@article{ErrardUlrichsKuehneetal.2015, author = {Errard, Audrey and Ulrichs, Christian and Kuehne, Stefan and Mewis, Inga and Drungowski, Mario and Schreiner, Monika and Baldermann, Susanne}, title = {Single- versus multiple-pest infestation affects differently the Biochemistry of Tomato (Solanum lycopersicum 'Ailsa Craig')}, series = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, volume = {63}, journal = {Journal of agricultural and food chemistry : a publication of the American Chemical Society}, number = {46}, publisher = {American Chemical Society}, address = {Washington}, issn = {0021-8561}, doi = {10.1021/acs.jafc.5b03884}, pages = {10103 -- 10111}, year = {2015}, abstract = {Tomato is susceptible to pest infestations by both spider mites and aphids. The effects of each individual pest on plants are known, whereas multiple-pest infestations have received little interest. We studied the effects of single-versus multiple-pest infestation by Tetranychus urticae and Myzus persicae on tomato biochemistry (Solanum lycopersicum) by combining a metabolomic approach and analyses of carotenoids using UHPLC-ToF-MS and volatiles using GC-MS. Plants responded differently to aphids and mites after 3 weeks of infestation, and a multiple infestation induced a specific metabolite composition in plants. In addition, we showed that volatiles emissions differed between the adaxial and abaxial leaf epidermes and identified compounds emitted particularly in response to a multiple infestation (cyclohexadecane, dodecane, aromadendrene, and beta-elemene). Finally, the carotenoid concentrations in leaves and stems were more affected by multiple than single infestations. Our study highlights and discusses the interplay of biotic stressors within the terpenoid metabolism.}, language = {en} } @article{ErrardBaldermannKuehneetal.2015, author = {Errard, Audrey and Baldermann, Susanne and K{\"u}hne, Stefan and Mewis, Inga and Peterkin, John and Ulrichs, Christian}, title = {Interspecific Interactions Affect Pests Differently}, series = {Gesunde Pflanzen : Pflanzenschutz, Verbraucherschutz, Umweltschutz}, volume = {67}, journal = {Gesunde Pflanzen : Pflanzenschutz, Verbraucherschutz, Umweltschutz}, number = {4}, publisher = {Springer}, address = {New York}, issn = {0367-4223}, doi = {10.1007/s10343-015-0349-x}, pages = {183 -- 190}, year = {2015}, abstract = {Spider mites, Tetranychus urticae Koch (Acari: Tetranychidae) and aphids, Myzus persicae (Sulzer) (Pterygota: Aphididae) share many host-plants, similar abiotic conditions and are world-wide distributed therefore, they often occur simultaneously in crops. However, the effects of interspecific interactions on the biology of these pests were poorly investigated. To test if they perform differently under intra- versus inter-specific interactions, host-plant acceptance, fecundity, survival, the total number of individuals and the rate of increase in the number of individuals were studied doing non-choice bioassays under laboratory conditions with leaf discs of tomato (Solanum lycopersicum L. 'Ailsa Craig'), pak choi (Brassica rapa L. var. chinensis 'Black Behi') and bean (Phaseolus vulgaris L. 'Saxa'). Alone, the pests differently accepted the host-plants. The acceptance of pak choi by spider mites was lower under interspecific interactions and higher on tomato for aphids. In general, spider mites' performance decreased when aphids were present; the fecundity, the number of individuals and the rate of increase being significantly lower on pak choi and bean. In contrast, aphids produced more offspring in the presence of spider mites, leading to a higher rate of increase in aphids individuals on tomato and pak choi. Thus, pest' responses to interspecific interactions is species-specific.