TY  - GEN
A1  - Scarpeci, Telma E.
A1  - Zanor, María I.
A1  - Carrillo, Néstor
A1  - Mueller-Roeber, Bernd
A1  - Valle, Estela M.
T1  - Generation of superoxide anion in chloroplasts of Arabidopsis thaliana during active photosynthesis
BT  - a focus on rapidly induced genes
T2  - Postprints der Universität Potsdam : Mathematisch Naturwissenschaftliche Reihe
N2  - The antioxidant defense system involves complex functional coordination of multiple components in different organelles within the plant cell. Here, we have studied the Arabidopsis thaliana early response to the generation of superoxide anion in chloroplasts during active photosynthesis. We exposed plants to methyl viologen (MV), a superoxide anion propagator in the light, and performed biochemical and expression profiling experiments using Affymetrix ATH1 GeneChip(R) microarrays under conditions in which photosynthesis and antioxidant enzymes were active. Data analysis identified superoxide-responsive genes that were compared with available microarray results. Examples include genes encoding proteins with unknown function, transcription factors and signal transduction components. A common GAAAAGTCAAAC motif containing the W-box consensus sequence of WRKY transcription factors, was found in the promoters of genes highly up-regulated by superoxide. Band shift assays showed that oxidative treatments enhanced the specific binding of leaf protein extracts to this motif. In addition, GUS reporter gene fused to WRKY30 promoter, which contains this binding motif, was induced by MV and H2O2. Overall, our study suggests that genes involved in signalling pathways and with unknown functions are rapidly activated by superoxide anion generated in photosynthetically active chloroplasts, as part of the early antioxidant response of Arabidopsis leaves.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 866 
KW  - antioxidant response
KW  - chloroplast
KW  - Hsp
KW  - oxidative stress
KW  - WRKY
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-434254
SN  - 1866-8372
IS  - 866
SP  - 361
EP  - 378
ER  - 
TY  - JOUR
A1  - Haase, Andrea
A1  - Arlinghaus, Heinrich F.
A1  - Tentschert, Jutta
A1  - Jungnickel, Harald
A1  - Graf, Philipp
A1  - Mantion, Alexandre
A1  - Draude, Felix
A1  - Galla, Sebastian
A1  - Plendl, Johanna
A1  - Goetz, Mario E.
A1  - Masic, Admir
A1  - Meier, Wolfgang P.
A1  - Thuenemann, Andreas F.
A1  - Taubert, Andreas
A1  - Luch, Andreas
T1  - Application of Laser Postionization Secondary Neutral Mass Spectrometry/Time-of-Flight Secondary Ion Mass Spectrometry in Nanotoxicology: Visualization of Nanosilver in Human Macrophages and Cellular Responses
JF  - ACS nano
N2  - Silver nanoparticles (SNP) are the subject of worldwide commercialization because of their antimicrobial effects. Yet only little data on their mode of action exist. Further, only few techniques allow for visualization and quantification of unlabeled nanoparticles inside cells. To study SNP of different sizes and coatings within human macrophages, we introduce a novel laser postionization secondary neutral mass spectrometry (Laser-SNMS) approach and prove this method superior to the widely applied confocal Raman and transmission electron microscopy. With time-of-flight secondary ion mass spectrometry (TOF-SIMS) we further demonstrate characteristic fingerprints in the lipid pattern of the cellular membrane indicative of oxidative stress and membrane fluidity changes. Increases of protein carbonyl and heme oxygenase-1 levels in treated cells confirm the presence of oxidative stress biochemically. Intriguingly, affected phagocytosis reveals as highly sensitive end point of SNP-mediated adversity In macrophages. The cellular responses monitored are. hierarchically linked, but follow individual kinetics and are partially reversible.
KW  - nanosilver
KW  - Laser-SNMS
KW  - TOF-SIMS
KW  - confocal Raman microscopy
KW  - oxidative stress
KW  - protein carbonyls
Y1  - 2011
U6  - https://doi.org/10.1021/nn200163w
SN  - 1936-0851
VL  - 5
IS  - 4
SP  - 3059
EP  - 3068
PB  - American Chemical Society
CY  - Washington
ER  - 
TY  - JOUR
A1  - Haase, Andrea
A1  - Rott, Stephanie
A1  - Mantion, Alexandre
A1  - Graf, Philipp
A1  - Plendl, Johanna
A1  - Thünemann, Andreas F.
A1  - Meier, Wolfgang P.
