TY  - JOUR
A1  - Gerecke, Christian
A1  - Scholtka, Bettina
A1  - Loewenstein, Yvonne
A1  - Fait, Isabel
A1  - Gottschalk, Uwe
A1  - Rogoll, Dorothee
A1  - Melcher, Ralph
A1  - Kleuser, Burkhard
T1  - Hypermethylation of ITGA4, TFPI2 and VIMENTIN promoters is increased in inflamed colon tissue: putative risk markers for colitis-associated cancer
JF  - Journal of cancer research and clinical oncology : official organ of the Deutsche Krebsgesellschaft
N2  - Epigenetic silencing of tumor suppressor genes is involved in early transforming events and has a high impact on colorectal carcinogenesis. Likewise, colon cancers that derive from chronically inflamed bowel diseases frequently exhibit epigenetic changes. But there is little data about epigenetic aberrations causing colorectal cancer in chronically inflamed tissue. The aim of the present study was to evaluate the aberrant gain of methylation in the gene promoters of VIM, TFPI2 and ITGA4 as putative early markers in the development from inflamed tissue via precancerous lesions toward colorectal cancer.
 Initial screening of different cancer cell lines by using methylation-specific PCR revealed a putative colon cancer-specific methylation pattern. Additionally, a demethylation assay was performed to investigate the methylation-dependent gene silencing of ITGA4. The candidate markers were analyzed in colonic tissue specimens from patients with colorectal cancer (n = 15), adenomas (n = 76), serrated lesions (n = 13), chronic inflammation (n = 10) and normal mucosal samples (n = 9).
 A high methylation frequency of VIM (55.6 %) was observed in normal colon tissue, whereas ITGA4 and TFPI2 were completely unmethylated in controls. A significant gain of methylation frequency with progression of disease as well as an age-dependent effect was detectable for TFPI2. ITGA4 methylation frequency was high in precancerous and cancerous tissues as well as in inflammatory bowel diseases (IBD).
 The already established methylation marker VIM does not permit a specific and sensitive discrimination of healthy and neoplastic tissue. The methylation markers ITGA4 and TFPI2 seem to be suitable risk markers for inflammation-associated colon cancer.
KW  - Epigenetic
KW  - DNA methylation
KW  - Colon cancer
KW  - Colitis
KW  - Gastrointestinal tract
KW  - Biomarker
Y1  - 2015
U6  - https://doi.org/10.1007/s00432-015-1972-8
SN  - 0171-5216
SN  - 1432-1335
VL  - 141
IS  - 12
SP  - 2097
EP  - 2107
PB  - Springer
CY  - New York
ER  - 
TY  - JOUR
A1  - Schraplau, Anne
A1  - Schewe, Bettina
A1  - Neuschäfer-Rube, Frank
A1  - Ringel, Sebastian
A1  - Neuber, Corinna
A1  - Kleuser, Burkhard
A1  - Püschel, Gerhard Paul
T1  - Enhanced thyroid hormone breakdown in hepatocytes by mutual induction of the constitutive androstane receptor (CAR, NR1I3) and arylhydrocarbon receptor by benzo[a]pyrene and phenobarbital
JF  - Toxicology
N2  - Xenobiotics may interfere with the hypothalamic-pituitary-thyroid endocrine axis by inducing enzymes that inactivate thyroid hormones and thereby reduce the metabolic rate. This induction results from an activation of xeno-sensing nuclear receptors. The current study shows that benzo[a]pyrene, a frequent contaminant of processed food and activator of the arylhydrocarbon receptor (AhR) activated the promoter and induced the transcription of the nuclear receptor constitutive androstane receptor (CAR, NR1I3) in rat hepatocytes. Likewise, phenobarbital induced the AhR transcription. This mutual induction of the nuclear receptors enhanced the phenobarbital-dependent induction of the prototypic CAR target gene Cyp2b1 as well as the AhR-dependent induction of UDP-glucuronosyltransferases. In both cases, the induction by the combination of both xenobiotics was more than the sum of the induction by either substance alone. By inducing the AhR, phenobarbital enhanced the benzo[a]pyrene-dependent reduction of thyroid hormone half-life and the benzo[a]pyrene-dependent increase in the rate of thyroid hormone glucuronide formation in hepatocyte cultures. CAR ligands might thus augment the endocrine disrupting potential of AhR activators by an induction of the AhR. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
KW  - Endocrine disruption
KW  - Xenobesity
KW  - Aryl-hydrocarbon receptor
KW  - Cyp2b1
KW  - Thyroid hormone
KW  - UDP-glucuronosyltransferase
Y1  - 2015
U6  - https://doi.org/10.1016/j.tox.2014.12.004
SN  - 0300-483X
VL  - 328
SP  - 21
EP  - 28
PB  - Elsevier
CY  - Clare
ER  - 
TY  - JOUR
A1  - Sagu Tchewonpi, Sorel
A1  - Nso, Emmanuel Jong
A1  - Homann, Thomas
A1  - Kapseu, Cesar
A1  - Rawel, Harshadrai Manilal
T1  - Extraction and purification of beta-amylase from stems of Abrus precatorius by three phase partitioning
JF  - Food chemistry
N2  - The stems of Abrus precatorius were used to extract a beta-amylase enriched fraction. A three phase partitioning method and a Doehlert design with 3 variables (ratio of crude extract/t-butanol, the ammonium sulphate saturation and pH) were used. The data was fitted in a second-order polynomial model and the parameters were optimized to enrich beta-amylase. Experimental responses for the modulation were recovery of activity and the purification factor. The optimal conditions were: a ratio of crude extract/t-butanol of 0.87 (v/v), saturation in ammonium sulphate of 49.46% (w/v) and a pH of 5.2. An activity recovery of 156.2% and a purification factor of 10.17 were found. The enriched enzyme was identified as a beta-amylase and its molecular weight was 60.1 kDa. K-m and V-max values were 79.37 mg/ml and 5.13 U/ml, respectively and the highest activity was registered at a temperature of 70 degrees C and a pH between 6 and 6.5. A significant stabilization of the beta-amylase was observed up to 65 degrees C. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - Purification
KW  - Beta-amylase
KW  - Abrus precatorius
KW  - Three phase partitioning
KW  - Doehlert design
Y1  - 2015
U6  - https://doi.org/10.1016/j.foodchem.2015.03.028
SN  - 0308-8146
SN  - 1873-7072
VL  - 183
SP  - 144
EP  - 153
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Kana-Sop, Marie Modestine
A1  - Gouado, Inocent
A1  - Achu, Mercy Bih
A1  - Van Camp, John
A1  - Zollo, Paul Henri Amvam
A1  - Schweigert, Florian J.