}, language = {en} } @article{LaurenzanaCencettiSerratietal.2015, author = {Laurenzana, Anna and Cencetti, Francesca and Serrati, Simona and Bruno, Gennaro and Japtok, Lukasz and Bianchini, Francesca and Torre, Eugenio and Fibbi, Gabriella and Del Rosso, Mario and Bruni, Paola and Donati, Chiara}, title = {Endothelial sphingosine kinase/SPNS2 axis is critical for vessel-like formation by human mesoangioblasts}, series = {Journal of molecular medicine}, volume = {93}, journal = {Journal of molecular medicine}, number = {10}, publisher = {Springer}, address = {New York}, issn = {0946-2716}, doi = {10.1007/s00109-015-1292-0}, pages = {1145 -- 1157}, year = {2015}, abstract = {The interaction between endothelial cells and pericytes is crucial for the stabilization of newly formed vessels in angiogenesis. The comprehension of the mechanisms regulating peiicyte recruitment might open therapeutical perspectives on vascular-related pathologies. Sphingosine 1phosphate (SIP) is a bioactive sphingolipid that derives from sphingomyelin catabolism and regulates biological functions in cell survival, proliferation, and differentiation. In this study, we aimed to identify the role of SIP axis in the intercellular communication between human mesenchymal progenitor mesoangioblasts (MAB) and endothelial cells (human microvascular endothelial cells (HMVEC)) in the formation of capillary-like structures. We demonstrated that the SIP biosynthetic pathway brought about by sphingosine kinases (SK) SKI and SK2 as well as spinster homolog 2 (SPNS2) transporter in H-MVEC is crucial for MAB migration measured by Boyden chambers and for the formation and stabilization of capillary-like structures in a 3D Matrigel culture. Moreover, the conditioned medium (CM) harvested from HMVEC, where SKI, 5K2, and SPNS2 were down-regulated, exerted a significantly diminished effect on MAB capillary morphogenesis and migration. Notably, we demonstrated that S I Pi and Si p3 receptors were positively involved in CM-induced capillary-like formation and migration, while S I P2 exerted a negative role on CM-induced migratory action of MAB. Finally, SK inhibition as well as MAB SlPi and S1P3 down-regulation impaired HMVEC-MAB cross-talk significantly reducing in vivo angiogenesis evaluated by Matrigel plug assay. These findings individuate novel targets for the employment of MAB in vascular-related pathologic conditions.}, language = {en} } @article{BrunoCencettiPerticietal.2015, author = {Bruno, Gennaro and Cencetti, Francesca and Pertici, Irene and Japtok, Lukasz and Bernacchioni, Caterina and Donati, Chiara and Bruni, Paola}, title = {CTGF/CCN2 exerts profibrotic action in myoblasts via the up-regulation of sphingosine kinase-1/S1P(3) signaling axis: Implications in the action mechanism of TGF beta}, series = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, volume = {1851}, journal = {Biochimica et biophysica acta : Molecular and cell biology of lipids}, number = {2}, publisher = {Elsevier}, address = {Amsterdam}, issn = {1388-1981}, doi = {10.1016/j.bbalip.2014.11.011}, pages = {194 -- 202}, year = {2015}, abstract = {The matricellular protein connective tissue growth factor (CTGF/CCN2) is recognized as key player in the onset of fibrosis in various tissues, including skeletal muscle. In many circumstances, CTGF has been shown to be induced by transforming growth factor beta (TGF beta) and accounting, at least in part, for its biological action. In this study it was verified that in cultured myoblasts CTGF/CCN2 causes their transdifferentiation into myofibroblasts by up-regulating the expression of fibrosis marker proteins alpha-smooth muscle actin and transgelin. Interestingly, it was also found that the profibrotic effect exerted by CTGF/CCN2 was mediated by the sphingosine kinase (SK)-1/S1P(3) signaling axis specifically induced by the treatment with the profibrotic cue. Following CTGF/CCN2-induced up-regulation, S1P(3) became the SIP receptor subtype expressed at the highest degree, at least at mRNA level, and was thus capable of readdressing the sphingosine 1-phosphate signaling towards fibrosis rather than myogenic differentiation. Another interesting finding is that CTGF/CCN2 silencing prevented the TGF beta-dependent up-regulation of SKI/S1P(3) signaling axis and strongly reduced the profibrotic effect exerted by TGF beta, pointing at a crucial role of endogenous CTGF/CCN2 generated following TGF beta challenge in the transmission of at least part of its profibrotic effect These results provide new insights into the molecular mechanism by which CTGF/CCN2 drives its biological action and strengthen the concept that SK1/S1P(3) axis plays a critical role in the onset of fibrotic cell phenotype. (C) 2014 Elsevier B.V. All rights reserved.