Study of human apolipoproteín A-I natural variants implicated in amyloidosis

Team of work

Principal InvestigatorTricerri

Tricerri, María Alejandra

Investigator
aletricerri@med.unlp.edu.ar

Ramella, NahuelRamella

Investigator
nramella@med.unlp.edu.ar

Finarelli, Gabriela SandraFinarelli

Professional support staff
CICPBA
gfinarelli@med.unlp.edu.ar

Rosu, Silvana AntoniaRosu

Professional support staff
CONICET
srosu@med.unlp.edu.ar

Collaborators from other institutions

Ferreira, Sergio
Universidad Federal de Rio de Janeiro. Rio de Janeiro. Brasil.

Sánchez, Susana
Universidad de Concepción, Concepción, Chile.

Calabrese, Graciela
Departamento de Ciencias Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Curto, Lucrecia
Departamento de Química Biológica e Instituto de Bioquímica y Biofísica, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina.

Schinella, Guillermo
Cátedra de Farmacología Básica, Facultad de Ciencias Médicas, Universidad Nacional de La Plata. La Plata, Buenos Aires, Argentina.

Prieto, Eduardo
Instituto de Investigaciones Fisicoquímicas Teóricas y Aplicadas (INIFTA), Universidad Nacional de La Plata-CONICET. La Plata, Buenos Aires, Argentina.

Line overview

The risk of loose and “partially unfolded” protein structures as human apolipoprotein A-I (apoA-I) is that they may adopt anomalous conformations, generating insoluble aggregates. In fact, apoA-I fragments can be found in amyloid stores of aortic atherosclerotic plaques as well as in other organs.
The pro-amyloidogenic proteolytic processing may be favored by certain mutations, as Gly26Arg, though neither structural nor environmental factors that trigger it have been deeply investigated.
In order to get insight into the molecular events that favor apoA-I misfolding and aggregation we study, in comparison with the wild type protein, different natural mutants that were detected as inducing amyloidosis in patients.
We analyze environmental factors, especially those related with pro-inflammatory microenvironments (oxidative stress) that favor not only the proteolytic processing but also the anomalous folding. Moreover, we are interested in determining whether protein misfolding can activate the inflammatory cell response and endothelial damage. To do so we have a model of inflammatory response that involves cells of the immune system and endothelial cells.


Interactions of variants of human apolipoprotein A-I with biopolymeric model matrices. Effect of collagen and heparin.
Silvana A Rosú, Joao Aguilar, Bruno F Urbano, Wilson A Tarraga, Nahuel A Ramella, Gabriel S Longo, Gabriela S Finarelli, Susana A Sanchez Donoso, M Alejandra Tricerri.
2023. Arch Biochem Biophys.
doi: 10.1016/j.abb.2023.109805

Evolutionary and structural constraints influencing apolipoprotein A-I amyloid behavior.
Gisonno, Romina A.; Masson, Tomas; Ramella, Nahuel A.; Barrera, Exequiel E.; Romanowski, Víctor; Tricerri, M. Alejandra.
2022: Proteins: structure, function and genetics. WILEY-LISS, DIV JOHN WILEY & SONS INC, 2022 - . vol. 90, n° 1, p. 258-269. ISSN 0887-3585
doi.org/10.1002/prot.26217

Effect of Sublethal Copper Overload on Cholesterol De Novo Synthesis in Undifferentiated Neuronal Cells
Zubillaga Marlene; Rosa Diana; Astiz Mariana; Tricerri Alejandra; Arnal Nathalie.
2022. Acs omega. ACS Omega. vol. 7, n° 29, p. 25022-25030. ISSN 2470-1343
doi.org/10.1021/acsomega.2c00703

Understanding the role of apolipoproteinA-I in atherosclerosis. Post-translational modifications synergize dysfunction?.
Ludovico, Ivo Díaz; Gisonno, Romina A.; González, Marina C.; Garda, Horacio A.; Ramella, Nahuel A.; Tricerri, M. Alejandra.
2021. Biochimica et biophysica acta-general subjects. : ELSEVIER SCIENCE BV - . vol. 1865, n° 1, ISSN 0304-4165

The trophoblast clock controls transport across placenta in mice.
Demarez, Cécile; De Assis, Leonardo Vinicius Monteiro; Krohn, Markus; Ramella, Nahuel; Schwaninger, Markus; Oster, Henrik; Astiz, Mariana.
2021. Development: COMPANY OF BIOLOGISTS LTD,-. vol. 148, n° 8, ISSN 0950-1991

Structural analysis of a natural apolipoprotein A-I variant (L60R) associated with amyloidosis.
Gaddi G; Gisonno R; Rosu S; Curto L. M; Prieto E. D; Schinella G; Finarelli G; Cortez M. F; Bauzá L; Elías E. E; Ramella N; Tricerri M. A.
2020. Archives of biochemistry and biophysics. Amsterdam: ELSEVIERSCIENCE INC, 2020 - . vol. 685, n° 1083, ISSN 0003-9861
doi.org/10.1016/j.abb.2020.108347

