A5056184136- Protease and Inhibitor Mechanisms
- Lysosomal Storage Disorders Research
- Cellular transport and secretion
- Inflammasome and immune disorders
- Glycogen Storage Diseases and Myoclonus
- Alzheimer's disease research and treatments
- Autophagy in Disease and Therapy
- Mitochondrial Function and Pathology
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Peptidase Inhibition and Analysis
- Folate and B Vitamins Research
- S100 Proteins and Annexins
- Advanced Glycation End Products research
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune Response and Inflammation
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Trace Elements in Health
- Iron Metabolism and Disorders
- Cell death mechanisms and regulation
- interferon and immune responses
- Adenosine and Purinergic Signaling
- Biochemical and Structural Characterization
- Heme Oxygenase-1 and Carbon Monoxide
- Immune cells in cancer
Jožef Stefan Institute
2013-2024
National Institute of Chemistry
2015
University of Ljubljana
1994
Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases localized in the nucleus and cytosol. Loss-of-function mutations stefin gene (CSTB) were reported patients with Unverricht-Lundborg disease (EPM1). We have identified interaction between nucleosomes, specifically histones H2A.Z, H2B, H3. In synchronized T98G cells, co-immunoprecipitated histone H3, predominantly G(1) phase cell cycle. B-deficient mouse embryonic fibroblasts entered S earlier than wild type fibroblasts....
Abstract The cysteine peptidase cathepsin B is important in thyroid physiology by being involved prohormone processing initiated the follicular lumen and completed endo-lysosomal compartments. However, has also been localized to extrafollicular space therefore suggested promote invasiveness metastasis carcinomas through, e.g., ECM degradation. In this study, immunofluorescence biochemical data from subcellular fractionation revealed that B, its single- two-chain forms, endo-lysosomes...
To estimate the prognostic value of cathepsins B, H, L, D and stefins A B in head neck carcinoma, their concentrations cytosols primary tumours adjacent normal tissue were measured (cathepsins A, 45, cathepsin L 24 H 21 patients). Median significantly higher tumour than (B D: p < 0.0001; L: = 0.004); concentration was (p 0.001). Concentrations either stefin did not differ between tissue. laryngeal non-laryngeal tissues. The difference statistically significant for 0.045), marginally 0.07)....
The pore-forming protein perforin is synthesized as an inactive precursor in natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), becomes active when a short C-terminal peptide cleaved within acidic lysosome-like granules. Although it was shown more than decade ago that this cleavage pH dependent can be inhibited by the generic cysteine cathepsin inhibitor E-64d, no protease capable of processing C terminus has been identified. Neither known whether single responsible or inbuilt...
Protein aggregation is central to most neurodegenerative diseases, as shown by familial case studies and animal models. A modified ‘amyloid cascade’ hypothesis for Alzheimer's disease states that prefibrillar oligomers, also called amyloid‐β‐derived diffusible ligands or globular are the responsible toxic agent. It has been proposed these oligomeric species, amyloid‐β, β 2 ‐microglobulin prion fragments, exert toxicity forming pores in membranes, initiating a cascade of detrimental events...
To contribute to the question of putative role cystatins in Alzheimer disease and neuroprotection general, we studied interaction between human stefin B (cystatin B) amyloid-β-(1–40) peptide (Aβ). Using surface plasmon resonance electrospray mass spectrometry were able show a direct two proteins. As an interesting new fact, that binding Aβ is oligomer specific. The dimers tetramers B, which bind Aβ, are domain-swapped as judged from structural studies. Consistent with results, same oligomers...
Innate immune responses are tightly regulated to avoid excessive activation and subsequent inflammatory damage the host, interleukin‐10 (IL‐10) plays a crucial role in preventing inflammation. Stefin B (cystatin B) is an endogenous inhibitor of cysteine proteinases. In stefin B‐deficient bone marrow‐derived macrophages (BMDMs), we detected increase induction LPS‐induced pro‐inflammatory signal nitric oxide (NO) but decreased IL‐10 expression. The phosphorylation ERK p38 MAP‐kinases was...
Cystatin F is a unique member of the cystatin family cysteine protease inhibitors, which synthesized as an inactive dimer and it activated by N-terminal cleavage in endolysosomes. It expressed cells immune system: myeloid involved target cell killing: natural killer (NK) cytotoxic T (CTLs). Upon activation NK with interleukin 2 (IL-2), was found upregulated co-localized granules cathepsin C (CatC) CatV. However, inhibits CatC only when its part processed. Although could inhibit both CatV...
Amyloid-induced toxicity is a well-known phenomenon but the molecular background remains unclear. One hypothesis relates to amyloid–membrane interactions, predicting that amyloid oligomers make pores into membranes. Therefore, and membrane interaction of prefibrillar aggregates individual non-pathological yet highly amyloidogenic protein human stefin B (cystatin B) was examined. By monitoring caspase-3 activity by testing cell viability, we showed lag phase obtained at pH 5 3 were toxic...
Background . Protein aggregation is a major contributor to the pathogenic mechanisms of human neurodegenerative diseases. Mutations in CSTB (cystatin B) gene [StB (stefin B)] cause EPM1 (progressive myoclonus epilepsy type 1), an syndrome with features neurodegeneration and increased oxidative stress. Oligomerization StB mammalian cells have recently been reported. It has also observed that overexpressed after seizures certain conditions, which could potentially lead its aggregation. Human...
Cystatin C is a potent cysteine protease inhibitor that plays an important role in various biological processes including cancer, cardiovascular diseases and neurodegenerative diseases. However, the of CstC inflammation still unclear. In this study we demonstrated cystatin C-deficient mice were significantly more sensitive to lethal LPS-induced sepsis. We further showed increased caspase-11 gene expression enhanced processing pro-inflammatory cytokines IL-1β IL-18 KO bone marrow-derived...
It has been suggested that the lysosomal proteinases cathepsin B, L and D participate in tumour invasion metastasis. Whereas for cathepsins B role of active enzyme processes confirmed, was to support progression via its pro-peptide, rather than by proteolytic activity. In this study we have compared presence ras-transformed human breast epithelial cells (MCF-10A neoT) with their ability invade matrigel. cell line high expression all three detected immunofluorescence microscopy. The effect...