TY  - JOUR
A1  - Yang, Fang
A1  - Lai, Xinlong
A1  - Deng, Li
A1  - Liu, Xiaoxiao
A1  - Li, Jian
A1  - Zeng, Shuixiu
A1  - Zhang, Cheng
A1  - Hocher, Carl-Friedrich
A1  - Hocher, Berthold
T1  - Association of endothelin-1 gene polymorphisms with the clinical phenotype in primary nephrotic syndrome of children
JF  - Life sciences : molecular, cellular and functional basis of therapy
N2  - Aims:This study aims to investigate the relationship between plasma endothelin-1 (ET-1) concentrations, ET-1 gene polymorphisms in loci rs5370, rs1630736, 3A/4A and clinical features of primary nephrotic syndrome (NS) in children.
 Materials and methods: Thirty-six children with primary NS were selected as case group, and 94 healthy children were selected as control group. All subjects were genotyped for three single nucleotide polymorphisms (SNPs) (rs5370, rs10478694 [3A4A) and rs 1630736) in the ET-1 gene by gene sequencing. The plasma ET-1 concentrations were measured using a radio-immunoassay.
 Key findings: Plasma ET-1 concentrations were higher in NS patients (P = 0.007) as compared to healthy children. The allele frequencies between control and NS patients were significantly different only with respect to the rs10478694 SNP of the ET-1 gene. The allele frequencies between control and NS patients for the rs5370 SNP showed a trend towards difference (P = 0.057). Plasma cholesterol in NS patients is associated with both: the Cl genotype in locus rs5370 and the 3A4A genotype in locus rs10478694 (P < 0.05 in both cases).
 Significance: The ET systems might play a disease modifying role in pediatric NS. Plasma cholesterol, a hallmark of NS. seems to be associated with genetic variations within the human ET-1 gene. (C) 2014 Elsevier Inc. All rights reserved.
KW  - Endothelin-1
KW  - Gene polymorphism
KW  - Childhood nephrotic syndrome
KW  - Cholesterol
Y1  - 2014
U6  - https://doi.org/10.1016/j.lfs.2014.04.010
SN  - 0024-3205
SN  - 1879-0631
VL  - 118
IS  - 2
SP  - 446
EP  - 450
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Yamamoto, Masayoshi
A1  - Baldermann, Susanne
A1  - Yoshikawa, Keisuke
A1  - Fujita, Akira
A1  - Mase, Nobuyuki
A1  - Watanabe, Naoharu
T1  - Determination of volatile compounds in four commercial samples of japanese green algae using solid phase microextraction gas chromatography mass spectrometry
JF  - The ScientificWorld journal
N2  - Green algae are of great economic importance. Seaweed is consumed fresh or as seasoning in Japan. The commercial value is determined by quality, color, and flavor and is also strongly influenced by the production area. Our research, based on solid phase microextraction gas chromatography mass spectrometry (SPME-GC-MS), has revealed that volatile compounds differ intensely in the four varieties of commercial green algae. Accordingly, 41 major volatile compounds were identified. Heptadecene was the most abundant compound from Okayama (Ulva prolifera), Tokushima (Ulva prolifera), and Ehime prefecture (Ulva linza). Apocarotenoids, such as ionones, and their derivatives were prominent volatiles in algae from Okayama (Ulva prolifera) and Tokushima prefecture (Ulva prolifera). Volatile, short chained apocarotenoids are among the most potent flavor components and contribute to the flavor of fresh, processed algae, and algae-based products. Benzaldehyde was predominant in seaweed from Shizuoka prefecture (Monostroma nitidum). Multivariant statistical analysis (PCA) enabled simple discrimination of the samples based on their volatile profiles. This work shows the potential of SPME-GC-MS coupled with multivariant analysis to discriminate between samples of different geographical and botanical origins and form the basis for development of authentication methods of green algae products, including seasonings.
Y1  - 2014
U6  - https://doi.org/10.1155/2014/289780
SN  - 1537-744X
PB  - Hindawi Publishing Corp.
CY  - New York
ER  - 
TY  - JOUR
A1  - Vignon-Zellweger, Nicolas
A1  - Relle, Katharina
A1  - Rahnenfuehrer, Jan
A1  - Schwab, Karima
A1  - Hocher, Berthold
A1  - Theuring, Franz
T1  - Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice
JF  - Life sciences : molecular, cellular and functional basis of therapy
N2  - Aims: The nitric oxide and endothelin systems are key components of a local paracrine hormone network in the heart. We previously reported that diastolic dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS-/-) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have been reported in both ET-1 and NO systems. Particularly, eNOS-/- mice present sex related phenotypic differences.
 Main methods: We used the ET-1 transgenic (ET+/+), eNOS-/-, and crossbred ET+/+ eNOS-/- mice, and wild type controls. We measured cardiac function by heart catheterization. Cardiac ventricles were collected for histological and molecular profiling.
