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


Team of work

Tricerri, María Alejandra
Principal Investigator
aletricerri@yahoo.com
Ramella, Nahuel
Investigator
nramella@gmail.com
Rosu, silvana
Investigator
silvirosu85@gmail.com
Gisonno, Romina
Research Fellow
rominagisonno@gmail.com
Gaddi, Gisela
Research Fellow
gisemg87@hotmail.com
Finarelli, Gabriela Sandra 
Support Staff
gabisanfin@yahoo.com.ar


Collaborators from other institutions

International

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

Sánchez, Susana
Universidad de Concepción, Concepción, Chile

National


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.

 

Publications

 

  • 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

  • Decreased OxLDL uptake and cholesterol efflux in THP1 cells elicited by cortisol and by cortisone through11β-hydroxysteroid dehydrogenase type 1.
    Ledda, A; Gonzalez, M. C; Gulfo, J; Díaz, L.  I; Ramella, N; Toledo, J. D; Garda, H. A; Grasa, M; Esteve, M.
    2015.
    Atherosclerosis. , Amsterdam: ELSEVIER IRELAND LTD. ISSN 0021-9150

  • 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

Book - Book chapters

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

Awards

  • “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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