}, language = {en} } @article{JaptokSchmitzFayyazetal.2015, author = {Japtok, Lukasz and Schmitz, Elisabeth I. and Fayyaz, Susann and Kr{\"a}mer, Stephanie and Hsu, Leigh J. and Kleuser, Burkhard}, title = {Sphingosine 1-phosphate counteracts insulin signaling in pancreatic beta-cells via the sphingosine 1-phosphate receptor subtype 2}, series = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, volume = {29}, journal = {The FASEB journal : the official journal of the Federation of American Societies for Experimental Biology}, number = {8}, publisher = {Federation of American Societies for Experimental Biology}, address = {Bethesda}, issn = {0892-6638}, doi = {10.1096/fj.14-263194}, pages = {3357 -- 3369}, year = {2015}, abstract = {Glucolipotoxic stress has been identified as a key player in the progression of pancreatic beta-cell dysfunction contributing to insulin resistance and the development of type 2 diabetes mellitus (T2D). It has been suggested that bioactive lipid intermediates, formed under lipotoxic conditions, are involved in these processes. Here, we show that sphingosine 1-phosphate (S1P) levels are not only increased in palmitate-stimulated pancreatic beta-cells but also regulate beta-cell homeostasis in a divergent manner. Although S1P possesses a prosurvival effect in beta-cells, an enhanced level of the sphingolipid antagonizes insulin-mediated cell growth and survival via the sphingosine 1-phosphate receptor subtype 2 (S1P(2)) followed by an inhibition of Akt-signaling. In an attempt to investigate the role of the S1P/S1P(2) axis in vivo, the New Zealand obese (NZO) diabetic mouse model, characterized by beta-cell loss under high-fat diet (HFD) conditions, was used. The occurrence of T2D was accompanied by an increase of plasma S1P levels. To examine whether S1P contributes to the morphologic changes of islets via S1P(2), the receptor antagonist JTE-013 was administered. Most interestingly, JTE-013 rescued beta-cell damage clearly indicating an important role of the S1P(2) in beta-cell homeostasis. Therefore, the present study provides a new therapeutic strategy to diminish beta-cell dysfunction and the development of T2D.}, language = {en} } @article{MichelsJaptokAlisjahbanaetal.2015, author = {Michels, Meta and Japtok, Lukasz and Alisjahbana, Bachti and Wisaksana, Rudi and Sumardi, Uun and Puspita, Mita and Kleuser, Burkhard and de Mast, Quirijn and van der Ven, Andre J. A. M.}, title = {Decreased plasma levels of the endothelial protective sphingosine-1-phosphate are associated with dengue-induced plasma leakage}, series = {Journal of infection}, volume = {71}, journal = {Journal of infection}, number = {4}, publisher = {Elsevier}, address = {London}, issn = {0163-4453}, doi = {10.1016/j.jinf.2015.06.014}, pages = {480 -- 487}, year = {2015}, abstract = {Background: A transient endothelial hyperpermeability is a hallmark of severe dengue infections. Sphingosine-1-phosphate (S1P) maintains vascular integrity and protects against plasma leakage. We related plasma S1P levels to dengue-induced plasma leakage and studied mechanisms that may underlie the decrease in S1P levels in dengue. Methods: We determined circulating levels of S1P in 44 Indonesian adults with acute dengue and related levels to plasma leakage, as determined by daily ultrasonography, and to levels of its chaperone apolipoprotein M, other lipoproteins and platelets. Results: Plasma S1P levels were decreased during dengue and patients with plasma leakage had lower median levels compared to those without (638 vs. 745 nM; p < 0.01). ApoM and other lipoprotein levels were also decreased during dengue, but did not correlate to S1P levels. Platelet counts correlated positively with S1P levels, but S1P levels were not higher in frozen-thawed platelet rich plasma, arguing against platelets as an important cellular source of S1P in dengue. Conclusions: Decreased plasma S1P levels during dengue are associated with plasma leakage. We speculate that decreased levels of ApoM underlies the lower S1P levels. Modulation of S1P levels and its receptors may be a novel therapeutic intervention to prevent plasma leakage in dengue. (C) 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.