A1  - Oberleas, Donald
A1  - Ekoe, Tetanye
T1  - The Influence of Iron and Zinc Supplementation on the Bioavailability of Provitamin A Carotenoids from Papaya Following Consumption of a Vitamin A-Deficient Diet
JF  - Journal of nutritional science and vitaminology
N2  - Iron deficiency anemia, zinc and vitamin A deficiencies are serious public health problems in Cameroon, as in many developing countries. Local vegetables which are sources of provitamin A carotenoids (PACs) can be used to improve vitamin A intakes. However, traditional meals are often unable to cover zinc and iron needs. The aim of this study was to determine the bioavailability of 3 PACs (alpha-carotene, beta-carotene, and beta-cryptoxanthin) in young men, who were fed with a vitamin A-free diet and received iron and zinc supplementation. Twelve healthy participants were divided into three groups and were supplemented with elemental iron (20 mg of iron fumarate), 20 mg of zinc sulfate or iron + zinc (20 mg of iron in the morning and 20 mg of zinc in the evening) for 11 d. They were given a vitamin A- and PAC-free diet from the 6th to the 11th day, followed by a test meal containing 0.55 kg of freshly peeled papaya as a source of PACs. Blood samples were collected four times successively on the 11th day (the test meal day), at TO (just after the test meal), after 2 h (T2), after 4 h (T4) and after 7 h (T7). Ultracentrifugation was used to isolate serum chylomicrons. Retinol appearance and PAC postprandial concentrations were determined. The supplementation with zinc, iron and iron+zinc influenced the chylomicron appearance of retinol and PACs differently as reflected by retention times and maximum absorption peaks. Iron led to highest retinol levels in the chylomicron. Zinc and iron+zinc supplements were best for optimal intact appearance of alpha-carotene, beta-carotene and beta-cryptoxanthin respectively. Supplementation with iron led to the greatest bioavailability of PACs from papaya and its conversion to retinol.
KW  - micronutrient deficiencies
KW  - zinc/iron supplementation
KW  - carotenoids bioavailability
KW  - Cameroon
Y1  - 2015
SN  - 0301-4800
SN  - 1881-7742
VL  - 61
IS  - 3
SP  - 205
EP  - 214
PB  - Univ. of Tokyo Pr.
CY  - Tokyo
ER  - 
TY  - JOUR
A1  - Danquah, Ina
A1  - Dobrucky, C. Lydia
A1  - Frank, Laura K.
A1  - Henze, Andrea
A1  - Amoako, Yaw A.
A1  - Bedu-Addo, George
A1  - Raila, Jens
A1  - Schulze, Matthias Bernd
A1  - Mockenhaupt, Frank P.
A1  - Schweigert, Florian J.
T1  - Vitamin A: potential misclassification of vitamin A status among patients with type 2 diabetes and hypertension in urban Ghana
JF  - The American journal of clinical nutrition : a publication of the American Society for Nutrition, Inc.
N2  - Background: Sub-Saharan Africa is facing a double burden of malnutrition: vitamin A deficiency (VAD) prevails, whereas the nutrition-related chronic conditions type 2 diabetes (T2D) and hypertension are emerging. Serum retinol a VAD marker increases in kidney disease and decreases in inflammation, which can partly be attributed to alterations in the vitamin A transport proteins retinol-binding protein 4 (RBP4) and prealbumin. Kidney dysfunction and inflammation commonly accompany T2D and hypertension.
 Objective: Among urban Ghanaians, we investigated the associations of T2D and hypertension with serum retinol as well as the importance of kidney function and inflammation in this regard.