A1  - Taubert, Andreas
A1  - Luch, Andreas
A1  - Reiser, Georg
T1  - Effects of silver nanoparticles on primary mixed neural cell cultures: Uptake, oxidative stress and acute calcium responses
JF  - Toxicological sciences
N2  - In the body, nanoparticles can be systemically distributed and then may affect secondary target organs, such as the central nervous system (CNS). Putative adverse effects on the CNS are rarely investigated to date. Here, we used a mixed primary cell model consisting mainly of neurons and astrocytes and a minor proportion of oligodendrocytes to analyze the effects of well-characterized 20 and 40 nm silver nanoparticles (SNP). Similar gold nanoparticles served as control and proved inert for all endpoints tested. SNP induced a strong size-dependent cytotoxicity. Additionally, in the low concentration range (up to 10 mu g/ml of SNP), the further differentiated cultures were more sensitive to SNP treatment. For detailed studies, we used low/medium dose concentrations (up to 20 mu g/ml) and found strong oxidative stress responses. Reactive oxygen species (ROS) were detected along with the formation of protein carbonyls and the induction of heme oxygenase-1. We observed an acute calcium response, which clearly preceded oxidative stress responses. ROS formation was reduced by antioxidants, whereas the calcium response could not be alleviated by antioxidants. Finally, we looked into the responses of neurons and astrocytes separately. Astrocytes were much more vulnerable to SNP treatment compared with neurons. Consistently, SNP were mainly taken up by astrocytes and not by neurons. Immunofluorescence studies of mixed cell cultures indicated stronger effects on astrocyte morphology. Altogether, we can demonstrate strong effects of SNP associated with calcium dysregulation and ROS formation in primary neural cells, which were detectable already at moderate dosages.
KW  - silver nanoparticles
KW  - neurons
KW  - oxidative stress
KW  - protein carbonyls
KW  - calcium
Y1  - 2012
U6  - https://doi.org/10.1093/toxsci/kfs003
SN  - 1096-6080
VL  - 126
IS  - 2
SP  - 457
EP  - 468
PB  - Oxford Univ. Press
CY  - Oxford
ER  - 
TY  - JOUR
A1  - Chaykovska, Lyubov
A1  - Alter, Markus L.
A1  - von Websky, Karoline
A1  - Hohmann, Margarete
A1  - Tsuprykov, Oleg
A1  - Reichetzeder, Christoph
A1  - Kutil, Barbara
A1  - Kraft, Robin
A1  - Klein, Thomas
A1  - Hocher, Berthold
T1  - Effects of telmisartan and linagliptin when used in combination on blood pressure and oxidative stress in rats with 2-kidney-1-clip hypertension
JF  - Journal of hypertension
N2  - Objective:To investigate the effects of linagliptin alone and in combination with the angiotensin II receptor blocker (ARB), telmisartan on blood pressure (BP), kidney function, heart morphology and oxidative stress in rats with renovascular hypertension.Methods:Fifty-seven male Wistar rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2k1c) method]. Animals were randomly divided into four treatment groups (n=14-18 per group) receiving: telmisartan (10mg/kg per day in drinking water), linagliptin (89ppm in chow), combination (linagliptin 89ppm+telmisartan 10mg/kg per day) or placebo. An additional group of 12 rats underwent sham surgery. BP was measured one week after surgery. Hypertensive animals entered a 16-week dosing period. BP was measured 2, 4, 8, 12 and 16 weeks after the initiation of treatment. Blood and urine were tested for assessment of kidney function and oxidative stress 6, 10, 14 and 18 weeks after surgery. Blood and urine sampling and organ harvesting were finally performed.Results:Renal stenosis caused an increase in meanSD systolic BP as compared with the sham group (157.7 +/- 29.3 vs. 106.2 +/- 20.5mmHg, respectively; P<0.001). Telmisartan alone and in combination with linagliptin, normalized SBP (111.1 +/- 24.3mmHg and 100.4 +/- 13.9mmHg, respectively; P<0.001 vs. placebo). Telmisartan alone and in combination with linagliptin significantly prevented cardiac hypertrophy, measured by heart weight and myocyte diameter. Renal function measured by cystatin C was not affected by 2k1c surgery. Telmisartan significantly increased plasma concentration of cystatin C. 2k1c surgery initiated fibrosis in both kidneys. Telmisartan promoted further fibrotic changes in the clipped kidney, as measured by protein expression of Col1a1 and histology for interstitial fibrosis and glomerulosclerosis. In non-clipped kidneys, telmisartan demonstrated antifibrotic properties, reducing Col1a1 protein expression. Plasma levels of oxidized low-density lipoprotein were higher in the placebo-treated 2k1c rats as compared to sham-operated animals. The increase was abolished by linagliptin alone (P=0.03 vs. placebo) and in combination with telmisartan (P=0.02 vs. placebo). Combination therapy also significantly reduced plasma concentration of carbonyl proteins (P=0.04 vs. placebo).Conclusion:Inhibition of type 4 dipeptidyl peptidase with linagliptin did not counter BP-lowering effects of ARB in 2k1c rats. Linagliptin reduced lipid and protein oxidation in 2k1c rats, and this effect was BP-independent.