 Key findings: We report here that (i) the level of ET-1 expression in eNOS-/- mice was elevated in males but not in females. (ii) Left ventricular end-diastolic blood pressure was higher in male eNOS-/- mice than in females. (ii) eNOS-/- males but not females developed cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intra-cardiac arteries developed in female ET+/+ and eNOS-/- mice but not in males. Additionally, (v) the cardiac expression of metalloprotease-9 was higher in eNOS-/- males compared to females. Finally, (vi) cardiac proteome analysis revealed that the protein abundance of the oxidative stress related enzyme superoxide dismutase presented with sexual dimorphism in eNOS-/- and ET+/+ mice.
 Significance: These results indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout mice are sex specific. Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases. (C) 2013 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
KW  - Endothelin-1
KW  - Nitric oxide
KW  - Cardiac function
KW  - Sexual dimorphism
Y1  - 2014
U6  - https://doi.org/10.1016/j.lfs.2013.12.003
SN  - 0024-3205
SN  - 1879-0631
VL  - 118
IS  - 2
SP  - 219
EP  - 225
PB  - Elsevier
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Unterberg, Marlies
A1  - Leffers, Larissa
A1  - Huebner, Florian
A1  - Humpf, Hans-Ulrich
A1  - Lepikhov, Konstantin
A1  - Walter, Joern
A1  - Ebert, Franziska
A1  - Schwerdtle, Tanja
T1  - Toxicity of arsenite and thio-DMA(V) after long-term (21 days) incubation of human urothelial cells: cytotoxicity, genotoxicity and epigenetics
JF  - Toxicology research
N2  - This study aims to further mechanistically understand toxic modes of action after chronic inorganic arsenic exposure. Therefore long-term incubation studies in cultured cells were carried out, to display chronically attained changes, which cannot be observed in the generally applied in vitro short-term incubation studies. Particularly, the cytotoxic, genotoxic and epigenetic effects of an up to 21 days incubation of human urothelial (UROtsa) cells with pico- to nanomolar concentrations of iAs(III) and its metabolite thio-DMA(V) were compared. After 21 days of incubation, cytotoxic effects were strongly enhanced in the case of iAs(III) and might partly be due to glutathione depletion and genotoxic effects on the chromosomal level. These results are in strong contrast to cells exposed to thio-DMA(V). Thus, cells seemed to be able to adapt to this arsenical, as indicated among others by an increase in the cellular glutathione level. Most interestingly, picomolar concentrations of both iAs(III) and thio-DMA(V) caused global DNA hypomethylation in UROtsa cells, which was quantified in parallel by 5-medC immunostaining and a newly established, reliable, high resolution mass spectrometry (HRMS)-based test system. This is the first time that epigenetic effects are reported for thio-DMA(V); iAs(III) induced epigenetic effects occur in at least 8000 fold lower concentrations as reported in vitro before. The fact that both arsenicals cause DNA hypomethylation at really low, exposure-relevant concentrations in human urothelial cells suggests that this epigenetic effect might contribute to inorganic arsenic induced carcinogenicity, which for sure has to be further investigated in future studies.
Y1  - 2014
U6  - https://doi.org/10.1039/c4tx00036f
SN  - 2045-452X
SN  - 2045-4538
VL  - 3
IS  - 6
SP  - 456
EP  - 464
PB  - Royal Society of Chemistry
CY  - Cambridge
ER  - 
TY  - JOUR
A1  - Uhr, Linda
A1  - Buchholz, Tina
A1  - Homann, Thomas
A1  - Huschek, Gerd
A1  - Rawel, Harshadrai Manilal
T1  - Targeted proteomics-based analysis of technical enzymes from fungal origin in baked products
JF  - Journal of cereal science
N2  - The application of technical enzymes is a potential tool in modulating the dough and baking quality of cereal products. No endogenous amylases (alpha- and beta-forms) are present in mature wheat grains; they may be synthesized or activated during germination. Hence, microbial alpha-amylases are added to the dough, being resistant to the endogenous alpha-amylase/trypsin inhibitors. Here, we report on the initial identification of two technical enzymes from a commercial sample based on an in-gel tryptic digestion coupled with MALDI-MS analysis. The primary component of the protein fraction with 51.3 kDa was alpha-amylase from Aspergillus species. A second major protein with 24.8 kDa was identified as endo-1,4-xylanase from Thermomyces lanuginosus. In the following experimental work up, a targeted proteomics approach utilizing the combination of specific proteolytic digestion of the added amylase and xylanase in wheat flour, dough or baked products, solid phase extraction of released peptides and their detection using LC-MS/MS was optimized. The targeted (MRM) MS/MS peptide signals showed that the peptide "ALSSALHER" (MW = 983) originating from amylase and "GWNPGLNAR" (MW = 983) from xylanase can be used to identify the corresponding technical enzymes added. Consequently, locally available baked products were tested and found to contain these enzymes as supplementary ingredients. (C) 2014 Elsevier Ltd. All rights reserved.
