Maria Zellner

Medical University of Vienna | MedUni Vienna · Institute of Vascular Biology and Thrombosis Research

Proteomics is an indispensable analytical technique to study the dynamic functioning of biological systems via different proteins and their proteoforms. In recent years, bottom-up shotgun has become more popular than gel-based top-down proteomics. The current study examined the qualitative and quantitative performance of these two fundamentally dif...

Background: The fatal consequences of an infection with severe acute respiratory syndrome coronavirus 2 are not only caused by severe pneumonia, but also by thrombosis. Platelets are important regulators of thrombosis, but their involvement in the pathogenesis of COVID-19 is largely unknown. The aim of this study was to determine their functional a...

In order to comprehensively expose cancer-related biochemical changes, we compared the platelet proteome of two types of cancer with a high risk of thrombosis (22 patients with brain cancer, 19 with lung cancer) to 41 matched healthy controls using unbiased two-dimensional differential in-gel electrophoresis. The examined platelet proteome was unch...

Background The risk of venous thromboembolism in cancer is nine times higher than in the general population and the second leading cause of death in these patients. Platelets play a key role in tumour growth, metastasis, and cancer-associated thrombosis. Despite this widely observed functional role of platelets in the prothrombotic state of certain...

Patients with antiphospholipid syndrome (APS) are at high risk of developing venous and arterial thromboembolism (TE). The role of platelets in the pathogenesis of these prothrombotic conditions is not yet fully understood. The aim of this study was to gain mechanistic insights into the role of platelets in APS by comparing the platelet proteome be...

There is a need to assess platelet activation in patients with thrombotic disorders. P-selectin and activated integrin αIIbβ3 are usually quantified by flow cytometry to measure platelet activation. Monitoring changes in vasodilator-stimulated phosphoprotein (VASP) phosphorylation is an established method to determine the platelet-reactivity status...

Introduction Blood platelets are increasingly recognized as modulators of leukocyte effector functions in various pathologies including acute lung injury (ALI). ALI is a life-threatening disease, caused by damage to the alveolar epi- and endothelium. Excessive accumulation of leukocytes leads to severe lung inflammation, resulting in impaired lung...

The proteome is the entire set of proteins of a biological sample, and proteomics is the large-scale qualitative (protein composition) and quantitative analysis of the proteome. A collection of dedicated biochemical methods is combined with protein databases to identify the proteins and to allocate them to biological pathways. The work process invo...

Background Apolipoprotein E (APOE) is a key player in lipid transport and metabolism and exists in three common isoforms: APOE2, APOE3 and APOE4. The presence of the Methods Biochip array technology (BAT) was successfully applied to identify directly the APOE4 status from plasma within 3 h, through simultaneous immunoassay-based detection of both...

Significance: Platelet tropomyosin-1 constitutes a gender-related and stage-dependent protein in cognitive impairment. Whereas platelet monoamine oxidase-B, frequently described to be increased in platelets and brains of AD patients, shows a gender-independent but stage-related increase since it is unaltered in MCI subjects. A blood biomarker test...

Approximately 30 million people currently suffer from late-onset Alzheimer's disease (LOAD) worldwide. Twin studies demonstrated that 60 to 80% of LOAD is genetically determined, 20% of which remaining unassigned. This case-control study included 118 cognitively healthy controls, 52 patients with mild cognitive impairment (MCI; the pre-stage of LOA...

We previously showed that, when peripheral blood mononuclear cells (PBMCs) were stressed with ionizing radiation, they released paracrine factors that showed regenerative capacity in vitro and in vivo. This study aimed to characterize the secretome of PBMCs and to investigate its biologically active components in vitro and vivo. Bioinformatics anal...

Serine protease inhibitors have therapeutic potential in a variety of pathogenic processes, ranging from thrombosis and altered immune response to liver cirrhosis. To investigate the physiological effects of protein C inhibitor (PCI, serpinA5), its gene was inactivated in a mouse model, resulting in male infertility. In the present report, 2D-DIGE...

Alzheimer’s disease (AD), a multifactorial neurodegenerative condition caused by genetic and environmental factors, is diagnosed using neuropsychological tests and brain imaging; molecular diagnostics are not routinely applied. Studies have identified AD-specific cerebrospinal fluid (CSF) biomarkers but sample collection requires invasive lumbar pu...

