Lang, Florian},
  title     = {Hyperaldosteronism in Klotho-deficient mice},
  issn      = {1931-857X},
  doi       = {10.1152/ajprenal.00233.2010},
  year      = {2010},
  abstract  = {Klotho is a membrane protein participating in the inhibitory effect of FGF23 on the formation of 1,25- dihydroxyvitamin-D-3 [1,25(OH)(2)D-3]. It participates in the regulation of renal tubular phosphate reabsorption and stimulates renal tubular Ca2+ reabsorption. Klotho hypomorphic mice (klotho(hm)) suffer from severe growth deficit, rapid aging, and early death, events largely reversed by a vitamin D-deficient diet. The present study explored the role of Klotho deficiency in mineral and electrolyte metabolism. To this end, klothohm mice and wild-type mice (klotho(+/+)) were subjected to a normal (D+) or vitamin D-deficient (D-) diet or to a vitamin D-deficient diet for 4 wk and then to a normal diet (D-/+). At the age of 8 wk, body weight was significantly lower in klotho(hm)D(+) mice than in klotho(+/ +)D(+) mice, klotho(hm)D(-) mice, and klotho(hm)D(-/+) mice. Plasma concentrations of 1,25(OH)(2)D-3, adrenocorticotropic hormone (ACTH), antidiuretic hormone (ADH), and aldosterone were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. Plasma volume was significantly smaller in klotho(hm)D(-/+) mice, and plasma urea, Ca2+, phosphate and Na+, but not K+ concentrations were significantly higher in klotho(hm)D(+) mice than in klotho(+/+)D(+) mice. The differences were partially abrogated by a vitamin D-deficient diet. Moreover, the hyperaldosteronism was partially reversed by Ca2+-deficient diet. Ussing chamber experiments revealed a marked increase in amiloride-sensitive current across the colonic epithelium, pointing to enhanced epithelial sodium channel (ENaC) activity. A salt-deficient diet tended to decrease and a salt-rich diet significantly increased the life span of klotho(hm)D(+) mice. In conclusion, the present observation disclose that the excessive formation of 1,25(OH)(2)D-3 in Klotho-deficient mice results in extracellular volume depletion, which significantly contributes to the shortening of life span.},
  language  = {en}
}
@article{FoellerMahmudQadrietal.2010,
  author    = {Foeller, Michael and Mahmud, Hasan and Qadri, Syed M. and Gu, Shuchen and Braun, Manuel and Bobbala, Diwakar and Hocher, Berthold and Lang, Florian},
  title     = {Endothelin B receptor stimulation inhibits suicidal erythrocyte death},
  issn      = {0892-6638},
  doi       = {10.1096/Fj.10-159483},
  year      = {2010},
  abstract  = {Endothelins (ETs), potent endothelium-derived mediators, stimulate formation of nitric oxide, which, in turn, protects against suicidal erythrocyte death or eryptosis, characterized by phosphatidylserine exposure at the erythrocyte surface and triggered by increase in cytosolic Ca2+ ([Ca2+](i)). The present study explored whether the ET1- receptor ETB influences suicidal erythrocyte death. To this end, [Ca2+](i) (Fluo3-fluorescence) and phosphatidylserine exposure (annexin V-binding) were determined utilizing FACS analysis. Energy depletion increased [Ca2+]i and phosphatidylserine-exposure, effects significantly blunted by ET1 (IC50 approximate to 100 nM) and the ETB receptor- agonist sarafotoxin 6c (IC50 approximate to 10 nM) but not by ET2 and ET3. ET1 and sarafotoxin significantly delayed the kinetics of suicidal erythrocyte death following energy depletion. ETB stimulation did not blunt the effect of Ca2+- ionophore ionomycin (1 mu M) on phosphatidylserine exposure. The in vivo significance was tested using rescued ETB- knockout (etb(-/-)) and wild-type (etb(+/+)) mice. The number of phosphatidylserine-exposing erythrocytes, of reticulocytes and spleen size were significantly larger in etb(-/-) mice than in etb(+/+)-mice. The etb(-/-) erythrocytes were more susceptible to the eryptotic effect of oxidative stress and more rapidly cleared from circulating blood than etb(+/+) erythrocytes. Finally, the spleens from etb(-/-) mice were enlarged and contained markedly more phosphatidylserine- exposing erythrocytes than spleens from etb(+/+) mice. The observations disclose a novel function of ET1, i. e., protection from suicidal erythrocyte death.},
  language  = {en}
}
@article{FritzscheSchuchardtSchmidtetal.2010,
  author    = {Fritzsche, Britta and Schuchardt, Jan-Philipp and Schmidt, Anja and Nau, Heinz and Schweigert, Florian J. and Ruehl, Ralph},
  title     = {CYP26A1-specific antagonist influence on embryonic implantation, gene expression and endogenous retinoid concentration in rats},
  issn      = {0890-6238},
  doi       = {10.1016/j.reprotox.2010.05.005},
  year      = {2010},
  abstract  = {Retinoids are essential in vertebrate reproduction and embryonic development. All-trans-retinoic acid (ATRA) is tightly regulated during these processes. CYP26A1 is mainly responsible for its degradation. To study the role of CYP26A1 during implantation, we applied R115866, a CYP26A1-specific antagonist, to rats during early gestation days (GD). On GD 6.5 and 12 samples were collected and the number of embryos was evaluated. ATRA concentration increased in uterus and serum, mRNA expression of CYP26A1 and CRABP2 increased in the liver, but not in the uterus. Uterine COX1 and 17 beta HSD mRNA expression was decreased. The number of embryos on GD 12 was not altered in this setting. It can be concluded that uterine expression of the analyzed retinoid-response genes during early gestation is not altered by this R115866 treatment and instead indirectly via ATRA. From our experiment we cannot confirm that ATRA obtains a major influencing role in the regulation of embryonic implantation.},
  language  = {en}
}