}, language = {en} } @article{CarpinteiroBeckerJaptoketal.2015, author = {Carpinteiro, Alexander and Becker, Katrin Anne and Japtok, Lukasz and Hessler, Gabriele and Keitsch, Simone and Pozgajova, Miroslava and Schmid, Kurt W. and Adams, Constantin and M{\"u}ller, Stefan and Kleuser, Burkhard and Edwards, Michael J. and Grassme, Heike and Helfrich, Iris and Gulbins, Erich}, title = {Regulation of hematogenous tumor metastasis by acid sphingomyelinase}, series = {EMBO molecular medicine}, volume = {7}, journal = {EMBO molecular medicine}, number = {6}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {1757-4676}, pages = {714 -- 734}, year = {2015}, abstract = {Metastatic dissemination of cancer cells is the ultimate hallmark of malignancy and accounts for approximately 90\% of human cancer deaths. We investigated the role of acid sphingomyelinase (Asm) in the hematogenous metastasis of melanoma cells. Intravenous injection of B16F10 melanoma cells into wild-type mice resulted in multiple lung metastases, while Asm-deficient mice (Smpd1(-/-) mice) were protected from pulmonary tumor spread. Transplanting wild-type platelets into Asm-deficient mice reinstated tumor metastasis. Likewise, Asm-deficient mice were protected from hematogenous MT/ret melanoma metastasis to the spleen in a mouse model of spontaneous tumor metastasis. Human and mouse melanoma cells triggered activation and release of platelet secretory Asm, in turn leading to ceramide formation, clustering, and activation of 51 integrins on melanoma cells finally leading to adhesion of the tumor cells. Clustering of integrins by applying purified Asm or C-16 ceramide to B16F10 melanoma cells before intravenous injection restored trapping of tumor cells in the lung in Asm-deficient mice. This effect was revertable by arginine-glycine-aspartic acid peptides, which are known inhibitors of integrins, and by antibodies neutralizing 1 integrins. These findings indicate that melanoma cells employ platelet-derived Asm for adhesion and metastasis.}, language = {en} } @article{PeresEyngLopesetal.2015, author = {Peres, Tanara V. and Eyng, Helena and Lopes, Samantha C. and Colle, Dirleise and Goncalves, Filipe M. and Venske, Debora K. R. and Lopes, Mark W. and Ben, Juliana and Bornhorst, Julia and Schwerdtle, Tanja and Aschner, Michael A. and Farina, Marcelo and Prediger, Rui D. and Leal, Rodrigo B.}, title = {Developmental exposure to manganese induces lasting motor and cognitive impairment in rats}, series = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, volume = {50}, journal = {Neurotoxicology : the interdisciplinary journal of effects to toxic substances on the nervous system}, publisher = {Elsevier}, address = {Amsterdam}, issn = {0161-813X}, doi = {10.1016/j.neuro.2015.07.005}, pages = {28 -- 37}, year = {2015}, abstract = {Exposure to high manganese (Mn) levels may damage the basal ganglia, leading to a syndrome analogous to Parkinson's disease, with motor and cognitive impairments. The molecular mechanisms underlying Mn neurotoxicity, particularly during development, still deserve further investigation. Herein, we addressed whether early-life Mn exposure affects motor coordination and cognitive function in adulthood and potential underlying mechanisms. Male Wistar rats were exposed intraperitoneally to saline (control) or MnCl2 (5, 10 or 20 mg/kg/day) from post-natal day (PND) 8-12. Behavioral tests were performed on PND 60-65 and biochemical analysis in the striatum and hippocampus were performed on PND14 or PND70. Rats exposed to Mn (10 and 20 mg/kg) performed significantly worse on the rotarod test than controls indicating motor coordination and balance impairments. The object and social recognition tasks were used to evaluate short-term memory. Rats exposed to the highest Mn dose failed to recognize a familiar object when replaced by a novel object as well as to recognize a familiar juvenile rat after a short period of time. However, Mn did not alter olfactory discrimination ability. In addition, Mn-treated rats displayed decreased levels of non-protein thiols (e.g. glutathione) and increased levels of glial fibrillary acidic protein (GFAP) in the striatum. Moreover, Mn significantly increased hippocampal glutathione peroxidase (GPx) activity. These findings demonstrate that acute low-level exposure to Mn during a critical neurodevelopmental period causes cognitive and motor dysfunctions that last into adulthood, that are accompanied by alterations in antioxidant defense system in both the hippocampus and striatum. (C) 2015 Elsevier Inc. All rights reserved.