Fibrillar conformation of an apolipoprotein AI variant involved in amyloidosis and atherosclerosis.
Gisonno, Romina A.; Prieto, Eduardo D.; Gorgojo, Juan P.; Curto, Lucrecia M.; Rodríguez, M. Eugenia; Rosú, Silvana A.; Gaddi, Gisela M.; Finarelli, Gabriela S.; Cortez, M. Fernanda; Schinella, Guillermo R.; Tricerri, M. Alejandra; Ramella, Nahuel A.
2020. Biochimica et biophysica acta-general subjects. Amsterdam: ELSEVIER SCIENCE BV. vol. 1864, ISSN 0304-4165
doi.org/10.1016/j.bbagen.2020.129515

Data regarding the sensibility to proteolysis of a natural apolipoprotein A-I mutant.
Gaddi, Gisela M.; Gisonno, Romina; Rosu, S. A.; Cortez, M. Fernanda; Finarelli, Gabriela S.; Ramella, N. A; Tricerri, M. A.
2020. Archives of biochemistry and biophysics. Amsterdam: ELSEVIER SCIENCE INC. vol. 31, ISSN 0003-9861
doi.org/10.1016/j.dib.2020.105960

Dataset of the construction and characterization of stable biological nanoparticles.
Gisonno, Romina A.; Tricerri, M. Alejandra; González, Marina C.; Garda, Horacio A.; Ramella, Nahuel A.; Díaz Ludovico, Ivo.
2020. Data in brief. Amsterdam: Elsevier Inc., vol. 33, ISSN 2352-3409
doi.org/10.1016/j.dib.2020.106536

Human apolipoprotein A-I Gly26Arg stimulation of inflammatory responses via NF-kB activation: Potential roles in amyloidosis?.
Ramella, N. A; Andújar, I; Ríos, J. L; Rosú, S. A; Tricerri, M. A; Schinella, G. R.
2018. Pathophysiolog, Elsevier B.V., vol. 25, n° 4, p. 397-404. ISSN 0928-4680

Thiabendazole adsorption on montmorillonite, octadecyltrimethylammonium - and Acremonium sp.-loaded products and their copper complexes.
Gamba, M; Olivelli, M; Gaddi, G; Lazaro Martinez, J; Curutchet, G; Torres Sanchez, R.
2017. Chemical engineering journal. Amsterdam: ELSEVIER SCIENCE SA. vol. 320, p. 11-21. ISSN 1385-8947

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.
Rosú, S. A; Toledo, L; Urbano, B. F; Sanchez, S. A; Calabrese, G. C; Tricerri, M. A.
2017. Protein journal: SPRINGER, 2017. vol. 36, n° 4, p. 374-383. ISSN 1572-3887

Role of cortisol in inflammationtriggered by macrophages exposition to modified LDL.
Toledo, J. D; Montserrat, E; Grasa, M. Del M; Ledda, A; Garda, H. A; Gulfo, J; Díaz, L. I; Ramella, N; Gonzalez, M. C.
2016. Data in brief-journal: Elsevier, vol. 8, p. 251-257

Data related to inflammation and cholesterol deposition triggered by macrophages exposition to modified LDL.
Toledo, J. D; Rafols, M; Grasa, M; Ledda, A; Garda, H. A; Gulfo, J; Diaz, L. I; Ramella, N; Gonzalez, M. C.
2016. Data in brief: Elsevier, vol. 8, p. 251-257

Decreased OxLDL uptake and cholesterol efflux in THP1cells elicited by cortisol and by cortisone through 11b-hydroxysteroid dehydrogenase type 1.
Ledda, A; Gonzalez. M; Gulfo, J; Díaz, L. I; Ramella, N; Toledo, J; Garda, H; Grasa, M; Montserrat, E.
2016. Atherosclerosis. Amsterdam: ELSEVIER IRELAND LTD, vol. 250, p. 84-94. ISSN 0021-9150

Amyloidogenic Propensity of a Natural Variant of Human Apolipoprotein A-I: Stability and Interaction with Ligands.
Rosu, S; Rimoldi, O; Prieto, E; Curto, L; Delfino, J; Ramella, N (*); Tricerri, A (*); (* contribuyeron por igual).
2015. Plos One. San Francisco: PUBLIC LIBRARY SCIENCE. vol. 10, p. 1-17. ISSN 1932-6203

Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models expressing fatty acid desaturases.
Jaureguiberry, M. S; Tricerri, M. A; Sánchez, S. A; Finarelli, G. S; Montanaro, M. A; Prieto, E; Rimoldi, O. J.
2014. Acta Biochimica et Biophysica Sinica. Oxford: OXFORD UNIV PRESS, p. 1-10. ISSN 1005-9628