KW  - Technical enzymes
KW  - Amylase
KW  - Xylanase
KW  - Mass spectrometry
Y1  - 2014
U6  - https://doi.org/10.1016/j.jcs.2014.04.007
SN  - 0733-5210
SN  - 1095-9963
VL  - 60
IS  - 2
SP  - 440
EP  - 447
PB  - Elsevier
CY  - London
ER  - 
TY  - JOUR
A1  - Tu, Vo Anh
A1  - Kaga, Atsushi
A1  - Gericke, Karl-Heinz
A1  - Watanabe, Naoharu
A1  - Narumi, Tetsuo
A1  - Toda, Mitsuo
A1  - Brueckner, Bernhard
A1  - Baldermann, Susanne
A1  - Mase, Nobuyuki
T1  - Synthesis and characterization of quantum dot nanoparticles bound to the plant volatile precursor of Hydroxy-apo-10'-carotenal
JF  - The journal of organic chemistry
N2  - This study is focused on the synthesis and characterization of hydroxy-apo-10'-carotenal/quantum dot (QD) conjugates aiming at the in vivo visualization of beta-ionone, a carotenoid-derived volatile compound known for its important contribution to the flavor and aroma of many fruits, vegetables, and plants. The synthesis of nanoparticles bound to plant volatile precursors was achieved via coupling reaction of the QD to C-27-aldehyde which was prepared from alpha-ionone via 12 steps in 2.4% overall yield. The formation of the QD-conjugate was confirmed by measuring its fluorescence spectrum to observe the occurrence of fluorescence resonance energy transfer.
Y1  - 2014
U6  - https://doi.org/10.1021/jo500605c
SN  - 0022-3263
VL  - 79
IS  - 15
SP  - 6808
EP  - 6815
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Taleshi, Mojtaba S.
A1  - Seidler-Egdal, Rune K.
A1  - Jensen, Kenneth Bendix
A1  - Schwerdtle, Tanja
A1  - Francesconi, Kevin A.
T1  - Synthesis and Characterization of Arsenolipids: Naturally Occurring Arsenic Compounds in Fish and Algae
JF  - Organometallics
N2  - Arsenic-containing lipids (arsenolipids) are natural products present in fish and algae. Because these compounds occur in foods, there is considerable interest in their human toxicology. We report the synthesis and characterization of seven arsenic-containing lipids, including six natural products. The compounds comprise dimethylarsinyl groups attached to saturated long-chain hydrocarbons (three compounds), saturated long-chain fatty acids (two compounds), and monounsaturated long chain fatty acids (two compounds). The arsenic group was introduced through sodium dimethylarsenide or bis(dimethylarsenic) oxide. The latter route provided higher and more reproducible yields, and consequently, this pathway was followed to synthesize six of the seven compounds. Mass spectral properties are described to assist in the identification of these compounds in natural samples. The pure synthesized arsenolipids will be used for in vitro experiments with human cells to test their uptake, biotransformation, and possible toxic effects.
Y1  - 2014
U6  - https://doi.org/10.1021/om4011092
SN  - 0276-7333
SN  - 1520-6041
VL  - 33
IS  - 6
SP  - 1397
EP  - 1403
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Sic, Heiko
A1  - Kraus, Helene
A1  - Madl, Josef
A1  - Flittner, Karl-Andreas
A1  - von Muenchow, Audrey Lilly
A1  - Pieper, Kathrin
A1  - Rizzi, Marta
A1  - Kienzler, Anne-Kathrin
A1  - Ayata, Korcan
A1  - Rauer, Sebastian
A1  - Kleuser, Burkhard
A1  - Salzer, Ulrich
A1  - Burger, Meike
A1  - Zirlik, Katja
A1  - Lougaris, Vassilios
A1  - Plebani, Alessandro
A1  - Roemer, Winfried
A1  - Loeffler, Christoph
A1  - Scaramuzza, Samantha
A1  - Villa, Anna
A1  - Noguchi, Emiko
A1  - Grimbacher, Bodo
A1  - Eibel, Hermann
T1  - Sphingosine-1-phosphate receptors control B-cell migration through signaling components associated with primary immunodeficiencies, chronic lymphocytic leukemia, and multiple sclerosis
JF  - The journal of allergy and clinical immunology
N2  - Background: Five different G protein-coupled sphingosine-1-phosphate (S1P) receptors (S1P1-S1P5) regulate a variety of physiologic and pathophysiologic processes, including lymphocyte circulation, multiple sclerosis (MS), and cancer. Although B-lymphocyte circulation plays an important role in these processes and is essential for normal immune responses, little is known about S1P receptors in human B cells.
