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Dive into the research topics where M. Alejandra Tricerri is active.

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Featured researches published by M. Alejandra Tricerri.


The International Journal of Biochemistry & Cell Biology | 2009

Human apolipoprotein A–I binds amyloid-β and prevents Aβ-induced neurotoxicity

Andrea C. Paula-Lima; M. Alejandra Tricerri; Jordano Brito-Moreira; Theresa R. Bomfim; Fabio Ferreira de Oliveira; Margaret H. Magdesian; Lea T. Grinberg; Rogerio Panizzutti; Sergio T. Ferreira

Aggregates of the amyloid-beta peptide (Abeta) play a central role in the pathogenesis of Alzheimers disease (AD). Identification of proteins that physiologically bind Abeta and modulate its aggregation and neurotoxicity could lead to the development of novel disease-modifying approaches in AD. By screening a phage display peptide library for high affinity ligands of aggregated Abeta(1-42), we isolated a peptide homologous to a highly conserved amino acid sequence present in the N-terminus of apolipoprotein A-I (apoA-I). We show that purified human apoA-I and Abeta form non-covalent complexes and that interaction with apoA-I affects the morphology of amyloid aggregates formed by Abeta. Significantly, Abeta/apoA-I complexes were also detected in cerebrospinal fluid from AD patients. Interestingly, apoA-I and apoA-I-containing reconstituted high density lipoprotein particles protect hippocampal neuronal cultures from Abeta-induced oxidative stress and neurodegeneration. These results suggest that human apoA-I modulates Abeta aggregation and Abeta-induced neuronal damage and that the Abeta-binding domain in apoA-I may constitute a novel framework for the design of inhibitors of Abeta toxicity.


PLOS ONE | 2011

Human Apolipoprotein A-I-Derived Amyloid: Its Association with Atherosclerosis

Nahuel Alberto Ramella; Omar J. Rimoldi; Eduardo Daniel Prieto; Guillermo Schinella; Susana A. Sanchez; M. Jaureguiberry; M. E. Vela; Sergio T. Ferreira; M. Alejandra Tricerri

Amyloidoses constitute a group of diseases in which soluble proteins aggregate and deposit extracellularly in tissues. Nonhereditary apolipoprotein A-I (apoA-I) amyloid is characterized by deposits of nonvariant protein in atherosclerotic arteries. Despite being common, little is known about the pathogenesis and significance of apoA-I deposition. In this work we investigated by fluorescence and biochemical approaches the impact of a cellular microenvironment associated with chronic inflammation on the folding and pro-amyloidogenic processing of apoA-I. Results showed that mildly acidic pH promotes misfolding, aggregation, and increased binding of apoA-I to extracellular matrix elements, thus favoring protein deposition as amyloid like-complexes. In addition, activated neutrophils and oxidative/proteolytic cleavage of the protein give rise to pro amyloidogenic products. We conclude that, even though apoA-I is not inherently amyloidogenic, it may produce non hereditary amyloidosis as a consequence of the pro-inflammatory microenvironment associated to atherogenesis.


Biochimica et Biophysica Acta | 2010

Lipid packing determines protein-membrane interactions: challenges for apolipoprotein A-I and high density lipoproteins.

Susana A. Sanchez; M. Alejandra Tricerri; Giulia Ossato; Enrico Gratton

Protein and protein-lipid interactions, with and within specific areas in the cell membrane, are critical in order to modulate the cell signaling events required to maintain cell functions and viability. Biological bilayers are complex, dynamic platforms, and thus in vivo observations usually need to be preceded by studies on model systems that simplify and discriminate the different factors involved in lipid-protein interactions. Fluorescence microscopy studies using giant unilamellar vesicles (GUVs) as membrane model systems provide a unique methodology to quantify protein binding, interaction, and lipid solubilization in artificial bilayers. The large size of lipid domains obtainable on GUVs, together with fluorescence microscopy techniques, provides the possibility to localize and quantify molecular interactions. Fluorescence Correlation Spectroscopy (FCS) can be performed using the GUV model to extract information on mobility and concentration. Two-photon Laurdan Generalized Polarization (GP) reports on local changes in membrane water content (related to membrane fluidity) due to protein binding or lipid removal from a given lipid domain. In this review, we summarize the experimental microscopy methods used to study the interaction of human apolipoprotein A-I (apoA-I) in lipid-free and lipid-bound conformations with bilayers and natural membranes. Results described here help us to understand cholesterol homeostasis and offer a methodological design suited to different biological systems.


Biochimica et Biophysica Acta | 2002

Folding and stability of the C-terminal half of apolipoprotein A-I examined with a Cys-specific fluorescence probe

Andrea K Behling Agree; M. Alejandra Tricerri; Kirsten Arnvig McGuire; Shaomin Tian; Ana Jonas

Apolipoprotein A-I (apoA-I) has important physiologic roles in reverse cholesterol transport, as a component of HDL; however, apoA-I also exists in lipid-poor or lipid-free forms that are key intermediates in HDL metabolism and acceptors of lipids from cells. The aim of this study was to examine the structure and stability of the central and C-terminal regions of lipid-free apoA-I. To this end, five Cys mutants of proapoA-I were constructed and expressed in Escherichia coli: V119C, A124C, A154C, A190C, and A232C. These mutants were specifically labeled with 6-acryloyl-2-dimethylaminonaphthalene (acrylodan, AC) and were examined by CD spectroscopy and a variety of fluorescence methods. The results showed that the introduction of Cys residues and their covalent labeling with AC did not affect the overall structure and stability of apoA-I. However, AC fluorescence properties revealed that different segments of the central and C-terminal half of apoA-I have distinct folding and stability properties. From fluorescence energy transfer data, average distances between the N-terminal region containing Trp residues and the various AC locations were obtained. The current results, together with previously published observations, led to the construction of a three-dimensional model for the folding of lipid-free apoA-I.