Role of plasma membrane lipid composition on cellular homeostasis: learning from cell line models over expressing fatty acid desaturases.
Jaureguiberry, M. S; Tricerri, M. A; Sanchez, S. A; Finarelli, G. S; Montanaro, M. A; Prieto, E. D; Rimoldi, O. J.
2014. Acta Biochimica et Biophysica Sinica. Shanghai: ABBS, vol. 46, n° 4, p. 273-282. ISSN 1745-7270

Human Apolipoprotein A-I Natural Variants: Molecular Mechanisms Underlying Amyloidogenic Propensity.
Ramella, N; Schinella, G; Ferreira, S. T; Prieto, E. D; Vela, M E; Rios, J. L; Tricerri, M. A; Rimoldi, O. J.
2012. Plos One. San Francisco: Public Library Science, vol. 7, p. 43755-43766

Laurdan generalized polarization fluctuations measures membrane packing micro-heterogeneity in vivo.
Sanchez, S. A; Tricerri, M. A; Gratton, E.
2012. Proceedings of the National Academy of Sciences of the United States of America. Washington DC, USA: Natl Acad Sciences, vol. 109, n° 9, p. 7314-7319

Characterization of a human apolipoprotein a-I construct expressed in a bacterial system.
Prieto, E. D; Ramella, N; Cuellar, L. A; Tricerri, M. A; Garda, H. A.
2012. Protein journal. Berlin: Springer, vol. 31, n° 8, p. 681-688

Methyl–β-Cyclodextrins preferentially remove cholesterol from the liquid disordered phase in Giant Unilamellar Vesicles.
Sánchez, S. A; Gunther, G; Tricerri, M. A; Gratton, E. J.
2011. J. Memb. Biology (241:1–10 ISSN 0022-2631) Editorial: Springer

Human Apolipoprotein A-I-Derived Amyloid: it’s Association with Atherosclerosis.
Ramella, N. A; Rimoldi, O. J; Prieto, E. D; Schinella, G. R; Sanchez, S. A; Jaureguiberry, M.S; Vela, M.E; Ferreira, S. T; Tricerri, M. A.
2011. PLoS One 6 (7): e22532. eISSN-1932-6203 Epub Jul 19

Lipid packing determines protein membrane interactions: Challenges for.
Sanchez, S. A; Tricerri, M. A; Ossato, G; Gratton, E.
2010. Biochimica et biophysica acta-biomembranes. Elsevier Science BV. vol. 1789, p. 1399 - 1408

Membrane Organization and Regulation of Cellular Cholesterol.
Jaureguiberry, M. S; Tricerri, M. A; Sanchez, S. A; Garda, H. A; Finarelli, G. S; Gonzalez, M. C; Rimoldi. O. J.
2010. Journal of membrane biology. New York: Springer. vol. 234, p. 183 - 194

Human apolipoprotein A-I binds amyloid-ß and prevents Aßinduced neurotoxicity.
Paula-Lima, A. C; Tricerri, M. A; Brito Moreira, J; Bomfim, T. R; Oliveira, F. F; Magdesian, M. H; Gringberg, L. T; Panizzutti, R; Ferreira, S. T.
2009. International Journal of Biochemistry and Cellular Biology. Netherlands: Elsevier, vol. 41, p. 1361 - 1370

The central type Y amphipathic ahelices of apolipoprotein AI are involved in the mobilization of intracellular cholesterol depots.
González, M. C; Toledo, J. D; Tricerri, M. A; Garda, H. A.
2008. Archives of biochemistry and biophysics. Amsterdam: Elsevier, vol. 473, n° 1, p. 34 - 41

Detecting cholesterol changes in Lipid bilayers.
Sanchez, S. A; Tricerri, M. A; Gratton, E.
2008. Bioworld Europe. vol. 1, p. 8 - 11

Interaction of High Density Lipoprotein particles with membranes containing cholesterol. Journal of lipid research.
Sánchez, S. A; Tricerri, M. A; Gratton, E.
2007. American Society for Biochemistry and Molecular Biology. vol. 48, n° 8, p. 1689 - 1700

Desafío de una materia optativa: integrar saberes e inquietudes para una evolución.
Tricerri, M. A; Bussetto, G; Golik, K; Pieroni, M; Pipet, D; Rondan, F. A.
2017. UNLP. La Plata: Universidad Nacional de La Plata, p 61-70. ISBN 978-950-34-1488-0

Modern Research and Educational Topics in Microscopy.
Sánchez, S. A; Tricerri, M. A; Gunther, G; Gratton, E.
2007. Microscopy Book Series.

“Premio SAB al mejor trabajo”
III Congreso Iberoamericano de Biofísica y XXVI Reunión Anual de la Sociedad Argentina de Biofísica. Buenos Aires. Septiembre de 1997.
“Conformation of apolipoprotein A-I in reconstituted lipoprotein particles and particle-membrane interaction. Effect of size and cholesterol”.
Tricerri, M. A; Córsico, B; Toledo, J. D; Garda, H. A; Brenner, R. R.




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