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 ONE HEALTH / Noncommunicable chronic diseases / Cancer

Laboratory of lipid metabolism and cancer

Regulation of cellular glycerolipid synthesis

Work team

Principal InvestigatorGonzález Baró

González Baró, María del R.

Investigator
mgbaro@med.unlp.edu.ar

Cattaneo, Elizabeth ReneeCattaneo

Investigator
ecattaneo@med.unlp.edu.ar

Montanaro, Mauro AldoMontanaro

Investigator
mmontanaro@med.unlp.edu.ar

Moscoso, VerónicaMoscoso

Research Fellow
vmoscoso@med.unlp.edu.ar

Martiarena, OrianaMartiarena

Research Fellow

Collaborators from other institutions

Coleman, Rosalind
Department of Nutrition and Pediatrics, University of North Carolina, Chapel Hill, NC, USA.

Ballsels, Rosa Erra
UBA. Universidad de Buenos Aires. Buenos Aires. Argentina.

Cabrerizo, Franco
Instituto Tecnológico de Chascomús. Chascomús. Provincia de Buenos Aires. Argentina.

Abba, Martín
Centro de Investigaciones Inmunológicas Básicas y Aplicadas. Universidad Nacional de La Plata. La Plata. Provincia de Buenos Aires. Argentina.

Rabassa, Martín
Centro de Investigaciones Inmunológicas Básicas y Aplicadas. Universidad Nacional de La Plata. La Plata. Provincia de Buenos Aires. Argentina.

Lacunza, Ezequiel
Centro de Investigaciones Inmunológicas Básicas y Aplicadas. Universidad Nacional de La Plata. La Plata. Provincia de Buenos Aires. Argentina.

Line overview

Role of the glycerol-3 phosphate acyltransferase in the synthesis of cellular glycerolipids.

The first step in the synthesis of glycerolipids in mammalian cells is catalyzed by glycerol-3-phosphate acyltransferase (GPAT). Four genes that encode isoforms of this enzyme have been cloned. They can be expressed in different tissues and in different subcellular sites. In fact, we are interested in the role of GPAT2; this isoform in mainly expressed in rat, mouse and human testis. We have previously demonstrated that GPAT2 is expressed mainly in sperm cells, but when this gene is overexpressed in CHO-K1 cells, the synthesis and storage of triacylglycerols and cell proliferation increase.
Our objective is to determine substrate specificity of GPAT2, and then identify its metabolites derived from its activity, promoting cell proliferation. Another objective is to know in which kind of cell in the sperm line this gene is expressed as well as to analyze this expression in different tumor cells.
To carry out this project, we use the classical biochemical techniques such as measurement of enzymatic activities by means of radioactive substrates, isolation techniques, analysis of lipids and fatty acids. The GPAT2 protein was detected by Western blot and immunohistochemistry, and mRNA by PCR (quantitative in real time and in situ hybridization). Also, we have studied the heterologous GPAT2 overexpression in culture cells.
We have determined that GPAT2 is a gene which mRNA is only expressed in primary spermatocytes under normal conditions; it seems to be overexpressed in non differenciated tumor cells. Some metabolites derived from its enzymatic activity are rich in arachidonate, and they may function as signals for proliferation and/or cell survival.

Fatty acid metabolism in the outer mitochondrial membrane.

Synthesis downregulation and triacylglycerol catabolism produce serious health problems as obesity and diabetes type 2. The first and limiting step in the TAG synthesis is catalyzed by glycerol-3-phosphate acyltransferase (GPAT). The mitochondrial isoform GPAT1 is related to TAG synthesis, and its cellular localization is related to carnitine palmitoyltransferase 1 (CPT1) that catalyzes the limiting step of fatty acid β-oxidation, and to some isoforms of acyl-CoA synthetases of long chain fatty acids (ACSL) which reaction product is the substrate of both GPAT1 and CPT1. It was hypothesized that in mitochondria channeling of acyl-CoA substrates to biosynthetic or oxidative processes involves protein-protein interactions. Our aim is: 1) Characterize the oligomeric structure of GPAT1; 2) Analyze the role of different isoforms of ACSL and CPT1 in the supply and availability of acyl-CoA substrates for GPAT1. In order to achieve objective 1, techniques of chemical crosslinking either in culture cells or in mitochondrias isolated from rat liver, will be used. Protein complexes, containing GPAT1 by immunoprecipitation, will be isolated in order to identify the interacting proteins by mass spectrometry. Concerning objective 2, we will study the reciprocal regulation of GPAT1 and CPT1 overexpressing inactive mutants of these enzymes in cell culture, as well as substrate channeling from different ACSL isoforms in models of overexpression, subexpression and inactivation of each isoform localized by GPAT1 and CPT1. Direct interaction of GPAT1 and CPT1 with ACSL will be tested by labeling transfer or Western blotting. The present studies will get insight into synthesis regulation and lipid degradation: how protein-protein interactions regulate substrate flow and products in mitochondria.
LAlso, certain pathological conditions concerning obesity and diabetes mellitus type 2 that lead, in part, to the metabolic syndrome, will be elucidated.


