Hakan Sarioglu's research while affiliated with Max-Planck-Forschungsstelle für Enzymologie der Proteinfaltung and other places

Publications (67)

Article
To study the influence of colloidal stability on protein corona formation, gold nanoparticles are synthesized with five distinct surface modifications: coating with citric acid, bis(p-sulfonatophenyl)phenylphosphine dihydrate dipotassium salt, thiol-terminated methoxy-polyethylene glycol, dodecylamine-grafted poly(isobutylene-alt-maleic anhydride),...
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Nitric oxide is an important signalling molecule which is involved in many different physiological processes in plants. Here we report about a NO-fixing mechanism in Arabidopsis, which allows the fixation of atmospheric NO into nitrogen metabolism. We fumigated Arabidopsis plants cultivated in soil or as hydroponic cultures during the whole growing...
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A combined transcriptome and proteome analysis of mouse radiation-induced AMLs using two primary AMLs, cell lines from these primaries, another cell line and its in vivo passage is reported. Compared to haematopoietic progenitor and stem cells (HPSC), over 5000 transcriptome alterations were identified, 2600 present in all materials. 55 and 3 alter...
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It has been suggested that a mechanistic understanding of the cellular responses to low dose and dose rate may be valuable in reducing some of the uncertainties involved in current risk estimates for cancer- and non-cancer-related radiation effects that are inherited in the linear no-threshold hypothesis. In this study, the effects of low-dose radi...
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Cucurbits developed the unique extrafascicular phloem (EFP) as a defensive structure against herbivorous animals. Mechanical leaf injury was previously shown to induce a systemic wound response in the EFP of pumpkin (Cucurbita maxima). Here, we demonstrate that the phloem antioxidant system and protein modifications by NO are strongly regulated dur...
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While it is widely accepted that ectopic lipid accumulation in the liver is associated with hepatic insulin resistance, the underlying molecular mechanisms have not been well characterized. Here we employed time resolved quantitative proteomic profiling of mice fed a high fat diet to determine which pathways were affected during the transition of t...
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Excess lipid intake has been implicated in the pathophysiology of hepatosteatosis and hepatic insulin resistance. Lipids constitute approximately 50% of the cell membrane mass, define membrane properties, and create microenvironments for membrane-proteins. In this study we aimed to resolve temporal alterations in membrane metabolite and protein sig...
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Epidemiological data from radiotherapy patients show the damaging effect of ionising radiation on heart and vasculature. The endothelium is the main target of radiation damage and contributes essentially to the development of cardiac injury. However, the molecular mechanisms behind the radiation-induced endothelial dysfunction are not fully underst...
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Despite the importance of superoxide dismutases (SODs) in the plant antioxidant defence system little is known about their regulation by post-translational modifications. Here, we investigated the in vitro effects of nitric oxide derivatives on the seven SOD isoforms of Arabidopsis thaliana. S-nitrosoglutathione, which causes S-nitrosylation of cys...
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Background: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these d...
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Systemic acquired resistance (SAR) is an inducible immune response that depends on ENHANCED DISEASE SUSCEPTIBILITY1 (EDS1). Here, we show that Arabidopsis thaliana EDS1 is required for both SAR signal generation in primary infected leaves and SAR signal perception in systemic uninfected tissues. In contrast to SAR signal generation, local resistanc...
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microRNAs (miRNAs) are non-coding RNAs that alter the stability and translation efficiency of messenger RNAs. Ionizing radiation (IR) induces rapid and selective changes in miRNA expression. Depletion of the miRNA processing enzymes Dicer or Ago2 reduces the capacity of cells to survive radiation exposure. Elucidation of critical radiation-regulate...
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When nanoparticles (NP) enter the body they come into contact with body fluids containing proteins which can adsorb to their surface. These proteins may influence the NP interactions with the biological vicinity, eventually determining their biological fate inside the body.Adsorption of the most abundantly binding proteins was studied after an in v...
