A5078859740- Venomous Animal Envenomation and Studies
- Ion channel regulation and function
- Cellular transport and secretion
- Protein Kinase Regulation and GTPase Signaling
- Nicotinic Acetylcholine Receptors Study
- Marine Invertebrate Physiology and Ecology
- Blood Coagulation and Thrombosis Mechanisms
- Ubiquitin and proteasome pathways
- Marine Sponges and Natural Products
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Nanoparticle-Based Drug Delivery
- Mitochondrial Function and Pathology
- 14-3-3 protein interactions
- Monoclonal and Polyclonal Antibodies Research
- RNA Interference and Gene Delivery
- Peptidase Inhibition and Analysis
- Erythrocyte Function and Pathophysiology
- Antimicrobial agents and applications
- Extracellular vesicles in disease
- Nanopore and Nanochannel Transport Studies
- Microbial Natural Products and Biosynthesis
- Coenzyme Q10 studies and effects
- Plasma Applications and Diagnostics
- Allergic Rhinitis and Sensitization
- Glioma Diagnosis and Treatment
Jožef Stefan Institute
2013-2025
Jožef Stefan International Postgraduate School
2016-2022
University of Ljubljana
2020
Despite many advances in gene therapy, the delivery of small interfering RNAs is still challenging. Erythrocytes are most abundant cells human body, and their membrane possesses unique features. From them, erythrocytes vesicles can be generated, employable as nano drug system with prolonged blood residence high biocompatibility. Human erythrocyte ghosts were extruded presence siRNA, objects termed EMVs (erythrocyte vesicles). An ultracentrifugation-based method was applied to select only...
Glioblastoma is a particularly common and very aggressive primary brain tumour. One of the main causes therapy failure presence glioblastoma stem cells that are resistant to chemotherapy radiotherapy, have potential form new tumours. This study focuses on validation eight novel antigens, TRIM28, nucleolin, vimentin, nucleosome assembly protein 1-like 1 (NAP1L1), mitochondrial translation elongation factor (EF-TU) (TUFM), dihydropyrimidinase-related 2 (DPYSL2), collapsin response mediator...
One of the high affinity binding proteins for ammodytoxin C, a snake venom presynaptically neurotoxic phospholipase A<sub>2</sub>, has been purified from porcine cerebral cortex and characterized. After extraction membranes, toxin-binding protein was isolated in homogenous form using wheat germ lectin-Sepharose, Q-Sepharose, ammodytoxin-CH-Sepharose chromatography. The specific <sup>125</sup>I-ammodytoxin C to acceptor inhibited different extents by some phospholipases ammodytoxins, bee...
Disulfide pairings and active site residues are highly conserved in secretory phospholipases A(2) (PLA(2)s). However, PLA(2)s of marine invertebrates display some distinctive structural features. In this study, we report the isolation characterization a PLA(2) from northern Pacific sea anemone, Urticina crassicornis (UcPLA(2)), containing C27N substitution truncated C-terminal sequence. This novel cnidarian shares about 60% identity almost 70% homology with two putative identified starlet...
Abstract The β-neurotoxic secreted phospholipases A 2 (sPLA s) block neuro-muscular transmission by poisoning nerve terminals. Damage inflicted such sPLA s (β-ntx) on neuronal mitochondria is characteristic, very similar to that induced structurally homologous endogenous group IIA when its activity elevated, as, for example, in the early phase of Alzheimer’s disease. Using ammodytoxin (Atx), β-ntx from venom nose-horned viper ( Vipera a . ammodytes ), receptor R25 has been detected...
Background/Objectives: Glioblastomas are the most common brain malignancies. Despite implementation of multimodal therapy, patient life expectancy after diagnosis is barely 12 to 18 months. highly heterogeneous at genetic and epigenetic level comprise multiple different cell subpopulations. Therefore, small molecules such as nanobodies, able target membrane proteins specific glioblastoma cells or types within tumor being investigated novel tools treat glioblastomas. Methods: Here, we...