Background and purposeDespite new therapeutic approaches metastatic melanomas have still a poor prognosis. Statins reduce LDL-cholesterol and exert anti-inflammatory and anti-proliferative actions. We have recently shown that, simvastatin triggers an apoptotic burst in human metastatic melanoma cells by the synthesis of an autocrine factor.Experime...

Peripheral biomarkers play an indispensable role in quick and reliable diagnoses of any kind of disease. With the population ageing, the number of people suffering from age-related diseases is expected to rise dramatically over the coming decades. In particular, all types of cognitive deficits, such as Alzheimer's disease (AD), will increase. AD is...

Unlabelled: Accurate biomarker quantification requires carefully chosen normalisation procedures. When single proteins are used as loading controls (LCs), it is crucial that their expressional stability must be known. Platelets are an important biomarker source, especially for neurological diseases. We performed a systematical analysis of the plat...

High biological variation in protein expression represents a major challenge in clinical proteomics. In a study based on 2D-DIGE, we found that the standardised abundance of only a few proteins varied by more than 50%. While some of the highest variable proteins in platelets of 52 healthy elderly were of plasmatic origin, such as albumin or haptogl...

Quantitative proteomic comparisons require a sufficient number of samples to reach an acceptable level of significance. But 2D gel electrophoresis commonly results in incomplete data sets due to spots with missing values reducing thereby the number of parallel measurements for individual proteins. Here we investigated how many missing values per sp...

Monoamine oxidase-B (Mao-B) catalysing the breakdown of the neurotransmitter dopamine, is known to be involved in the pathophysiology of Parkinson's (PD) and Alzheimer's disease (AD). Increased brain Mao-B activity is associated with AD. This alteration can also be seen in platelets, albeit the cause has hitherto remained elusive. To gain a deeper...

Platelets are maintained in an inactive state in the peripheral circulation and react rapidly in response to vascular injury. Removing platelets from their physiological environment can also result in platelet activation from a number of stimuli, including agonists generated or released during blood collection, mechanical forces exerted on platelet...

Recommendations to use other criteria than N-balance for defining protein requirements have been proposed. However, little evidence to support other measures such as physiological functions is available. To investigate the effects of a usual (UP) versus a high protein (HP) diet on muscle function, cognitive function, quality of life and biochemical...

Studies investigating the impact of high meat intake on cognition have yielded contradictory results as some show improved cognitive performance, whereas others report an increase of risk factors for dementia. However, few studies were designed to directly assess the effect of a high protein (HP) diet on both cognitive performance and corresponding...

OxLDL represents a central player in atherogenesis and has been shown to activate human blood platelets. In light of the pivotal role of CD40L in inflammation, it was the aim of this work to clarify if platelet-activating effects of oxidized LDL result in surface exposure and liberation of CD40L and to explore the role of platelet scavenger recepto...

Oxidative stress and systemic inflammation negatively affect several protective functions of high density lipoproteins (HDL) and oxidative modification of HDL by the inflammation-derived oxidant hypochlorite converts HDL into a potent platelet agonist. Therefore it was the aim of this work to clarify if these platelet-activating effects result from...

The only treatment of end-stage renal disease patients undergoing chronic dialysis is kidney transplantation. However, about half of graft recipients encounter organ loss within ten years after renal transplantation. There is emerging evidence that the presence of alloreactive antibodies against non-HLA antigens in the serum of the recipient prior...

Proteomic analysis enables us to identify dementia-related protein profiles of both genetic and environmental origins. In this review, current proteomics technologies are described including many examples of clinical proteomics studies. Many of these studies present only results of the discovery phase. Progression to the validation phase was achiev...

Despite the increasing use of granulocyte colony-stimulating factor (G-CSF) for the mobilization of stem cells and neutrophils, its pharmacodynamic actions are not fully understood. Because of the roles of G-CSF and gelatinase B in leucokinetics, we set out to characterize the interaction of G-CSF with its receptor in humans and its effects on gela...

Since most high throughput techniques used in biomarker discovery are very time and cost intensive, highly specific and quantitative analytical alternative application methods are needed for the routine analysis. Conventional Western blotting allows detection of specific proteins to the level of single isotypes while its quantitative accuracy is ra...