 Design: A hospital-based, case-control study in individuals for risk factors of T2D, hypertension, or both was conducted in Kumasi, Ghana (328 controls, 197 with T2D, 354 with hypertension, and 340 with T2D plus hypertension). In 1219 blood samples, serum retinol, RBP4, and prealbumin were measured. Urinary albumin and estimated glomerular filtration rate (eGFR) defined kidney function. C-reactive protein (CRP) >5 mg/L indicated inflammation. We identified associations of T2D and hypertension with retinol by linear regression and calculated the contribution of RBP4, prealbumin, urinary albumin, eGFR, and CRP to these associations as the percentages of the explained variance of retinol.
 Results: VAD (retinol <1.05 mu mol/L) was present in 10% of this predominantly female, middle-aged, overweight, and deprived population. Hypertension, but not T2D, was positively associated with retinol (beta: 0.12; 95% CI: 0.08, 0,17), adjusted for age, sex, socioeconomic factors, anthropometric measurements, and lifestyle. In addition to RBP4 (72%) and prealbumin (22%), the effect of increased retinol on individuals with hypertension was mainly attributed to impaired kidney function (eGFR: 30%; urinary albumin: 5%) but not to inflammation.
 Conclusions: In patients with hypertension, VAD might be underestimated because of increased serum retinol in the context of kidney dysfunction. Thus, the interpretation of serum retinol in sub-Saharan Africa should account for hypertension status.
KW  - hypertension
KW  - inflammation
KW  - kidney dysfunction
KW  - type 2 diabetes
KW  - vitamin A deficiency
Y1  - 2015
U6  - https://doi.org/10.3945/ajcn.114.101345
SN  - 0002-9165
SN  - 1938-3207
VL  - 102
IS  - 1
SP  - 207
EP  - 214
PB  - American Society for Nutrition, Inc.
CY  - Bethesda
ER  - 
TY  - JOUR
A1  - Zirafi, Onofrio
A1  - Kim, Kyeong-Ae
A1  - Ständker, Ludger
A1  - Mohr, Katharina B.
A1  - Sauter, Daniel
A1  - Heigele, Anke
A1  - Kluge, Silvia F.
A1  - Wiercinska, Eliza
A1  - Chudziak, Doreen
A1  - Richter, Rudolf
A1  - Möpps, Barbara
A1  - Gierschik, Peter
A1  - Vas, Virag
A1  - Geiger, Hartmut
A1  - Lamla, Markus
A1  - Weil, Tanja
A1  - Burster, Timo
A1  - Zgraja, Andreas
A1  - Daubeuf, Francois
A1  - Frossard, Nelly
A1  - Hachet-Haas, Muriel
A1  - Heunisch, Fabian
A1  - Reichetzeder, Christoph
A1  - Galzi, Jean-Luc
A1  - Perez-Castells, Javier
A1  - Canales-Mayordomo, Angeles
A1  - Jimenez-Barbero, Jesus
A1  - Gimenez-Gallego, Guillermo
A1  - Schneider, Marion
A1  - Shorter, James
A1  - Telenti, Amalio
A1  - Hocher, Berthold
A1  - Forssmann, Wolf-Georg
A1  - Bonig, Halvard
A1  - Kirchhoff, Frank
A1  - Münch, Jan
T1  - Discovery and Characterization of an Endogenous CXCR4 Antagonist
JF  - Cell reports
N2  - CXCL12-CXCR4 signaling controls multiple physiological processes and its dysregulation is associated with cancers and inflammatory diseases. To discover as-yet-unknown endogenous ligands of CXCR4, we screened a blood-derived peptide library for inhibitors of CXCR4-tropic HIV-1 strains. This approach identified a 16 amino acid fragment of serum albumin as an effective and highly specific CXCR4 antagonist. The endogenous peptide, termed EPI-X4, is evolutionarily conserved and generated from the highly abundant albumin precursor by pH-regulated proteases. EPI-X4 forms an unusual lasso-like structure and antagonizes CXCL12-induced tumor cell migration, mobilizes stem cells, and suppresses inflammatory responses in mice. Furthermore, the peptide is abundant in the urine of patients with inflammatory kidney diseases and may serve as a biomarker. Our results identify EPI-X4 as a key regulator of CXCR4 signaling and introduce proteolysis of an abundant precursor protein as an alternative concept for chemokine receptor regulation.
Y1  - 2015
U6  - https://doi.org/10.1016/j.celrep.2015.03.061
SN  - 2211-1247
VL  - 11
IS  - 5
SP  - 737
EP  - 747
PB  - Cell Press
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Maschirow, Laura
A1  - Khalaf, Kinda
A1  - Al-Aubaidy, Hayder A.
A1  - Jelinek, Herbert F.
T1  - Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes - Biomarkers as a possible tool for early disease detection for rural screening
JF  - Clinical biochemistry : official journal of the Canadian Society of Clinical Chemists
N2  - Objectives: This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes.
 Design and methods: Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects.
 Results: While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant.
 Conclusions: The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings. (C) 2015 The Authors. The Canadian Society of Clinical Chemists. Published by Elsevier Inc.