KW  - 2k1c renovascular hypertension
KW  - blood pressure
KW  - DPP4 inhibition
KW  - linagliptin
KW  - oxidative stress
Y1  - 2013
U6  - https://doi.org/10.1097/HJH.0b013e3283649b4d
SN  - 0263-6352
SN  - 1473-5598
VL  - 31
IS  - 11
SP  - 2290
EP  - 2299
PB  - Lippincott Williams & Wilkins
CY  - Philadelphia
ER  - 
TY  - JOUR
A1  - Tentschert, J.
A1  - Draude, F.
A1  - Jungnickel, H.
A1  - Haase, A.
A1  - Mantion, Alexandre
A1  - Galla, S.
A1  - Thuenemann, Andreas F.
A1  - Taubert, Andreas
A1  - Luch, A.
A1  - Arlinghaus, H. F.
T1  - TOF-SIMS analysis of cell membrane changes in functional impaired human macrophages upon nanosilver treatment
JF  - Surface and interface analysis : an international journal devoted to the development and application of techniques for the analysis surfaces, interfaces and thin films
N2  - Silver nanoparticles (SNP) are among the most commercialized nanoparticles. Here, we show that peptide-coated SNP cause functional impairment of human macrophages. A dose-dependent inhibition of phagocytosis is observed after nanoparticle treatment, and pretreatment of cells with N-acetyl cysteine (NAC) can counteract the phagocytosis disturbances caused by SNP.
 Using the surface-sensitive mode of time-of-flight secondary ion mass spectrometry, in combination with multivariate statistical methods, we studied the composition of cell membranes in human macrophages upon exposure to SNP with and without NAC preconditioning. This method revealed characteristic changes in the lipid pattern of the cellular membrane outer leaflet in those cells challenged by SNP. Statistical analyses resulted in 19 characteristic ions, which can be used to distinguish between NAC pretreated and untreated macrophages. The present study discusses the assignments of surface cell membrane phospholipids for the identified ions and the resulting changes in the phospholipid pattern of treated cells. We conclude that the adverse effects in human macrophages caused by SNP can be partially reversed through NAC administration. Some alterations, however, remained.
KW  - silver nanoparticles
KW  - lipidomics
KW  - N-acetyl cysteine
KW  - phagocytosis
KW  - oxidative stress
Y1  - 2013
U6  - https://doi.org/10.1002/sia.5155
SN  - 0142-2421
VL  - 45
IS  - 1
SP  - 483
EP  - 485
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - GEN
A1  - Hoffmann, Linda Sarah
A1  - Kretschmer, Axel
A1  - Lawrenz, Bettina
A1  - Hocher, Berthold
A1  - Stasch, Johannes-Peter
T1  - Chronic activation of heme free Guanylate Cyclase leads to renal protection in Dahl salt-sensitive rats
T2  - Postprints der Universität Potsdam : Mathematisch naturwissenschaftliche Reihe
N2  - The nitric oxide (NO)/soluble guanylate cyclase (sGC)/cyclic guanosine monophasphate (cGMP)-signalling pathway is impaired under oxidative stress conditions due to oxidation and subsequent loss of the prosthetic sGC heme group as observed in particular in chronic renal failure. Thus, the pool of heme free sGC is increased under pathological conditions. sGC activators such as cinaciguat selectively activate the heme free form of sGC and target the disease associated enzyme. In this study, a therapeutic effect of long-term activation of heme free sGC by the sGC activator cinaciguat was investigated in an experimental model of salt-sensitive hypertension, a condition that is associated with increased oxidative stress, heme loss from sGC and development of chronic renal failure. For that purpose Dahl/ss rats, which develop severe hypertension upon high salt intake, were fed a high salt diet (8% NaCl) containing either placebo or cinaciguat for 21 weeks. Cinaciguat markedly improved survival and ameliorated the salt-induced increase in blood pressure upon treatment with cinaciguat compared to placebo. Renal function was significantly improved in the cinaciguat group compared to the placebo group as indicated by a significantly improved glomerular filtration rate and reduced urinary protein excretion. This was due to anti-fibrotic and antiinflammatory effects of the cinaciguat treatment. Taken together, this is the first study showing that long-term activation of heme free sGC leads to renal protection in an experimental model of hypertension and chronic kidney disease. These results underline the promising potential of cinaciguat to treat renal diseases by targeting the disease associated heme free form of sGC.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 489 
KW  - signal-transduction system
KW  - nitric-oxide
KW  - oxidative stress
KW  - independent activation
KW  - endothelial dysfunction
KW  - pulmonary-hypertension
KW  - cardiovascular-disease
KW  - therapeutic target
KW  - heart-failure
KW  - cyclic-GMP
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-408088
SN  - 1866-8372
IS  - 489
ER  - 
TY  - JOUR
A1  - Benina, Maria
A1  - Ribeiro, Dimas Mendes
A1  - Gechev, Tsanko S.