PLOS ONE | 2015

Amyloidogenic propensity of a natural variant of human apolipoprotein A-I: stability and interaction with ligands.

Silvana Antonia Rosu; Omar J. Rimoldi; Eduardo Daniel Prieto; Lucrecia M. Curto; José M. Delfino; Nahuel Alberto Ramella; M. Alejandra Tricerri

A number of naturally occurring mutations of 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 of the Arg173Pro point mutation in apoA-I on the structure, stability, and aggregation propensity, as well as on the ability to bind to putative ligands. Our results indicate that the mutation induces a drastic loss of stability, and a lower efficiency to bind to phospholipid vesicles at physiological pH, which could determine the observed higher tendency to aggregate as pro-amyloidogenic complexes. Incubation under acidic conditions does not seem to induce significant desestabilization or aggregation tendency, neither does it contribute to the binding of the mutant to sodium dodecyl sulfate. While the binding to this detergent is higher for the mutant as compared to wt apoA-I, the interaction of the Arg173Pro variant with heparin depends on pH, being lower at pH 5.0 and higher than wt under physiological pH conditions. We suggest that binding to ligands as heparin or other glycosaminoglycans could be key events tuning the fine details of the interaction of apoA-I variants with the micro-environment, and probably eliciting the toxicity of these variants in hereditary amyloidoses.


Pathophysiology | 2018

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?

Nahuel Alberto Ramella; I Andújar; José Luis Ríos; Silvana Antonia Rosu; M. Alejandra Tricerri; Guillermo Schinella

The cascade of molecular events leading to Human apolipoprotein A-I (apoA-I) amyloidosis is not completely understood, not even the pathways that determine clinical manifestations associated to systemic protein deposition in organs such as liver, kidney and heart. About twenty natural variants of apoA-I were described as inducing amyloidosis, but the mechanisms driving their aggregation and deposition are still unclear. We previously identified that the mutant Gly26Arg but not Lys107-0 induced the release of cytokines and reactive oxygen species from cultured RAW 264.7 murine macrophages, suggesting that part of the pathogenic pathway could elicit of an inflammatory signal. In this work we gained deep insight into this mechanism and determined that Gly26Arg induced a specific pro-inflammatory cascade involving activation of NF-κB and its translocation into the nucleus. These findings suggest that some but not all apoA-I natural variants might promote a pro-oxidant microenvironment which could in turn result in oxidative processing of the variants into a misfolded conformation.


Protein Journal | 2017

Learning from Synthetic Models of Extracellular Matrix; Differential Binding of Wild Type and Amyloidogenic Human Apolipoprotein A-I to Hydrogels Formed from Molecules Having Charges Similar to Those Found in Natural GAGs

Silvana Antonia Rosu; Leandro Toledo; Bruno F. Urbano; Susana A. Sanchez; Graciela C. Calabrese; M. Alejandra Tricerri

Among other components of the extracellular matrix (ECM), glycoproteins and glycosaminoglycans (GAGs) have been strongly associated to the retention or misfolding of different proteins inducing the formation of deposits in amyloid diseases. The composition of these molecules is highly diverse and a key issue seems to be the equilibrium between physiological and pathological events. In order to have a model in which the composition of the matrix could be finely controlled, we designed and synthesized crosslinked hydrophilic polymers, the so-called hydrogels varying the amounts of negative charges and hydroxyl groups that are prevalent in GAGs. We checked and compared by fluorescence techniques the binding of human apolipoprotein A-I and a natural mutant involved in amyloidosis to the hydrogel scaffolds. Our results indicate that both proteins are highly retained as long as the negative charge increases, and in addition it was shown that the mutant is more retained than the Wt, indicating that the retention of specific proteins in the ECM could be part of the pathogenicity. These results show the importance of the use of these polymers as a model to get deep insight into the studies of proteins within macromolecules.


Journal of Lipid Research | 2002

Interaction of apolipoprotein A-I in three different conformations with palmitoyl oleoyl phosphatidylcholine vesicles

M. Alejandra Tricerri; Susana A. Sanchez; Cristina Arnulphi; Diane M. Durbin; Enrico Gratton; Ana Jonas


Journal of Lipid Research | 2005

Visualization and analysis of apolipoprotein A-I interaction with binary phospholipid bilayers

M. Alejandra Tricerri; Juan Domingo Toledo; Susana A. Sanchez; Theodore L. Hazlett; Enrico Gratton; Ana Jonas; Horacio A. Garda


Biophysical Journal | 2005

Interaction of human apolipoprotein A-I with model membranes exhibiting lipid domains.

Cristina Arnulphi; Susana A. Sanchez; M. Alejandra Tricerri; Enrico Gratton; Ana Jonas

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Dive into the M. Alejandra Tricerri's collaboration.

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Nahuel Alberto Ramella

National University of La Plata

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Omar J. Rimoldi

National University of La Plata

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Silvana Antonia Rosu

National Scientific and Technical Research Council

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Enrico Gratton

University of California

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Sergio T. Ferreira

Federal University of Rio de Janeiro

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Eduardo Daniel Prieto

National University of La Plata

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Guillermo Schinella

National University of La Plata

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José M. Delfino

University of Buenos Aires

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Lucrecia M. Curto

University of Buenos Aires

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