Astrocytes, the most heterogeneous glial cells in central nervous system, contribute to brain homeostasis, by regulating a myriad of functions, including clearance extracellular debris. When are damaged, cytoplasmic proteins may exit into space. One such protein is S100B, which exert toxic effects on neighboring unless it removed from space, but mechanisms this poorly understood. By using time-lapse confocal microscopy and fluorescently labeled S100B (S100B-Alexa488 ) fluorescent dextran...
Glioblastoma multiforme (GBM) is the most common and lethal form of brain tumor. The prognosis for patients remains poor, despite combination new preoperative intraoperative neuroimaging, radical surgery, recent advances in radiotherapy chemotherapy. To improve GBM therapy patient outcome, sustained drug delivery to glioma cells needed, while minimizing toxicity adjacent neurons glia cells. This might be achieved through an anti-proteomic approach based on nanobodies, single-domain...
Ammodytoxin is a presynaptically neurotoxic (β‐neurotoxic) snake venom secretory phospholipase A 2 (sPLA ). We detected 25 kDa protein which binds the toxin with very high affinity (R25) in porcine cerebral cortex [Vučemilo et al., Biochem. Biophys. Res. Commun. 251 (1998) 209–212]. Here we show that R25 an integral membrane intracellular localisation. It first sPLA receptor known to date localises membranes. Centrifugation on sucrose gradients was used fractionate cortex. The subcellular...
Abstract Components of the intrinsic blood coagulation pathway, among them factor VIIIa (FVIIIa), have been recognized as suitable therapeutic targets to treat venous thromboembolism, pathological process behind two very serious cardiovascular diseases, deep vein thrombosis and pulmonary embolism. Here, we describe a unique glycoprotein from nose-horned viper (Vipera ammodytes [Vaa]) venom, Vaa serine proteinase homolog 1 (VaaSPH-1), structurally protease but without an enzymatic activity...
β-Neurotoxins are secreted phospholipase A2 molecules that inhibit transmission in neuromuscular synapses by poisoning the motor neurons. These toxins specifically and rapidly internalise into nerve endings of Ammodytoxin (Atx) is a prototype β-neurotoxin from venom nose-horned viper (Vipera ammodytes ammodytes). Here, we studied relevance enzymatic activity Atx cell internalisation subsequent intracellular movement using electron microscopy (TEM). We prepared recombinant, enzymatically...
The molecular mechanism of the presynaptic neurotoxicity snake venom phospholipases A 2 (PLA s) is not yet fully elucidated. Recently, new high‐affinity binding proteins for PLA toxins have been discovered, including important intracellular Ca 2+ sensor, calmodulin (CaM). In present study, mode interaction group IIA s with ‐bound form CaM was investigated by mutational analysis ammodytoxin (AtxA) from long‐nosed viper ( Vipera ammodytes ). Several residues in C‐terminal part AtxA were found...
Ammodytoxin (Atx), an sPLA2 (secretory phospholipase A2), binds to g and e isoforms of porcine 14-3-3 proteins in vitro. are evolutionarily conserved eukaryotic regulatory involved a variety biological processes, including cell-cycle regulation. We have now shown that Atx yeast with affinity similar for the mammalian isoforms. Thus Saccharomyces cerevisiae can be used as model cell, which lacks endogenous phospholipases A2, assess vivo relevance this interaction. was expressed cells...
Following the finding that ammodytoxin (Atx), a neurotoxic secreted phospholipase A2 (sPLA2) in snake venom, binds specifically to protein disulfide isomerase (PDI) vitro we show these proteins also interact living rat PC12 cells are able internalize this group IIA (GIIA) sPLA2. Atx and PDI co-localize both differentiated non-differentiated cells, as shown by fluorescence microscopy. Based on model of complex between yeast (yPDI), three-dimensional human (hPDI) was constructed. The binding...
Presynaptic- or β-neurotoxicity of secreted phospholipases A