KW  - Prediabetes
KW  - Oxidative stress
KW  - Inflammation
KW  - Coagulation
KW  - Endothelial dysfunction
Y1  - 2015
U6  - https://doi.org/10.1016/j.clinbiochem.2015.02.015
SN  - 0009-9120
SN  - 1873-2933
VL  - 48
IS  - 9
SP  - 581
EP  - 585
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Satwiko, Muhammad Gahan
A1  - Ikeda, Koji
A1  - Nakayama, Kazuhiko
A1  - Yagi, Keiko
A1  - Hocher, Berthold
A1  - Hirata, Ken-Ichi
A1  - Emoto, Noriaki
T1  - Targeted activation of endothelin-1 exacerbates hypoxia-induced pulmonary hypertension
JF  - Biochemical and biophysical research communications
N2  - Pulmonary arterial hypertension (PAH) is a fatal disease that eventually results in right heart failure and death. Current pharmacologic therapies for PAH are limited, and there are no drugs that could completely cure PAH. Enhanced activity of endothelin system has been implicated in PAH severity and endothelin receptor antagonists have been used clinically to treat PAH. However, there is limited experimental evidence on the direct role of enhanced endothelin system activity in PAL-I. Here, we investigated the correlation between endothelin-1 (ET-1) and PAH using ET-1 transgenic (ETTG) mice. Exposure to chronic hypoxia increased right ventricular pressure and pulmonary arterial wall thickness in ETTG mice compared to those in wild type mice. Of note, ETTG mice exhibited modest but significant increase in right ventricular pressure and vessel wall thickness relative to wild type mice even under normoxic conditions. To induce severe PAH, we administered SU5416, a vascular endothelial growth factor receptor inhibitor, combined with exposure to chronic hypoxia. Treatment with SU5416 modestly aggravated hypoxia-induced pulmonary hypertension, right ventricular hypertrophy, and pulmonary arterial vessel wall thickening in ETTG mice in association with increased interleukin-6 expression in blood vessels. However, there was no sign of obliterative endothelial cell proliferation and plexiform lesion formation in the lungs. These results demonstrated that enhanced endothelin system activity could be a causative factor in the development of PAH and provided rationale for the inhibition of endothelin system to treat PAH. (C) 2015 Elsevier Inc. All rights reserved.
KW  - Pulmonary arterial hypertension
KW  - Endothelin
KW  - Hypoxia
KW  - SU5416
Y1  - 2015
U6  - https://doi.org/10.1016/j.bbrc.2015.08.002
SN  - 0006-291X
SN  - 1090-2104
VL  - 465
IS  - 3
SP  - 356
EP  - 362
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Fruscalzo, Arrigo
A1  - Londero, Ambrogio P.
A1  - Driul, Lorenza
A1  - Henze, Andrea
A1  - Tonutti, Laura
A1  - Ceraudo, Maria
A1  - Zanotti, Giuseppe
A1  - Berni, Rodolfo
A1  - Schweigert, Florian J.
A1  - Raila, Jens
T1  - First trimester concentrations of the TTR-RBP4-retinol complex components as early markers of insulin-treated gestational diabetes mellitus
JF  - Clinical chemistry and laboratory medicine : journal of the Forum of the European Societies of Clinical Chemistry - the European Branch of the International Federation of Clinical Chemistry and Laboratory Medicine
N2  - Background: The objective of the study was to investigate the relationship between first trimester maternal serum levels of the TTR-RBP4-ROH complex components and the later insurgence of an altered glucose metabolism during pregnancy.
 Methods: Retrospective case control study including 96 patients between the 12th and 14th week of gestation, 32 that developed gestational diabetes mellitus (GDM), respectively, 21 non-insulin-treated (dGDM) and 11 insulin-treated (iGDM), 20 large for gestational age fetuses (LGA) without GDM and 44 patients with normal outcome as control. Serum concentrations of RBP4 and TTR were assessed by ELISA; serum concentration of ROH by reverse-phase high performance liquid chromatography (rpHPLC). The molecular heterogeneity of TTR and RBP4 was analyzed after immunoprecipitation by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).
 Results: iGDM patients were characterized by reduced TTR, RBP4 and ROH compared to controls (respectively, iGDM vs. controls, mean +/- SD: TTR 3.96 +/- 0.89 mu mol/L vs. 4.68 +/- 1.21 mu mol/L, RBP4 1.13 +/- 0.25 mu mol/L vs. 1.33 +/- 0.38 mu mol/L and ROH 1.33 +/- 0.17 mu mol/L vs. 1.62 +/- 0.29 mu mol/L, p < 0.05). TTR containing Gly10 in place of Cys10 was lower in the iGDM group (p < 0.05) compared to controls. In the final logistic regression model ROH significantly predicted the diagnosis of iGDM (OR 0.93, 95% CI 0.87-0.98, p < 0.05).
 Conclusions: First trimester maternal serum ROH, RBP4 and TTR represent potential biomarkers associated with the development of iGDM.
KW  - first trimester
KW  - gestational diabetes mellitus (GDM)
KW  - insulin
KW  - large for gestational age fetus (LGA)
KW  - protein microheterogeneity
KW  - retinol (ROH)
KW  - serum retinol binding protein (RBP4)
KW  - transthyretin (TTR)
Y1  - 2015
U6  - https://doi.org/10.1515/cclm-2014-0929
SN  - 1434-6621
SN  - 1437-4331
VL  - 53
IS  - 10
SP  - 1643
EP  - 1651
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Luckert, Claudia
A1  - Hessel, Stefanie
A1  - Lenze, Dido
A1  - Lampen, Alfonso
T1  - Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis
JF  - Toxicology in vitro
N2  - 1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 mu M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a vertical bar fold change vertical bar of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NF kappa B and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR alpha/gamma/delta were predicted to be inhibited.