Knowledge about the extent of total variation experienced between samples from different individuals is of great importance for the design of not only proteomics but every clinical study. This variation defines the smallest statistically significant detectable signal difference when comparing two groups of individuals. We isolated platelets from 20...

In critically ill patients, clinicians observe a reverse correlation of survival and a decreased plasma concentration of the most abundant free amino acid, glutamine (Gln). However, in this context, the role of Gln remains largely elusive. Gln is used as an energy substrate by monocytes. Gln deprivation of these cells results in an increased suscep...

For the preparation of proteins for proteome analysis, precipitation is frequently used to concentrate proteins and to remove interfering compounds. Various methods for protein precipitation are applied, which rely on different chemical principles. This study compares the changes in the protein composition of human blood platelet extracts after pre...

This study investigates the effect of fever-range hyperthermia on Gln-starving monocytes and the role of the 70-kDa heat shock protein Hsp70. Fever is a protective acute-phase response to infection. However, in critically ill patients, the harmful effects of fever seem to be predominant. Critical illness is frequently associated with reduced plasma...

Stroke and stroke-like episodes are frequent complications in mitochondriopathy, particularly in MELAS syndrome (mitochondrial myopathy, encephalopathy, lactic acidosis and stroke like episodes) which is a disorder of the mitochondrial oxidative metabolism in diverse cell types. To clarify a possible pathological aspect of stroke in these patients,...

Peripheral blood monocytes utilize free glutamine (Gln) in addition to glucose as an important energy substrate. Although this demand increases upon activation, monocytes are commonly confronted with decreased plasma Gln during critical illness and thus suffer from Gln-starvation. Here we investigate the influence of Gln-starvation on protein stabi...

BACKGROUND: Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donor's health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated. STUDY DESIGN AND METHODS: Part 1: Sixteen healthy men were randomly assigned to...

The thermal effect of fever, an evolutionarily conserved acute-phase response, has been associated with better survival and a shorter duration of disease in cases of infection. The molecular consequence of this beneficial fever response is poorly understood. To determine the influence of hyperthermia on human monocytes, which are important for the...

During sepsis and major trauma the blood glutamine (Gln) level is reduced. The administration of Gln can improve the outcome of these patients. However, the mechanism of this beneficial effect of Gln is poorly understood. In the course of critical illness leucocytes are confronted with cytotoxic inflammatory mediators. To protect themselves against...

Fever has been associated with shortened duration and improved survival in infectious disease. The mechanism of this beneficial response is still poorly understood. The heat-inducible 70-kDa heat shock protein (Hsp70) has been associated with protection of leukocytes against the cytotoxicity of inflammatory mediators and with improved survival of s...

Despite the increasing use of granulocyte colony-stimulating factor (G-CSF) for the mobilization of stem cells and neutrophils, its pharmacodynamic actions are not fully understood. Because of the roles of G-CSF and gelatinase B in leucokinetics, we set out to characterize the interaction of G-CSF with its receptor in humans and its effects on gela...

Hsp70 is induced by hypoxia in most mammalian cell types and contributes to their ability to survive hypoxic episodes. However, little is known about Hsp70 expression in the hypoxia-tolerant endothelial cells (ECs). We investigated the effect of hypoxia on Hsp70 in human microvascular endothelial HMEC-1 cells. Reduction of pO(2) to 2.5% of normal f...

Nutrients play a pivotal role in the maintenance of energy and nitrogen balance. However, recent investigations revealed that nutrients can act by modulating the immune and vascular system and even influence signal transduction towards cell proliferation or cell death (apoptosis). Hence, we are entering a new area in clinical nutrition where indivi...

Although many donors undergo repeated plateletpheresis, data on the consequences of plateletpheresis for the donor's health remain scarce. Thus, the effect of plateletpheresis on the activation of coagulation, fibrinolysis, and neutrophils was investigated. Part 1: Sixteen healthy men were randomly assigned to undergo plateletpheresis on a cell sep...

Heat shock response provides cells with higher tolerance against a variety of insults such as heavy metals, reperfusion injury, and endotoxin. In addition, heat treatment is known to affect ion transport mechanisms associated with vital cellular processes, including cell volume regulation. However, there has been no reports to date of a heat shock...