DNA cleavage mechanism by metal complexes of Cu(II), Zn(II) and VO(IV) with a schiff-base ligand.
Rodríguez, María R.; Lavecchia, Martín J.; Parajón-Costa, Beatriz S.; González-Baró, Ana C.; González-Baró, María R.; Cattáneo, Elizabeth R.
2021. Biochimie. Paris: ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER,- . vol. 186, p. 43-50. ISSN 0300-9084

Metodologías para la detección de SARS-CoV-2 y análisis de carga viral mediante RT-PCR cuantitativa.
Jaquenod De Giusti, Carolina; Montanaro, Mauro; Mencucci, Maria Victoria; Canzoneri, Romina; Orlowski, Alejandro; Santana, Marianela; Pereyra, Erica; Kraemer, Mauricio Horacio; Pedríni, Nicolás; González Baro, María; Vila Petroff, Martin; Aiello, Alejandro; Abba, Martin; Lavarías, Sabrina María Luisa; Moscoso, Verónica; Costantini, Noelian; Francini, Flavio; Garda, H.
2020. Innovación y desarrollo tecnológico y social (idts). La Plata: Universidad Nacional de La Plata. vol. 2, n° 2, p. 1-14
doi.org/10.24215/26838559e013

Triacylglycerol synthesis directed by glycerol-3-phosphate acyltransferases -3 and -4 is required for lipid droplet formation and the modulation of the inflammatory response during macrophage to foam cell transition.
Quiroga, Ivana Y.; Pellon-Maison, Magali; González, Marina C.; Coleman, Rosalind A.; González Baro, Maria R.
2020. Atherosclerosis. ELSEVIER IRELAND LTD. ISSN 0021-9150
doi.org/10.1016/j.atherosclerosis.2020.11.022

Problematización acerca de la articulación entre extensión, docencia e investigación en la UNLP y su repercusión en la formación univeritaria.
Fusé Santiago; Henning, María Florencia; Karpenko Wilman, Ingrid Denise; Pellon Maison, Magalí.
2020. Trayectorias Universitarias. La Plata: Universidad Nacional de La Plata, vol. 6, n° e036, p. 79-91. ISSN 2469-0090
dx.doi.org/10.24215/24690090e036

Glycerol-3-phosphate acyltransferases 3 and 4 direct glycerolipid synthesis and affect functionality in activated macrophages.
Quiroga, I. Y.; Pellon-Maison, M.; Suchanek, A. L.; Coleman, R.A.; González Baro, M. R.
2019: Biochemical journal. Londres: PORTLAND PRESS LTD, vol. 476, p. 85-99. ISSN 0264-6021
doi.org/10.1042/BCJ20180381

Small non-coding RNA landscape is modified by GPAT2 silencing in MDA-MB-231 cells.
Lacunza, E; Montanaro, M. A; Salvati, A. M; Memoli, D; Rizzo, F; Henning, M. F; Quiroga, I. Y; Guillou, H; Abba, M. C; Gonzalez-Baro, M. R; Weisz, A; Pellon Maison, M.
2018. Oncotarget. Impact Journals, vol. 9, p. 28141-28154. ISSN 1949-2553

Mitochondrial acyltransferases and glycerophospholipid metabolism.
Gonzalez Baro, M. R; Coleman, R. A.
2017. Biochimica et biophysica acta-molecular and cell biology of lipids. Amsterdam: ELSEVIER SCIENCE BV. vol. 1862, p. 49-55. ISSN 1388-1981

Glycerol-3-phosphate acyltransferase 2 expression modulates cell roughness and membrane permeability: an Atomic Force Microscopy study.
Cattáneo, E. R; Prieto, E. D; García Fabiani. M. B; Montanaro, M. A; Herve, G; Gonzalez Baro, M. R.
2017. Plos one. San Francisco: PUBLIC LIBRARY SCIENCE. ISSN 1932-6203

Glycerol-3-phosphate acyltransferase 2 is essential for normal spermatogenesis.
Garcia-Fabiani, M. B; Montanaro, M. A; Stringa, P; Lacunza, E; Cattaneo, E. R; Santana, M; Pellon-Maison, M; Gonzalez-Baro, M. R.
2017. Biochemical journal: PORTLAND PRESS LTD, vol. 474, n° 18, p. 3093-3107. ISSN 0264-6021

Methylation of the Gpat2 promoter regulates transient expression during mouse spermatogenesis.
García Fabiani, M. B; Montanaro, M. A; Lacunza, E; Cattaneo, E. R; Coleman, R. A; Pellon Maison, M; Gonzalez-Baró; M. R.
2015. Biochemical Journal. Londres: PORTLAND PRESS LTD, vol. 471, p. 211-220. ISSN 0264-6021