 In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - Pyrrolizidine alkaloids
KW  - Transcriptomics
KW  - Gene expression
KW  - Hepatotoxicity
Y1  - 2015
U6  - https://doi.org/10.1016/j.tiv.2015.06.021
SN  - 0887-2333
VL  - 29
IS  - 7
SP  - 1669
EP  - 1682
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Niehoff, Ann-Christin
A1  - Bauer, Oliver Bolle
A1  - Kröger, Sabrina
A1  - Fingerhut, Stefanie
A1  - Schulz, Jacqueline
A1  - Meyer, Sören
A1  - Sperling, Michael
A1  - Jeibmann, Astrid
A1  - Schwerdtle, Tanja
A1  - Karst, Uwe
T1  - Quantitative Bioimaging to Investigate the Uptake of Mercury Species in Drosophila melanogaster
JF  - Analytical chemistry
N2  - The uptake of mercury species in the model organism Drosophila melanogaster was investigated by elemental bioimaging using laser ablation-inductively coupled plasma mass spectrometry (LA-ICPMS). The mercury distribution in Drosophila melanogaster was analyzed for the three species mercury(II) chloride, methylmercury chloride, and thimerosal after intoxication. A respective analytical method was developed and applied to the analysis of the entire Drosophila melanogaster first, before a particular focus was directed to the cerebral areas of larvae and adult flies. For quantification of mercury, matrix-matched standards based on gelatin were prepared. Challenges of spatially dissolved mercury determination, namely, strong evaporation issues of the analytes and an inhomogeneous distribution of mercury in the standards due to interactions with cysteine containing proteins of the gelatin were successfully addressed by complexation with meso-2,3-dimercaptosuccinic acid (DMSA). No mercury was detected in the cerebral region for mercury(II) chloride, whereas both organic species showed the ability to cross the blood brain barrier. Quantitatively, the mercury level in the brain exceeded the fed concentration indicating mercury enrichment, which was approximately 3 times higher for methylmercury chloride than for thimerosal.
Y1  - 2015
U6  - https://doi.org/10.1021/acs.analchem.5b02500
SN  - 0003-2700
SN  - 1520-6882
VL  - 87
IS  - 20
SP  - 10392
EP  - 10396
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Luckert, Claudia
A1  - Hessel, Stefanie
A1  - Lampen, Alfonso
A1  - Braeuning, Albert
T1  - Utility of an appropriate reporter assay: Heliotrine interferes with GAL4/upstream activation sequence-driven reporter gene systems
JF  - Analytical biochemistry : methods in the biological sciences
N2  - Reporter gene assays are widely used for the assessment of transcription factor activation following xenobiotic exposure of cells. A critical issue with such assays is the possibility of interference of test compounds with the test system, for example, by direct inhibition of the reporter enzyme. Here we show that the pyrrolizidine alkaloid heliotrine interferes with reporter signals derived from GAL4-based nuclear receptor transactivation assays by a mechanism independent of luciferase enzyme inhibition. These data highlight the necessity to conduct proper control experiments in order to avoid perturbation of reporter assays by test chemicals. (C) 2015 Elsevier Inc. All rights reserved.
KW  - Firefly luciferase inhibition
KW  - Nuclear receptor
KW  - Transactivation assay
Y1  - 2015
U6  - https://doi.org/10.1016/j.ab.2015.07.009
SN  - 0003-2697
SN  - 1096-0309
VL  - 487
SP  - 45
EP  - 48
PB  - Elsevier
CY  - San Diego
ER  - 
TY  - JOUR
A1  - Meyer, Sören
A1  - Raber, Georg
A1  - Ebert, Franziska
A1  - Taleshi, Mojtaba S.
A1  - Francesconi, Kevin A.
A1  - Schwerdtle, Tanja
T1  - Arsenic-containing hydrocarbons and arsenic-containing fatty acids: Transfer across and presystemic metabolism in the Caco-2 intestinal barrier model
JF  - Molecular nutrition & food research : bioactivity, chemistry, immunology, microbiology, safety, technology
N2  - Scope: Arsenic-containing hydrocarbons (AsHCs) and arsenic-containing fatty acids (AsFAs) represent two classes of arsenolipids occurring naturally in marine food. Toxicological data are yet scarce and an assessment regarding the risk to human health has not been possible. Here, we investigated the transfer and presystemic metabolism of five arsenolipids in an intestinal barrier model.
 Methods and results: Three AsHCs and two AsFAs were applied to the Caco-2 intestinal barrier model. Thereby, the short-chain AsHCs reached up to 50% permeability. Transport is likely to occur via passive diffusion. The AsFAs showed lower intestinal bioavailability, but respective permeabilities were still two to five times higher as compared to arsenobetaine or arsenosugars. Interestingly, AsFAs were effectively biotransformed while passing the in vitro intestinal barrier, whereas AsHCs were transported to the blood-facing compartment essentially unchanged.