 Objective: To explore their function and signaling, we studied B-cell lines and primary B cells from control subjects, patients with leukemia, patients with S1P receptor inhibitor-treated MS, and patients with primary immunodeficiencies.
 Methods: S1P receptor expression was analyzed by using multicolor immunofluorescence microscopy and quantitative PCR. Transwell assays were used to study cell migration. S1P receptor internalization was visualized by means of time-lapse imaging with fluorescent S1P receptor fusion proteins expressed by using lentiviral gene transfer. B-lymphocyte subsets were characterized by means of flow cytometry and immunofluorescence microscopy.
 Results: Showing that different B-cell populations express different combinations of S1P receptors, we found that S1P1 promotes migration, whereas S1P4 modulates and S1P2 inhibits S1P1 signals. Expression of CD69 in activated B lymphocytes and B cells from patients with chronic lymphocytic leukemia inhibited S1P-induced migration. Studying B-cell lines, normal B lymphocytes, and B cells from patients with primary immunodeficiencies, we identified Bruton tyrosine kinase, beta-arrestin 2, LPS-responsive beige-like anchor protein, dedicator of cytokinesis 8, and Wiskott-Aldrich syndrome protein as critical signaling components downstream of S1P1.
 Conclusion: Thus S1P receptor signaling regulates human B-cell circulation and might be a factor contributing to the pathology of MS, chronic lymphocytic leukemia, and primary immunodeficiencies.
KW  - Sphingosine-1-phosphate
KW  - B cells
KW  - migration
KW  - autoimmunity
KW  - circulation
KW  - fingolimod
KW  - FTY720
KW  - primary immunodeficiencies
Y1  - 2014
U6  - https://doi.org/10.1016/j.jaci.2014.01.037
SN  - 0091-6749
SN  - 1097-6825
VL  - 134
IS  - 2
SP  - 420
EP  - +
PB  - Elsevier
CY  - New York
ER  - 
TY  - JOUR
A1  - Sharkovska, Yuliya
A1  - Reichetzeder, Christoph
A1  - Alter, Markus L.
A1  - Tsuprykov, Oleg
A1  - Bachmann, Sebastian
A1  - Secher, Thomas
A1  - Klein, Thomas
A1  - Hocher, Berthold
T1  - Blood pressure and glucose independent renoprotective effects of dipeptidyl peptidase-4 inhibition in a mouse model of type-2 diabetic nephropathy
JF  - Journal of hypertension
N2  - Background: Despite the beneficial effects of type 4 dipeptidyl peptidase (DPP-4) inhibitors on glucose levels, its effects on diabetic nephropathy remain unclear.
 Method: This study examined the long-term renoprotective effects of DPP-4 inhibitor linagliptin in db/db mice, a model of type 2 diabetes.
 Results were compared with the known beneficial effects of renin-angiotensin system blockade by enalapril. Ten-week-old male diabetic db/db mice were treated for 3 months with either vehicle (n = 10), 3 mg linagliptin/kg per day (n = 8), or 20 mg enalapril/kg per day (n = 10). Heterozygous db/m mice treated with vehicle served as healthy controls (n = 8). Results: Neither linagliptin nor enalapril had significant effects on the parameters of glucose metabolism or blood pressure in diabetic db/db mice. However, linagliptin treatment reduced albuminuria and attenuated kidney injury. In addition, expression of podocyte marker podocalyxin was normalized. We also analysed DPP-4 expression by immunofluorescence in human kidney biopsies and detected upregulation of DPP-4 in the glomeruli of patients with diabetic nephropathy, suggesting that our findings might be of relevance for human kidney disease as well.
 Conclusion: Treatment with DPP-4 inhibitor linagliptin delays the progression of diabetic nephropathy damage in a glucose-independent and blood-pressure-independent manner. The observed effects may be because of the attenuation of podocyte injury and inhibition of myofibroblast transformation.
KW  - diabetic nephropathy
KW  - DPP-4 inhibitors
KW  - linagliptin
Y1  - 2014
U6  - https://doi.org/10.1097/HJH.0000000000000328
SN  - 0263-6352
SN  - 1473-5598
VL  - 32
IS  - 11
SP  - 2211
EP  - 2223
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - CHAP
A1  - Scholze, Alexandra
A1  - Petersen, Lise
A1  - Hocher, Berthold
A1  - Rasmussen, Lars M.
A1  - Tepel, Martin
T1  - Role of fibroblast growth factor-23 and soluble alpha klotho in chronic  kidney disease
T2  - Nephrology, dialysis, transplantation
Y1  - 2014
SN  - 0931-0509
SN  - 1460-2385
VL  - 29
SP  - 120
EP  - 121
PB  - Oxford Univ. Press
CY  - Oxford
ER  -