}, language = {en} } @article{CroneAschnerSchwerdtleetal.2015, author = {Crone, Barbara and Aschner, Michael A. and Schwerdtle, Tanja and Karst, Uwe and Bornhorst, Julia}, title = {Elemental bioimaging of Cisplatin in Caenorhabditis elegans by LA-ICP-MS}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {7}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c5mt00096c}, pages = {1189 -- 1195}, year = {2015}, abstract = {cis-Diamminedichloroplatinum(II) (Cisplatin) is one of the most important and frequently used cytostatic drugs for the treatment of various solid tumors. Herein, a laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) method incorporating a fast and simple sample preparation protocol was developed for the elemental mapping of Cisplatin in the model organism Caenorhabditis elegans (C. elegans). The method allows imaging of the spatially-resolved elemental distribution of platinum in the whole organism with respect to the anatomic structure in L4 stage worms at a lateral resolution of 5 mm. In addition, a dose- and time-dependent Cisplatin uptake was corroborated quantitatively by a total reflection X-ray fluorescence spectroscopy (TXRF) method, and the elemental mapping indicated that Cisplatin is located in the intestine and in the head of the worms. Better understanding of the distribution of Cisplatin in this well-established model organism will be instrumental in deciphering Cisplatin toxicity and pharmacokinetics. Since the cytostatic effect of Cisplatin is based on binding the DNA by forming intra- and interstrand crosslinks, the response of poly(ADP-ribose) metabolism enzyme 1 (pme-1) deletion mutants to Cisplatin was also examined. Loss of pme-1, which is the C. elegans ortholog of human poly(ADP-ribose) polymerase 1 (PARP-1) led to disturbed DNA damage response. With respect to survival and brood size, pme-1 deletion mutants were more sensitive to Cisplatin as compared to wildtype worms, while Cisplatin uptake was indistinguishable.}, language = {en} } @article{LohrenBornhorstGallaetal.2015, author = {Lohren, Hanna and Bornhorst, Julia and Galla, Hans-Joachim and Schwerdtle, Tanja}, title = {The blood-cerebrospinal fluid barrier - first evidence for an active transport of organic mercury compounds out of the brain}, series = {Metallomics : integrated biometal science}, volume = {7}, journal = {Metallomics : integrated biometal science}, number = {10}, publisher = {Royal Society of Chemistry}, address = {Cambridge}, issn = {1756-5901}, doi = {10.1039/c5mt00171d}, pages = {1420 -- 1430}, year = {2015}, abstract = {Exposure to organic mercury compounds promotes primarily neurological effects. Although methylmercury is recognized as a potent neurotoxicant, its transfer into the central nervous system (CNS) is not fully evaluated. While methylmercury and thiomersal pass the blood-brain barrier, limited data are available regarding the second brain regulating interface, the blood-cerebrospinal fluid (CSF) barrier. This novel study was designed to investigate the effects of organic as well as inorganic mercury compounds on, and their transfer across, a porcine in vitro model of the blood-CSF barrier for the first time. The barrier system is significantly more sensitive towards organic Hg compounds as compared to inorganic compounds regarding the endpoints cytotoxicity and barrier integrity. Whereas there are low transfer rates from the blood side to the CSF side, our results strongly indicate an active transfer of the organic mercury compounds out of the CSF. These results are the first to demonstrate an efflux of organic mercury compounds regarding the CNS and provide a completely new approach in the understanding of mercury compounds specific transport.}, language = {en} }