 Conclusion: AsFAs can be presystemically metabolised and the amount of transferred arsenic is lower than that for AsHCs. In contrast, AsHCs are likely to be highly intestinally bioavailable to humans. Since AsHCs exert strong toxicity in vitro and in vivo, toxicity studies with experimental animals as well as a human exposure assessment are needed to assess the risk to human health related to the presence of AsHCs in seafood.
KW  - Arsenolipids
KW  - Caco-2 intestinal barrier model
KW  - Presystemic metabolism
KW  - Toxicity
Y1  - 2015
U6  - https://doi.org/10.1002/mnfr.201500286
SN  - 1613-4125
SN  - 1613-4133
VL  - 59
IS  - 10
SP  - 2044
EP  - 2056
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Reichel, Martin
A1  - Hoenig, Stefanie
A1  - Liebisch, Gerhard
A1  - Lüth, Anja
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Schmitz, Gerd
A1  - Kornhuber, Johannes
T1  - Alterations of plasma glycerophospholipid and sphingolipid species in male alcohol-dependent patients
JF  - Biochimica et biophysica acta : Molecular and cell biology of lipids
N2  - Background: Alcohol abuse is a major risk factor for somatic and neuropsychiatric diseases. Despite their potential clinical importance, little is known about the alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species associated with alcohol abuse.
 Methods: Plasma GPL and SPL species were quantified using electrospray ionization tandem mass spectrometry in samples from 23 male alcohol-dependent patients before and after detoxification, as well as from 20 healthy male controls.
 Results: A comparison of alcohol-dependent patients with controls revealed higher phosphatidylcholine (PC; P-value = 0.008) and phosphatidylinositol (PI; P-value = 0.001) concentrations in patients before detoxification, and higher PI (P-value = 0.001) and phosphatidylethanolamine (PE)-based plasmalogen (PEP; P-value = 0.003) concentrations after detoxification. Lysophosphatidylcholines (LPC) were increased by acute intoxication (P-value = 0.002). Sphingomyelin (SM) concentration increased during detoxification (P-value = 0.011). The concentration of SM 23:0 was lower in patients (P-value = 2.79 x 10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer d18:1/18:0 were higher in patients (P-value = 2.45 x 10(-5) and 3.73 x 10(-5)). Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated positively with the concentrations of eight LPC species, while activity of secreted ASM was inversely correlated with several PE, PI and PC species, and positively correlated with the molar ratio of PC to SM (Pearson's r = 0.432; P-value = 0.039).
 Conclusion: Plasma concentrations of numerous GPL and SPL species were altered in alcohol-dependent patients. These molecules might serve as potential biomarkers to improve the diagnosis of patients and to indicate health risks associated with alcohol abuse. Our study further indicates that there are strong interactions between plasma GPL concentrations and SPL metabolism. (C) 2015 Elsevier B.V. All rights reserved.
KW  - Acid sphingomyelinase
KW  - Alcohol dependence
KW  - Anxiety
KW  - Cardiovascular
KW  - Case-control study
KW  - Ceramide
KW  - Clinical
KW  - Depression
KW  - Diagnostic
KW  - Disease
KW  - Glycerophospholipids
KW  - Lysophosphatidylcholines
KW  - Mass spectrometry
KW  - Phosphatidylcholines
KW  - Phosphatidylinositols
KW  - Plasma
KW  - Plasmalogens
KW  - Sphingolipids
KW  - Sphingomyelin
KW  - Tandem mass spectrometry
Y1  - 2015
U6  - https://doi.org/10.1016/j.bbalip.2015.08.005
SN  - 1388-1981
SN  - 0006-3002
VL  - 1851
IS  - 11
SP  - 1501
EP  - 1510
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Reinkensmeier, Annika
A1  - Bassler, Sara
A1  - Schlueter, Oliver
A1  - Rohn, Sascha
A1  - Rawel, Harshadrai Manilal
T1  - Characterization of individual proteins in pea protein isolates and air classified samples
JF  - Food research international
N2  - Generally, pea proteins are extracted at comparatively acidic or basic pH values to provide a basis for protein isolate production. Such processing steps result in partial denaturation of the proteins rendering them in most cases insoluble at food processing pH conditions and limiting their application in food products. Here, the comparison of the solubility properties of pea proteins in protein enriched fractions deriving from air classification is reported. Protein content, solubility, and physicochemical parameters of different fractions of the pea (Pisum sativum) variety 'Salamanca' were investigated as a function of pH using SDS-PAGE and surface hydrophobicity. Whole pea flour (20% protein), air classified, protein-enriched pea flour (48% protein), pea flour made from hulls (2.8% protein), and pea protein isolate (81% protein) served as test materials. Fractionation and pH value affected the composition and surface hydrophobicity of the proteins as well as the content of trypsin inhibitors. All samples showed a high buffering capacity in the range of pH 4 to 10. The direct comparison documents the comparatively better protein quality of the air classified, protein enriched pea fraction. The solubility of the pea protein isolate can be improved by using selected additives, giving new possibilities for plant protein application. Relevant technofunctional properties were determined and compared with two commercially available pea-based products (whole pea flour and an isolate). Water binding capacity was highest for the commercially available pea flour followed by the pea hull flour. Fat binding capacity remained more or less unchanged. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - Pea flour
KW  - Pea protein isolate
KW  - Extraction
KW  - Physicochemical properties
KW  - Technofunctional properties
Y1  - 2015
U6  - https://doi.org/10.1016/j.foodres.2015.05.009
SN  - 0963-9969
SN  - 1873-7145
VL  - 76
SP  - 160
EP  - 167
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Groop, Per-Henrik
A1  - Cooper, Mark E.
