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

Background and aims: The transition of macrophage to foam cells is a major hallmark of early stage atherosclerotic lesions. This process is characterized by the accumulation of large cytoplasmic lipid droplets containing large quantities of cholesterol esters (CE), triacylglycerol (TAG) and phospholipid (PL). Although cholesterol and CE metabolism during foam cell formation has been broadly studied, little is known about the role of the glycerolipids (TAG and PL) in this context. Here we studied the contribution of glycerolipid synthesis to lipid accumulation, focusing specifically on the first and rate-limiting enzyme of the pathway: glycerol-3-phosphate acyltransferase (GPAT). Methods: We used RAW 264.7 cells and bone marrow derived macrophages (BMDM) treated with oxidized LDL (oxLDL). Results: We showed that TAG synthesis is induced during the macrophage to foam cell transition. The expression and activity of GPAT3 and GPAT4 also increased during this process, and these two isoforms were required for the accumulation of cell TAG and PL. Compared to cells from wildtype mice after macrophage to foam cell transition, Gpat4−/− BMDM released more pro-inflammatory cytokines and chemokines, suggesting that the activity of GPAT4 could be associated with a decrease in the inflammatory response, probably by sequestering signaling precursors into lipid droplets. Conclusions: Our results provide evidence that TAG synthesis directed by GPAT3 and GPAT4 is required for lipid droplet formation and the modulation of the inflammatory response during the macrophage-foam cell transition.Fil: Quiroga, Ivana Yoseli. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Pellon Maison, Magali. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Gonzalez, Marina Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; ArgentinaFil: Coleman, Rosalind A.. University of North Carolina; Estados UnidosFil: Gonzalez Baro, Maria del Rosario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner". Universidad Nacional de la Plata. Facultad de Ciencias Médicas. Instituto de Investigaciones Bioquímicas de La Plata "Prof. Dr. Rodolfo R. Brenner"; Argentin

Vibrational spectra of the α-MIIC2O4.2H2O oxalato complexes, with MII = Co, Ni, Zn

The infrared and Raman spectra of the α-MIIC2O4⋅2H2O oxalate complexes with MII = Co, Ni and Zn were recorded and briefly discussed on the basis of their structural peculiarities. The IR spectrum of a partially deuterated sample of α-ZnC2O4⋅2H2O is also discussed, reinforcing some of the performed assignments in the lower energy spectral region.Se registraron los espectros de infrarrojo y Raman de los oxalato-complejos α-MIIC2O4⋅2H2O con MII = Co, Ni, Zn y se los discute brevemente en base a sus peculiaridades estructurales. Asimismo, se discute el espectro IR de una muestra parcialmente deuterada de α-ZnC2O4⋅2H2O el que permitió reforzar algunas de las asignaciones realizadas en la zona espectral de baja energía.Fil: Wladimirsky, Alejandra. Universidad Tecnológica Nacional; ArgentinaFil: Palacios, Daniel. Universidad Tecnológica Nacional; ArgentinaFil: D Antonio, María C.. Universidad Tecnológica Nacional; Argentina. Universidad Nacional de la Patagonia Austral; ArgentinaFil: Gonzalez Baro, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Baran, Enrique José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin

The Value of ICT and the Students' Heterogeneity

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Structural and Spectroscopic Behavior of double Metal Oxalates from the first transition Metal Series

A series of double metal oxalates of stoichiometry MM´(C2O4)2.4H2O (with MM´= MnCo, MnNi, MnZn, CoNi, CoCu, CoZn, NiCu, NiZn and CuZn have been prepared and characterized. Their structural behavior was investigated by means of X-ray powder diffractometry, showing a strong structural analogy to the orthorhombic, so-called beta-modification, of the related simple oxalato complexes of composition MC2O4.2H2O. The vibrational spectroscopic behavior of the double metal oxalates was investigated by infrared and Raman spectroscopy. The results clearly confirmed the close structural analogies between the MM´(C2O4)2.4H2O, alfa-MC2O4.2H2O and beta-MC2O4.2H2O series of complexes.Fil: D’Antonio, María C.. Universidad Nacional de la Patagonia Austral. Unidad Académica Río Gallegos; ArgentinaFil: Torres, María Marta. Universidad Nacional de la Patagonia Austral. Unidad Académica Río Gallegos; ArgentinaFil: Palacios, Daniel Alejandro. Universidad Nacional de la Patagonia Austral. Unidad Académica Río Gallegos; ArgentinaFil: Gonzalez Baro, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Barone, Vicente Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Baran, Enrique José. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin

ChaLearn Looking at People Challenge 2014: Dataset and Results

This paper summarizes the ChaLearn Looking at People 2014 challenge data and the results obtained by the participants. The competition was split into three independent tracks: human pose recovery from RGB data, action and interaction recognition from RGB data sequences, and multi-modal gesture recognition from RGB-Depth sequences. For all the tracks, the goal was to perform user-independent recognition in sequences of continuous images using the overlapping Jaccard index as the evaluation measure. In this edition of the ChaLearn challenge, two large novel data sets were made publicly available and the Microsoft Codalab platform were used to manage the competition. Outstanding results were achieved in the three challenge tracks, with accuracy results of 0.20, 0.50, and 0.85 for pose recovery, action/interaction recognition, and multi-modal gesture recognition, respectively