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Radiation exposure of the thorax is associated with a markedly increased risk of cardiac morbidity and mortality with a latency period of decades. Although many studies have confirmed the damaging effect of ionizing radiation on the myocardium and cardiac endothelial structure and function, the molecular mechanism behind this damage is not yet eluc...
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Chronic low-dose ionizing radiation induces cardiovascular disease in human populations but the mechanism is largely unknown. We suggested that chronic radiation exposure may induce endothelial cell senescence that is associated with vascular damage in vivo. We investigated whether chronic radiation exposure is causing a change in the onset of sene...
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Background and purpose: Radiotherapy of thoracic and chest-wall tumours increases the long-term risk of radiation-induced heart disease. The aim of this study was to investigate the long-term effect of local heart irradiation on cardiac mitochondria. Methods: C57BL/6 and atherosclerosis-prone ApoE(-/-) mice received local heart irradiation with...
Article
Formin-like 1 (FMNL1) is a formin-related protein highly expressed in hematopoietic cells and overexpressed in leukemias as well as diverse transformed cell lines. It has been described to play a role in diverse functions of hematopoietic cells such as phagocytosis of macrophage as well as polarization and cytotoxicity of T cells. However, the spec...
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High doses of ionising radiation significantly increase the risk of cardiovascular disease (CVD), the vascular endothelium representing one of the main targets. Whether radiation doses lower than 500 mGy induce cardiovascular damage is controversial. The aim of this study was to investigate radiation-induced expression changes on protein and microR...
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The quality of human tissue specimens can have a significant impact on analytical data sets for biomarker research. The aim of this study was to characterise fluctuations of protein and phosphoprotein levels in human tissue samples during the pre-analytical phase. Eleven intestine and 17 liver specimens were surgically resected, aliquoted and eithe...
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In cucurbits phloem latex exudes from cut sieve tubes of the extrafascicular phloem (EFP) serving in defense against herbivores. We analyzed inducible defense mechanisms in the EFP of Cucurbita maxima after leaf damage. As an early systemic response, wounding elicited transient accumulation of jasmonates and a decrease in exudation probably due to...
Article
Protein expression analysis is one of the most powerful tools to further the understanding of biological systems. Progress in the field of mass spectrometry has shifted focus from gel-based approaches to the upcoming LC-selected reaction monitoring (SRM) technique which combines high technical accuracy with absolute quantification of proteins and t...
Data
TNIK identification by mass spectrometry. The significance threshold for Mascot search (MOWSE score p value 0.05) was 28 and corresponds to a protein score confidence interval (C.I.) of 95%. (DOC)
Data
The exogenous TNIK kinase domain requires endogenous TNIK to activate IKKβ in HEK293 cells. HEK293 cells were transfected in 6-well plates with TNIK siRNA or non-targeting siRNA. Subsequently, 2 µg of pRK5-HA-TNIK-KDwob or empty vector were co-transfected with 1 µg Flag-IKKβ and IKKβ kinase assays were performed. pRK5-HA-TNIK-KDwob expresses the wi...
Data
Effects of TNIK knockdown on EREB2-5 morphology. Microscopic images of the experiment shown in Figure 5B taken at day 3 after TNIK knockdown. Two representative images are shown each for Accell siTNIK and Accell siCTR treatment. The siCTR samples show typical LCL clusters containing mostly healthy and rounded cells. In contrast, the knockdown of TN...
Data
LMP1-CTAR2 induces an interaction between TNIK and TRAF2. HEK293 cells were transfected in 10 cm cell culture dishes with 0.5 µg each of HA-TNIK wildtype, pRK-TRAF2, or 3 µg each of the HA-LMP1 constructs as indicated. Cells were lysed and TNIK was precipitated using the anti-TNIK antibody. Lysates and immunoprecipitations were analyzed by immunobl...
Data
HA-LMP1-liTEV-CT induces signaling. HEK293 cells were transfected with expression vectors for HA-LMP1 and HA-LMP1-li-TEV-CT. HA-LMP1(AAA, Y384G) harboring mutated CTAR1 and CTAR2 domains served as null control. Co-transfected HA-JNK1 was immunoprecipitated and in vitro JNK1 assays were performed using GST-c-Jun as a substrate. Immunoprecipitated HA...