A1  - Perkovic, Vlado
A1  - Sharma, Kumar
A1  - Schernthaner, Guntram
A1  - Haneda, Masakazu
A1  - Hocher, Berthold
A1  - Gordat, Maud
A1  - Cescutti, Jessica
A1  - Woerle, Hans-Juergen
A1  - von Eynatten, Maximilian
T1  - Dipeptidyl peptidase-4 inhibition with linagliptin and effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction: Rationale and design of the MARLINA-T2D trial
JF  - Diabetes & vascular disease research : official journal of the International Society of Diabetes and Vascular Disease
N2  - Efficacy, Safety & Modification of Albuminuria in Type 2 Diabetes Subjects with Renal Disease with LINAgliptin (MARLINA-T2D), a multicentre, multinational, randomized, double-blind, placebo-controlled, parallel-group, phase 3b clinical trial, aims to further define the potential renal effects of dipeptidyl peptidase-4 inhibition beyond glycaemic control. A total of 350 eligible individuals with inadequately controlled type 2 diabetes and evidence of renal disease are planned to be randomized in a 1:1 ratio to receive either linagliptin 5mg or placebo in addition to their stable glucose-lowering background therapy for 24weeks. Two predefined main endpoints will be tested in a hierarchical manner: (1) change from baseline in glycated haemoglobin and (2) time-weighted average of percentage change from baseline in urinary albumin-to-creatinine ratio. Both endpoints are sufficiently powered to test for superiority versus placebo after 24weeks with =0.05. MARLINA-T2D is the first of its class to prospectively explore both the glucose- and albuminuria-lowering potential of a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes and evidence of renal disease.
KW  - Dipeptidyl peptidase-4 inhibition
KW  - linagliptin
KW  - type 2 diabetes
KW  - chronic kidney disease
KW  - glycaemic control
KW  - albuminuria
Y1  - 2015
U6  - https://doi.org/10.1177/1479164115579002
SN  - 1479-1641
SN  - 1752-8984
VL  - 12
IS  - 6
SP  - 455
EP  - 462
PB  - Sage Publ.
CY  - London
ER  - 
TY  - JOUR
A1  - Baier, Daniel
A1  - Purschke, Benedict
A1  - Schmitt, Christophe
A1  - Rawel, Harshadrai Manilal
A1  - Knorr, Dietrich
T1  - Effect of high pressure - low temperature treatments on structural characteristics of whey proteins and micellar caseins
JF  - Food chemistry
N2  - In this study, structural changes in micellar caseins and whey proteins due to high pressure - low temperature treatments (HPLT) were investigated and compared to changes caused by high pressure treatments at room temperature. Whey protein isolate (WPI) solutions as well as micellar casein (MC) dispersions and mixtures were treated at 500 MPa (pH 7.0 and 5.8) at room temperature, -15 degrees C and -35 degrees C. Surface hydrophobicity and accessible thiol groups remained nearly unchanged after HPLT treatments whereas HP treatments at room temperature caused an unfolding of the WPI, resulting in an increase in surface hydrophobicity and exposure of the thiol groups. For HPLT treatments, distinct changes in the secondary structure (increase in the amount of beta-sheets) were observed while the tertiary structure remained unchanged. Large flocs, stabilized by hydrophobic interactions and hydrogen bonds, were formed in casein containing samples due to HPLT treatments. Depending on the pH and the applied HPLT treatment parameters, these interactions differed significantly from the interactions determined in native micelles. (C) 2015 Elsevier Ltd. All rights reserved.
KW  - High pressure - low temperature treatments
KW  - Whey proteins
KW  - Micellar caseins
KW  - Structural changes
Y1  - 2015
U6  - https://doi.org/10.1016/j.foodchem.2015.04.049
SN  - 0308-8146
SN  - 1873-7072
VL  - 187
SP  - 354
EP  - 363
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Schmidt, Alexander
A1  - Pourteau, Amaury
A1  - Candan, Osman
A1  - Oberhänsli, Roland
T1  - Lu-Hf geochronology on cm-sized garnets using microsampling: New constraints on garnet growth rates and duration of metamorphism during continental collision (Menderes Massif, Turkey)
JF  - Earth & planetary science letters
N2  - This study shows Lu-Hf geochronology of zoned garnet crystals contained in mica schists from the southern Menderes Massif, Turkey. Selected samples are four 3-5 cm large garnet megacrysts of which several consecutive garnet shells have been sampled with a micro-saw and analyzed for dating. The results are used to extract growth rates of garnet, and also to improve the time constraint for Alpine-aged overprint of the Pan-African basement in the Menderes Massif.
 The new data provides a precise age determination for prograde Barrovian metamorphism in the southern Menderes Massif, which so far was placed between 63 and 27 Ma on the basis of mica Rb-Sr and Ar-Ar dating. This study provides new constraints crucial to the understanding of the tectonic evolution of southwest Anatolia and the Aegean realm, as it yields a shorter outline for Alpine aged continental collision.