Glycerol-3-phosphate acyltranferase-2 behaves as a cancer testis gene and promotes growth and tumorigenicity of the breast cancer mda-mb-231 cellline.
Pellon Maison, M; Montanaro, M. A; Lacunza, E; Garcia Fabiani, M. B; Soler, M; Cattaneo, E; Quiroga, I. Y; Abba, M; Coleman, R; Gonzalez Baro, M del R.
2014. Plos one. San Francisco: PUBLIC LIBRARY SCIENCE, vol. 9, ISSN 1932-6203

Apolipoprotein A-I Helsinki promotes intracellular acyl-CoA cholesterol acyltransferase (ACAT) protein accumulation.
Toledo, J. D; Garda, H. A; Cabaleiro, L. V; Cuellar, A; Pellón Maison, M; González Baró, M; Gonzalez M. C.
2013. Molecular and cellular biochemistry. New York: SPRINGER. vol. 377, n° 1-2, p. 197-205. ISSN 0300-8177

Rol de la isoforma 2 de la glicerol-3-fosfato aciltransfersa 2 en el metabolismo lipídico testicular.
Cattaneo, E. R; Pellon Maison, M; Gonzalez-Baro, M. R.
2013. Acta Bioquímica Clínica Latinoamericana. La Plata: Federación Bioquímica Provincia Buenos Aires, vol. 47, p. 315-325. ISSN 0325-2957

Glycerol-3-Phosphate Acyltransferase-2 Is Expressed in.
Cattaneo, E. R; Pellon Maison, M; Rabassa, M. E; Lacunza, E; Coleman, R. A; González-Baro, M. R.
2012. Plos One. San Francisco: Public Library Science, vol. 7, p. 1-11

Photosensitization of DNA by bcarbolines: Kinetic analysis and Organic Biomolecular Chemistry.
González, M. M; Vignoni, M; Pellon-Maison, M; Ales-Gandolfo, M. A; González-Baro, M. R; Erra-Balsells, R; Bernd Epe; Cabrerizo, F. M.
2012. Cambridge: Royal Soc Chemistry, vol. 10, p. 1807-1819

Nuclear receptors and hepatic lipidogenic enzymes response to a dyslipidemic sucrose rich diet and its revertion by fish oil n-3 polyunsaturated fatty acids.
Hein, G. J; Bernasconi, A.M; Montanaro, M.A; Pellon-Maison M; Finarelli, G.S; Chicco, A; Lombardo,Y. B; Brenner, R. R.
2010. American journal of physiology-endocrinology and metabolism. Amer Physiological Soc. vol. 298, p. 429-439

Photosensitized cleavage of plasmidic DNA by norharmane, a naturally occurring beta-carboline.
González, M. M; Pellon-Maison, M; Ales-Gandolfo, M. A; González-Baro, M. R; Erra-Balsells, R; Cabrerizo, F. M.
2010. Organic & biomolecular chemistry. Royal Soc Chemistry. vol.8, p. 2543 - 2552

Macrobrachium borellii hepatopancreas contains a mitochondrial glycerol-3-phosphate acyltransferase which initiates triacylglycerol biosynthesis.
Pellon Maison, M; García, F; Cattaneo, E; Coleman, R. A; González-Baro, M. R.
2009. Lipids. AOCS Press, vol. 44, p. 337-344

Cloning and functional characterization of a novel mitochondrial Nethylmaleimide-sensitive glycerol-3-phosphate acyltransferase (GPAT2).
Wang, S; Lee, D. P; Gong, N; Schwerbrock, N. M. J; Mashek. D. G; González - Baro, M. R; Stapleton, C; Li, L. O; Lewin, T. M; Coleman, R. A.
2007. Archives of biochemistry and biophysics. Elsevier. vol. 465, p. 347-358

Role of liver X receptor, insulin and peroxisome proliferator activated receptor alpha on in vivo desaturase modulation of unsaturated fatty acid biosynthesis.
Montanaro, M. A; González, M. S; Bernasconi, A. M; Brenner, R. R.
2007. Lipids. American Oil Chemists Society. vol. 42, p. 197-210

Mitochondrial glycerol-3-P acyltransferase 1 is most active in outer mitochondrial membrane but not in mitochondrial associated vesicles (MAV).
Pellon-Maison, M; Montanaro, M. A; Coleman, R. A; Gonzalez-Baró M. R.
2007. Biochimica et biophysica acta-molecular and cell biology of lipids. Elsevier. vol. 1771, p. 830-838

Lipid Synthesis and Transport in Shrimps.
Garcia, C. F; Gonzalez-Baró, M.
2013. Hauppauge, NY: Nova Science Publishers, p. 71-94. ISBN 978-1-62417-317-2



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