A1  - Müller-Röber, Bernd
A1  - Schippers, Jos H. M.
T1  - A cell type-specific view on the translation of mRNAs from ROS-responsive genes upon paraquat treatment of Arabidopsis thaliana leaves
JF  - Plant, cell & environment : cell physiology, whole-plant physiology, community physiology
N2  - Oxidative stress causes dramatic changes in the expression levels of many genes. The formation of a functional protein through successful mRNA translation is central to a coordinated cellular response. To what extent the response towards reactive oxygen species (ROS) is regulated at the translational level is poorly understood. Here we analysed leaf- and tissue-specific translatomes using a set of transgenic Arabidopsis thaliana lines expressing a FLAG-tagged ribosomal protein to immunopurify polysome-bound mRNAs before and after oxidative stress. We determined transcript levels of 171 ROS-responsive genes upon paraquat treatment, which causes formation of superoxide radicals, at the whole-organ level. Furthermore, the translation of mRNAs was determined for five cell types: mesophyll, bundle sheath, phloem companion, epidermal and guard cells. Mesophyll and bundle sheath cells showed the strongest response to paraquat treatment. Interestingly, several ROS-responsive transcription factors displayed cell type-specific translation patterns, while others were translated in all cell types. In part, cell type-specific translation could be explained by the length of the 5-untranslated region (5-UTR) and the presence of upstream open reading frames (uORFs). Our analysis reveals insights into the translational regulation of ROS-responsive genes, which is important to understanding cell-specific responses and functions during oxidative stress.
 The study illustrates the response of different Arabidopsis thaliana leaf cells and tissues to oxidative stress at the translational level, an aspect of reactive oxygen species (ROS) biology that has been little studied in the past. Our data reveal insights into how translational regulation of ROS-responsive genes is fine-tuned at the cellular level, a phenomenon contributing to the integrated physiological response of leaves to stresses involving changes in ROS levels.
KW  - Arabidopsis
KW  - gene regulation
KW  - oxidative stress
KW  - tissue-specific
KW  - translation
Y1  - 2015
U6  - https://doi.org/10.1111/pce.12355
SN  - 0140-7791
SN  - 1365-3040
VL  - 38
IS  - 2
SP  - 349
EP  - 363
PB  - Wiley-Blackwell
CY  - Hoboken
ER  - 
TY  - JOUR
A1  - Castro, José Pedro
A1  - Grune, Tilman
A1  - Speckmann, Bodo
T1  - The two faces of reactive oxygen species (ROS) in adipocyte function and dysfunction
JF  - Biological chemistry
N2  - White adipose tissue (WAT) is actively involved in the regulation of whole-body energy homeostasis via storage/ release of lipids and adipokine secretion. Current research links WAT dysfunction to the development of metabolic syndrome (MetS) and type 2 diabetes (T2D). The expansion of WAT during oversupply of nutrients prevents ectopic fat accumulation and requires proper preadipocyte-to-adipocyte differentiation. An assumed link between excess levels of reactive oxygen species (ROS), WAT dysfunction and T2D has been discussed controversially. While oxidative stress conditions have conclusively been detected in WAT of T2D patients and related animal models, clinical trials with antioxidants failed to prevent T2D or to improve glucose homeostasis. Furthermore, animal studies yielded inconsistent results regarding the role of oxidative stress in the development of diabetes. Here, we discuss the contribution of ROS to the (patho) physiology of adipocyte function and differentiation, with particular emphasis on sources and nutritional modulators of adipocyte ROS and their functions in signaling mechanisms controlling adipogenesis and functions of mature fat cells. We propose a concept of ROS balance that is required for normal functioning of WAT. We explain how both excessive and diminished levels of ROS, e. g. resulting from over supplementation with antioxidants, contribute to WAT dysfunction and subsequently insulin resistance.