KW  - Lu-Hf geochronology
KW  - garnet
KW  - Alpine metamorphism
KW  - Menderes Massif
Y1  - 2015
U6  - https://doi.org/10.1016/j.epsl.2015.09.015
SN  - 0012-821X
SN  - 1385-013X
VL  - 432
SP  - 24
EP  - 35
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Draude, Felix
A1  - Körsgen, Martin
A1  - Pelster, Andreas
A1  - Schwerdtle, Tanja
A1  - Müthing, Johannes
A1  - Arlinghaus, Heinrich F.
T1  - Characterization of freeze-fractured epithelial plasma membranes on nanometer scale with ToF-SIMS
JF  - Analytical & bioanalytical chemistry
N2  - Time-of-flight secondary ion mass spectrometry (ToF-SIMS) was used to characterize the freeze-fracturing process of human epithelial PANC-1 and UROtsa cells. For this purpose, phosphatidylcholine, sphingomyelin, phosphatidylethanolamine, and phosphatidylserine standard samples were investigated to find specific signals with both high specificity and signal intensity. The results were used to investigate single cells of subconfluent cell layers prepared with a special silicon wafer sandwich preparation technique. This freeze-fracturing technique strips cell membranes off the cells, isolating them on opposing silicon wafer substrates. Criteria were found for defining regions with stripped off cell membranes and, on the opposing wafer, complementary regions with the remaining cells. Measured ethanolamine/choline and serine/choline ratios in these regions clearly showed that in the freeze-fracturing process, the lipid bilayer of the plasma membrane is split along its central zone. Accordingly, only the outer lipid monolayer is stripped off the cell, while the inner lipid monolayer remains attached to the cell on the opposing wafer, thus allowing detailed analysis of a single lipid monolayer. Furthermore, it could be shown that using different washing procedures did not influence the transmembrane lipid distribution. Under optimized preparation conditions, it became feasible to detect lipids with a lateral resolution of approximately 100 nm. The data indicate that ToF-SIMS would be a very useful technique to study with very high lateral resolution changes in lipid composition caused, for example, by lipid storage diseases or pharmaceuticals that interfere with the lipid metabolism.
KW  - ToF-SIMS imaging
KW  - Life science
KW  - Lipid
KW  - Freeze-fracturing
KW  - Membrane
KW  - Transmembrane asymmetry
Y1  - 2015
U6  - https://doi.org/10.1007/s00216-014-8334-2
SN  - 1618-2642
SN  - 1618-2650
VL  - 407
IS  - 8
SP  - 2203
EP  - 2211
PB  - Springer
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Tsuprykov, Oleg
A1  - Chaykovska, Lyubov
A1  - Kretschmer, Axel
A1  - Stasch, Johannes-Peter
A1  - Pfab, Thiemo
A1  - Krause-Relle, Katharina
A1  - Reichetzeder, Christoph
A1  - Kalk, Philipp
A1  - Adamski, Jerzy
A1  - Hocher, Berthold
T1  - Endothelin-1 overexpression improves renal function in eNOS knockout mice
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background/Aims: To investigate the renal phenotype under conditions of an activated renal ET-1 system in the status of nitric oxide deficiency, we compared kidney function and morphology in wild-type, ET-1 transgenic (ET+/+), endothelial nitric oxide synthase knockout (eNOS-/-) and ET+/+eNOS-/- mice. Methods: We assessed blood pressure, parameters of renal morphology, plasma cystatin C, urinary protein excretion, expression of genes associated with glomerular filtration barrier and tissue remodeling, and plasma metabolites using metabolomics. Results: eNOS-/- and ET+/+eNOS-/- mice developed hypertension. Osteopontin, albumin and protein excretion were increased in eNOS-/- and restored in ET+/+eNOS-/- animals. All genetically modified mice developed renal interstitial fibrosis and glomerulosclerosis. Genes involved in tissue remodeling (serpinel, TIMP1, Collal, CCL2) were up-regulated in eNOS-/-, but not in ET+/+eNOS-/- mice. Plasma levels of free carnitine and acylcarnitines, amino acids, diacyl phosphatidylcholines, lysophosphatidylcholines and hexoses were descreased in eNOS-/- and were in the normal range in ET+/+eNOS-/- mice. Conclusion: eNOS-/- mice developed renal dysfunction, which was partially rescued by ET-1 overexpression in eNOS-/- mice. The metabolomics results suggest that ET-1 overexpression on top of eNOS knockout is associated with a functional recovery of mitochondria (rescue effect in 13-oxidation of fatty acids) and an increase in antioxidative properties (normalization of monounsaturated fatty acids levels). (C) 2015 The Author(s) Published by S. Karger AG, Basel
KW  - Chronic kidney disease
KW  - Endothelial nitric oxide synthase
KW  - Endothelin
KW  - Mice
KW  - Nitric oxide
Y1  - 2015
U6  - https://doi.org/10.1159/000438516
SN  - 1015-8987
SN  - 1421-9778
VL  - 37
IS  - 4
SP  - 1474
EP  - 1490
PB  - Karger
CY  - Basel
ER  -