A5048783571- Amyloidosis: Diagnosis, Treatment, Outcomes
- Alzheimer's disease research and treatments
- Diabetes, Cardiovascular Risks, and Lipoproteins
- Lipid Membrane Structure and Behavior
- Protein Structure and Dynamics
- Cholesterol and Lipid Metabolism
- Lipoproteins and Cardiovascular Health
- Sphingolipid Metabolism and Signaling
- Protein Interaction Studies and Fluorescence Analysis
- Lipid metabolism and biosynthesis
- Peroxisome Proliferator-Activated Receptors
- Trace Elements in Health
- Protein Kinase Regulation and GTPase Signaling
- Pancreatitis Pathology and Treatment
- Metabolomics and Mass Spectrometry Studies
- Force Microscopy Techniques and Applications
- Connective tissue disorders research
- Cholinesterase and Neurodegenerative Diseases
- Spectroscopy and Quantum Chemical Studies
- Drug Transport and Resistance Mechanisms
- Surfactants and Colloidal Systems
- Blood properties and coagulation
- Atherosclerosis and Cardiovascular Diseases
- Parathyroid Disorders and Treatments
- Machine Learning in Bioinformatics
Institute of Science and Technology Austria
2024
Biochemistry Research Institute of La Plata
2010-2023
Consejo Nacional de Investigaciones Científicas y Técnicas
2010-2023
Universidad Nacional de La Plata
2011-2023
University of Illinois Urbana-Champaign
2000-2005
DePaul University
2004
University of Illinois Chicago
2004
Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits nonvariant protein atherosclerotic arteries. Despite being common, little known about the pathogenesis significance apoA-I deposition. In this work we investigated fluorescence biochemical approaches impact cellular microenvironment associated with chronic inflammation on folding pro-amyloidogenic...
The folding and organization of apolipoprotein A-I (apoA-I) in discoidal, high-density lipoprotein (HDL) complexes with phospholipids are not yet completely resolved. For about 20 years, it was generally accepted that the amphipathic helices apoA-I lie parallel to acyl chains ("picket fence" model). However, based on X-ray crystal structure a large, lipid-free fragment apoA-I, "belt model" recently proposed. In this model, two antiparallel molecules extended circular arrangement...
A number of naturally occurring mutations human apolipoprotein A-I (apoA-I) have been associated with hereditary amyloidoses. The molecular mechanisms involved in amyloid-associated pathology remain largely unknown. Here we examined the effects Arg173Pro point mutation apoA-I on structure, stability, and aggregation propensity, as well ability to bind putative ligands. Our results indicate that induces a drastic loss lower efficiency phospholipid vesicles at physiological pH, which could...
Two new Cys mutants of proapolipoprotein A-I, D9C and A232C, were created expressed in Escherichia coli systems. Specific labeling with the thiol-reactive fluorescence probe, 6-acryloyl-2-dimethylaminonaphthalene (acrylodan), was used to study structural organization dynamic properties extreme regions human apolipoprotein A-I (apoA-I) lipid-free lipid-bound states. Spectroscopic approaches, including circular dichroism various methods, examine mutant proteins their covalent adducts probe....
Interactions of apolipoprotein A-I (apoA-I) with cell membranes appear to be important in the initial steps reverse cholesterol transport. The objective this work was examine effect three distinct conformations apoA-I (lipid-free and 78 Å or 96 reconstituted high density lipoproteins, rHDL) on its ability bind to, abstract lipids from, palmitoyl oleoyl phosphatidylcholine membrane vesicles (small unilamellar vesicles, SUV, giant GUV). molecular interactions were observed by two-photon...
The interaction of lipid-free apolipoprotein A-I (apoA-I) with small unilamellar vesicles (SUVs) 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) and without free cholesterol (FC) was studied by isothermal titration calorimetry circular dichroism spectroscopy. Parameters reported are the affinity constant (Ka), number protein molecules bound per vesicle (n), enthalpy change (ΔH°), entropy (ΔS°), heat capacity (ΔCp°). binding process apoA-I to SUVs POPC plus 0−20% (mole) FC exothermic between...
Experimental evidence has suggested that plasma membrane (PM)-associated signaling and hence cell metabolism viability depend on lipid composition organization. The aim of the present work is to develop a model study endogenous polyunsaturated fatty acids (PUFAs) effect PM properties analyze its influence cholesterol (Chol) homeostasis. We have previously shown by using line over-expressing stearoyl-CoA-desaturase, organization coordinate cellular pathways involved in Chol efflux different...
Apolipoprotein A-I (apoA-I) interaction with specific cell lipid domains was suggested to trigger cholesterol and phospholipid efflux. We analyzed here apoA-I dimyristoylphosphatidylcholine/distearoylphosphatidylcholine (DMPC/DSPC) bilayers at a temperature showing phase coexistence. Solid liquid-crystalline were visualized by two-photon fluorescence microscopy on giant unilamellar vesicles (GUVs) labeled 6-dodecanoyl-2-dimethyl-amino-naphthalene (Laurdan). A decrease of vesicle size...
The cascade of molecular events leading to Human apolipoprotein A-I (apoA-I) amyloidosis is not completely understood, even the pathways that determine clinical manifestations associated systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants apoA-I were described inducing amyloidosis, but mechanisms driving their aggregation are still unclear. We previously identified mutant Gly26Arg Lys107-0 induced release cytokines reactive oxygen species from...
Although copper (Cu) is an essential trace metal for cells, it can induce harmful effects as participates in the Fenton reaction. Involuntary exposure to Cu overload much more common than expected and has been linked with neurodegeneration, particularly Alzheimer's disease (AD) evidenced by a positive correlation between free plasma severity of disease. It suggested that imbalance alters cholesterol (Chol) homeostasis high membrane Chol promotes amyloidogenic processing amyloid precursor...
Apolipoprotein A-I (apoA-I) has a key function in the reverse cholesterol transport. However, aggregation of apoA-I single point mutants can lead to hereditary amyloid pathology. Although several studies have tackled biophysical and structural consequences introduced by these mutations, there is little information addressing relationship between evolutionary features that contribute behavior apoA-I. We combined studies, silico mutagenesis molecular dynamics (MD) simulations provide...