Data
TNIK peptides identified by mass spectrometry in the TEV eluate of HA-LMP1-liTEV-CT immunoprecipitated from LCL-TEV.5 cells. (DOC)
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The tumor necrosis factor-receptor-associated factor 2 (TRAF2)- and Nck-interacting kinase (TNIK) is a ubiquitously expressed member of the germinal center kinase family. The TNIK functions in hematopoietic cells and the role of TNIK-TRAF interaction remain largely unknown. By functional proteomics we identified TNIK as interaction partner of the l...
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The field of proteomics suffers from the immense complexity of even small proteomes and the enormous dynamic range of protein concentrations within a given sample. Most protein samples contain a few major proteins, which hamper in-depth proteomic analysis. In the human field, combinatorial hexapeptide ligand libraries (CPLL; such as ProteoMiner) ha...
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a b s t r a c t Exposure to allergens is pivotal in determining sensitization and allergic symptoms in individuals. Pollen grain counts in ambient air have traditionally been assessed to estimate airborne allergen exposure. However, the exact allergen content of ambient air is unknown. We therefore monitored atmospheric concentrations of birch poll...
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Epidemiological data show that ionising radiation increases the risk of cardiovascular disease. The endothelium is one of the main targets of radiation-induced damage. Rapid radiation-induced alterations in the biological processes were investigated after exposure to a clinically relevant radiation dose (2.5 Gy gamma radiation). The changes in prot...
Article
To characterize proteomic changes found in Barrett's adenocarcinoma and its premalignant stages, the proteomic profiles of histologically defined precursor and invasive carcinoma lesions were analyzed by MALDI imaging MS. For a primary proteomic screening, a discovery cohort of 38 fresh frozen Barrett's adenocarcinoma patient tissue samples was use...
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Backround Radiation therapy treatment of breast cancer, Hodgkin's disease or childhood cancers expose the heart to high local radiation doses, causing an increased risk of cardiovascular disease in the survivors decades after the treatment. The mechanisms that underlie the radiation damage remain poorly understood so far. Previous data show that im...
Data
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Verification of mitochondrial purity, quantification of protein standards by ICPL, gel pictures, functional respiratory measurements, aconitase activity and mitochondrial electron microscopic images. (PDF)
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Proteomics-based approaches allow us to investigate the biology of cancer beyond genomic initiatives. We used histology-based matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry to identify proteins that predict disease outcome in gastric cancer after surgical resection. A total of 181 intestinal-type primary resected gast...
Article
In papillary thyroid carcinoma (PTC), metastasis is a feature of an aggressive tumor phenotype. To identify protein biomarkers that distinguish patients with an aggressive tumor behavior, proteomic signatures in metastatic and non-metastatic tumors were investigated comparatively. In particular, matrix-assisted laser desorption/ionization (MALDI) i...
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Accidental nuclear scenarios lead to environmental contamination of unknown level. Immediate radiation-induced biological responses that trigger processes leading to adverse health effects decades later are not well understood. A comprehensive proteomic analysis provides a promising means to identify and quantify the initial damage after radiation...
Article
In recent years, nitric oxide (NO) has been recognized as a signalling molecule of plants, being involved in diverse processes like germination, root growth, stomatal closing, and responses to various stresses. A mechanism of how NO can regulate physiological processes is the modulation of cysteine residues of proteins (S-nitrosylation) by S-nitros...
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High doses of ionising radiation damage the heart by an as yet unknown mechanism. A concern for radiological protection is the recent epidemiological data indicating that doses as low as 100-500 mGy may induce cardiac damage. The aim of this study was to identify potential molecular targets and/or mechanisms involved in the pathogenesis of low-dose...
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Mutations in leucine-rich repeat kinase 2 (LRRK2) are the single most common cause of inherited Parkinson's disease. Little is known about its involvement in the pathogenesis of Parkinson's disease mainly because of the lack of knowledge about the physiological role of LRRK2. To determine the function of LRRK2, we studied the impact of short hairpi...
