A5077258710- Endoplasmic Reticulum Stress and Disease
- Heat shock proteins research
- Galectins and Cancer Biology
- Diabetes and associated disorders
- Protein Interaction Studies and Fluorescence Analysis
- Pancreatic function and diabetes
- Ion Transport and Channel Regulation
- Protease and Inhibitor Mechanisms
- Diabetes Treatment and Management
- Proteoglycans and glycosaminoglycans research
- Adenosine and Purinergic Signaling
- Advanced Glycation End Products research
- Diabetes Management and Research
- Blood properties and coagulation
- Blood Coagulation and Thrombosis Mechanisms
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Mitochondrial Function and Pathology
- Calpain Protease Function and Regulation
- Glycosylation and Glycoproteins Research
- Erythrocyte Function and Pathophysiology
- ATP Synthase and ATPases Research
- Protein Hydrolysis and Bioactive Peptides
- Membrane-based Ion Separation Techniques
- Coenzyme Q10 studies and effects
- Computational Drug Discovery Methods
University of Padua
2008-2021
Grp94 is involved in the regulation of a restricted number proteins and represents potential target host diseases, including cancer, septic shock, autoimmune chronic inflammatory conditions, diabetes, coronary thrombosis, stroke. We have recently identified novel allosteric pocket located N-terminal binding site that can be used to design ligands with 2-log selectivity over other Hsp90 paralogs. Here we perform extensive SAR investigations this ligand series rationalize affinity paralog...
Canrenone, a spironolactone metabolite, was tested for its possible effects on (Na+-K+) adenosine triphosphatase (ATPase) activity [Mg++-dependent, (Na+-K+)-activated ATP phosphohydrolase (E.C.3.6.1.3) and ouabain interaction with the enzyme. Canrenone competitively antagonized binding of [3H]ouabain to (Na+-K+)ATPase inhibited activity. The multiple inhibition technique used demonstrate that canrenone is partial inhibitor (Na+-K+)ATPase, mutually exclusive respect ouabain. Comparative...
The glucose-regulated protein94 (Grp94) has been found in complexes with IgG plasma of Type 1 (T1) diabetic subjects; however, the pathogenetic meaning Grp94-IgG not yet elucidated. To shed light on nature and structure these vivo, we conducted a proteomic analysis both T1 subjects healthy control subjects. purified from was submitted to 2D PAGE followed by Western blotting mass analysis. Grp94 detected all but linked its N-terminus heavy chain. Mass chain that binds also vitro, forming...
While the mechanism by which Grp94 displays its chaperone function with client peptides in cell has been elucidated extensively, much less is known about nature and properties of how can engage binding to proteins once it exposed on surface or liberated extra-cellular milieu, as occurs pathological conditions. In this work, we wanted investigate molecular aspects structural characteristics complexes that forms human IgG, posing attention influence glycosylation might have capacity...
Glucose-regulated protein94 (Grp94), the most represented endoplasmic reticulum (ER)-resident heat shock protein (HSP), is a tumor antigen shared by different types of solid and hematological tumors. The tumor-specific feature Grp94 its translocation from ER to cell surface where it displays pro-oncogenic functions. This un-physiological location has important implications for both pathology anti-tumor therapy. We wanted address question whether could be measured as liquid marker in cancer...
Among substances which may prove useful in preventing or reducing the progression of glycooxidative modifications proteins, heparin plays a unique role. To elucidate mechanism whereby favourably influence protein structure during glycation, human serum albumin (HSA) was glycated with both 25 and 50 m glucose absence presence 12 µg·mL −1 low‐molecular‐mass heparin. Glycation caused: (a) fluorescence emission excitation spectra consistent covalent attachment to protein; (b) significant...
We previously demonstrated that plasma of type 1 diabetic patients contains antibodies complexed irreversibly with Grp94 also display proteolytic activity. In this work, we wanted to test whether obtained from may convey an inflammatory risk on vascular cells. To aim, IgG were purified the Protein-G column individual eight patients, and then tested HUVECs measure effects cell growth morphologic changes at different incubation times. The fractions contained a significant amount Fab/(Fab)2,...
The Bacillus Calmette-Guérin (BCG) vaccine is known to have protective effects not only against tuberculosis but also other unrelated infectious diseases caused by different pathogens. Several epidemiological studies documented the beneficial influence of BCG in reducing both susceptibility and severity SARS-CoV-2 infection. protective, non-specific vaccination would be related an antigen-independent enhancement innate immunity, termed trained immunity. However, knowledge that heat shock...
Both unfractionated and fractionated, low‐molecular‐mass heparins were tested on human serum albumin in the absence presence of glucose at concentrations similar to those frequently found diabetic hyperglycaemic patients, ascertain whether heparin interfered with each other affecting conformation albumin. Reproducible results obtained both when used equal masses, but not molar concentrations, suggesting a crucial role amount saccharide units determining observed effects. Spectroscopic...
Changes in plasma renin activity (PRA) were monitored six mildly hypertensive men after intravenous doses, seven separate experiments, of placebo, digoxin, potassium canrenoate, canrenoate with fur osemide, furo semide and osemide digoxin. Potassium has been used as a rapid source canrenone, which recently shown to be competitive antagonist ouabain at its Na-K-ATPase receptor site. infusion reversed the hyporeninemic effect This result taken evidence that: (1) antialdosteronic drugs can also...
Grp94 is the main endoplasmic reticulum-resident heat shock protein (HSP) that besides chaperoning native proteins, displays important modulatory effects on both innate and adaptive immune response. Since knowledge of a direct influence humoral response lacking, in this work we tested effect Ig secretion from peripheral blood mononuclear cells (PBMCs) five normal volunteers. The concentration secreted medium after incubation 15 days was found increased dose-dependent manner presence Grp94,...
Extracellular Glucose-regulated protein94 (Grp94) is linked to pathological conditions disrupting the obligatory intracellular location of this Heat Shock Protein (HSP). In plasma, Grp94 IgG in complexes that drive adverse effects on vascular cells and are biomarker gastro-intestinal cancer. By blocking ATP site different HSPs, purine-scaffold inhibitors used as promising anti-cancer compounds, but their vasculature not known.We tested capacity two inhibitors, PU-H71 PU-WS13, prevent binding...