KW  - adipogenesis
KW  - adipose tissue dysregulation
KW  - antioxidants
KW  - metabolic disorders
KW  - oxidative stress
Y1  - 2016
U6  - https://doi.org/10.1515/hsz-2015-0305
SN  - 1431-6730
SN  - 1437-4315
VL  - 397
SP  - 709
EP  - 724
PB  - De Gruyter
CY  - Berlin
ER  - 
TY  - JOUR
A1  - Endesfelder, Stefanie
A1  - Weichelt, Ulrike
A1  - Strauß, Evelyn
A1  - Schlör, Anja
A1  - Sifringer, Marco
A1  - Scheuer, Till
A1  - Bührer, Christoph
A1  - Schmitz, Thomas
T1  - Neuroprotection by caffeine in hyperoxia-induced neonatal brain injury
JF  - International journal of molecular sciences
N2  - Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term “oxygen radical disease of prematurity”. Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28–32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NFκB), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.
KW  - anti-oxidative response
KW  - caffeine
KW  - hyperoxia
KW  - oxidative stress
KW  - preterm infants
KW  - developing brain
Y1  - 2017
U6  - https://doi.org/10.3390/ijms18010187
SN  - 1422-0067
SN  - 1661-6596
VL  - 18
PB  - Molecular Diversity Preservation International
CY  - Basel
ER  - 
TY  - GEN
A1  - Endesfelder, Stefanie
A1  - Weichelt, Ulrike
A1  - Strauß, Evelyn
A1  - Schlör, Anja
A1  - Sifringer, Marco
A1  - Scheuer, Till
A1  - Bührer, Christoph
A1  - Schmitz, Thomas
T1  - Neuroprotection by caffeine in hyperoxia-induced neonatal brain injury
T2  - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe
N2  - Sequelae of prematurity triggered by oxidative stress and free radical-mediated tissue damage have coined the term "oxygen radical disease of prematurity". Caffeine, a potent free radical scavenger and adenosine receptor antagonist, reduces rates of brain damage in preterm infants. In the present study, we investigated the effects of caffeine on oxidative stress markers, anti-oxidative response, inflammation, redox-sensitive transcription factors, apoptosis, and extracellular matrix following the induction of hyperoxia in neonatal rats. The brain of a rat pups at postnatal Day 6 (P6) corresponds to that of a human fetal brain at 28-32 weeks gestation and the neonatal rat is an ideal model in which to investigate effects of oxidative stress and neuroprotection of caffeine on the developing brain. Six-day-old Wistar rats were pre-treated with caffeine and exposed to 80% oxygen for 24 and 48 h. Caffeine reduced oxidative stress marker (heme oxygenase-1, lipid peroxidation, hydrogen peroxide, and glutamate-cysteine ligase catalytic subunit (GCLC)), promoted anti-oxidative response (superoxide dismutase, peroxiredoxin 1, and sulfiredoxin 1), down-regulated pro-inflammatory cytokines, modulated redox-sensitive transcription factor expression (Nrf2/Keap1, and NF kappa B), reduced pro-apoptotic effectors (poly (ADP-ribose) polymerase-1 (PARP-1), apoptosis inducing factor (AIF), and caspase-3), and diminished extracellular matrix degeneration (matrix metalloproteinases (MMP) 2, and inhibitor of metalloproteinase (TIMP) 1/2). Our study affirms that caffeine is a pleiotropic neuroprotective drug in the developing brain due to its anti-oxidant, anti-inflammatory, and anti-apoptotic properties.
T3  - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 1097 
KW  - anti-oxidative response
KW  - caffeine
KW  - hyperoxia
KW  - oxidative stress
KW  - preterm infants
KW  - developing brain
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-475040
SN  - 1866-8372
IS  - 1097
ER  -