Article
Formalin-fixed paraffin-embedded (FFPE) tissue has recently gained interest as an alternative to fresh/frozen tissue for retrospective protein biomarker discovery. However, during the fixation process, proteins undergo degradation and cross-linking, making conventional protein analysis technologies problematic. In this study, we have compared sever...
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Mutations in leucine-rich repeat kinase 2 (LRRK2) that increase its kinase activity associate with familial forms of Parkinson disease (PD). As phosphorylation determines the functional state of most protein kinases, we systematically mapped LRRK2 phosphorylation sites by mass spectrometry. Our analysis revealed a high degree of constitutive phosph...
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As part of a comprehensive survey of the impact of the environmental pollutant and hepatocarcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the proteome of hepatic cells, we have performed a high resolution two-dimensional gel electrophoresis study on the rat hepatoma cell line 5L. 78 protein species corresponding to 73 different proteins wer...
Article
In an effort to contribute to a better understanding of the hepatic toxicity of the ubiquitous environmental pollutant and hepatocarcinogen 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a comprehensive quantitative proteome analysis was performed on 5L rat hepatoma cells exposed to 1 nM TCDD for 8 h. Changes in the abundances of individual protein sp...
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The ricinosome (synonym, precursor protease vesicle) is a novel organelle, found so far exclusively in plant cells. Electron microscopic studies suggest that it buds off from the endoplasmic reticulum in senescing tissues. Biochemical support for this unusual origin now comes from the composition of the purified organelle, which contains large amou...
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The human plasma protein patterns obtained by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) is a good model system for post-translational modifications because of the existence of several "ladders" of protein spots [Anderson, N. L., Anderson, N. G., Electrophoresis 1991, 12, 883-906], so-called "trains" of spots. Our investigation o...
Article
Mammalian thioredoxin reductase (TrxR) catalyzes reduction of thioredoxin and many other substrates, and is a central enzyme for cell proliferation and thiol redox control. The enzyme is a selenoprotein and can therefore, like all other mammalian selenoproteins, not be directly expressed in Escherichia coli, since selenocysteine-containing proteins...
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Introduction The human plasma protein pattern obtained by two-dimensional polyacrylamide gel electrophoresis (2DPAGE) consists of several "ladders" of spots, so called charged trains, often explained by posttranslational modifications, like glycosylation or phosphorylation (1). Another common post-translational modification observed to occur under...
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Nach der kompletten Sequenzierung des menschlichen Genoms im Rahmen des „Human Genome Project“ sind sich die Experten einig, dass die Forschung sich nun den Vorgängen der komplexen Regulationsnetzwerken auf der Proteinebene widmen muß. Die Proteomforschung bedient sich dabei der möglichst optimalen und quantitativen Auflösung von komplexen Proteing...

Citations

... Interaction time Abundant proteins dominate NP surface within an hour of interaction Johnston et al. (2017) High-affinity proteins start replacing the abundant proteins and protein exchange lowers within few hours Prakash and Deswal. (2020) Eventually, PC becomes stable due to lowest disassociation constant after several hours. ...
... The model has several advantages, including, (i) the very low background leukemia incidence (i.e. less than 1 in 1,000 mice), (ii) the reproducible rAML induction in 15-20% of mice 9 to 18 months following radiation exposure to a single acute 3 Gy whole-body X-irradiation, (the optimal rAML induction dose) (Bouffler et al. 1997), and (iii) the histopathological similarities with human myeloid leukemia. In particular, the increased white blood cell (WBC) count, hepato-/splenomegaly and myeloblastic infiltration of the bone marrow, liver and spleen (Major 1979) make it a relevant model for human AML ( Verbiest et al. 2015) and we confirmed that pathways of leukemogenesis in the mouse and human share substantial commonality ( Badie et al. 2016). Genetic background plays an important role in radiationinduced leukemogenesis as illustrated by the work of Patel et al. (2016) where it was shown that a single polymorphism (Q418P) of the DNA repair gene CTIP can predispose a specific mouse strain to radiation-induced leukemogenesis. ...