Macrobrachium borellii Hepatopancreas Contains a Mitochondrial Glycerol-3-Phosphate Acyltransferase Which Initiates Triacylglycerol Biosynthesis

Mammals express four isoforms of glycerol-3-phosphate acyltransferase (GPAT). The mitochondrial isoform GPAT1 may have been the acyltransferase that appeared first in evolution. The hepatopancreas of the crustacean Macrobrachium borellii has a high capacity for triacylglycerol (TAG) biosynthesis and storage. In order to understand the mechanism of glycerolipid biosynthesis in M. borellii, we investigated its hepatopancreas GPAT activity. In hepatopancreas mitochondria, we identified a GPAT activity with characteristics similar to those of mammalian GPAT1. The activity was resistant to inactivation by SH-reactive N-ethylmaleimide, it was activated by polymyxin-B, and its preferred substrate was palmitoyl-CoA. The reaction products were similar to those of mammalian GPAT1. A 70-kDa protein band immunoreacted with an anti-rat liver GPAT1 antibody. Surprisingly, we did not detect high GPAT specific activity in hepato-pancreas microsomes. GPAT activity in microsomes was consistent with mitochondrial contamination, and its properties were similar to those of the mitochondrial activity. In microsomes, TAG synthesis was not dependent on the presence of glycerol-3 phosphate as a substrate, and the addition of monoacylglycerol as a substrate increased TAG synthesis 2-fold. We conclude that in M. borellii the de novo triacylglycerol biosynthetic pathway can be completed in the mitochondria. In contrast, TAG synthesis in the ER may function via the monoacylglycerol pathway

Synthesis, crystal structure, spectroscopic characterization, DFT calculations and cytotoxicity assays of a new cu(II) complex with an acylhydrazone Ligand derived from thiophene

A new Cu(II) complex is synthetized by the reaction of copper nitrate and a N-acylhydrazone ligand obtained from the condensation of o-vanillin and 2-thiophecarbohydrazide (H2L). The solid-state structure of [Cu(HL)(H2O)](NO3)·H2O, or CuHL for simplicity, was determined by X-ray diffraction. In the cationic complex, the copper center is in a nearly squared planar environment with the nitrate interacting as a counterion. CuHL was characterized by spectroscopic techniques, including solid-state FTIR, Raman, electron paramagnetic resonance (EPR) and diffuse reflectance and solution UV-Vis electronic spectroscopy. Calculations based on the density functional theory (DFT) assisted the interpretation and assignment of the spectroscopic data. The complex does not show relevant antioxidant activity evaluated by the radical cation of 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) method, being even less active than the free ligand as a radical quencher. Cytotoxicity assays of CuHL against three human tumor cell lines, namely MG-63, A549 and HT-29, revealed an important enhancement of the effectiveness as compared with both the ligand and the free metal ion. Moreover, its cytotoxic effect was remarkably stronger than that of the reference metallodrug cisplatin in all cancer cell lines tested, a promissory result in the search for new metallodrugs of essential transition metals.Fil: Rodríguez, María R.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Balsa, Lucia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Piro, Oscar Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: Etcheverría, Gustavo A.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Física La Plata. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Física La Plata; ArgentinaFil: García Tojal, Javier. Universidad de Burgos; EspañaFil: Pis Diez, Reinaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Leon, Ignacio Esteban. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Parajón Costa, Beatriz Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; ArgentinaFil: Gonzalez Baro, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica "Dr. Pedro J. Aymonino". Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Centro de Química Inorgánica "Dr. Pedro J. Aymonino"; Argentin

A novel oxidovanadium(V) compound with an isonicotinohydrazide ligand: A combined experimental and theoretical study and cytotoxity against K562 cells

The interaction of oxidovanadium(V) with INHOVA (the condensation product of isoniazid and o-vanillin) lead to the formation of the ester-like complex [VO(INHOVA)EtO(OH2)]Cl·H2O (1). Crystals suitable for X-ray diffraction methods were obtained. The complex crystallizes as a dimer in the space group P21/c of the monoclinic system. A detailed analysis, including solid-state vibrational spectroscopy and electronic spectroscopy in DMSO solution, was performed for both INHOVA and complex (1). A complete theoretical study based on DFT was also carried out. The calculations were of valuable assistance in the spectra assignments and interpretation. The electrochemical characterization allows determining the redox behavior of INHOVA and complex (1). Cytotoxicity was assayed against the chronic myelogenous leukemia K562 cell line. The IC50 values obtained denote that both the ligand and complex (1) are good candidates for further studies.Fil: Gonzalez Baro, Ana Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica ; ArgentinaFil: Ferraresi Curotto, Verónica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica ; ArgentinaFil: Pis Diez, Reinaldo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica ; ArgentinaFil: Parajón Costa, Beatriz Susana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Química Inorgánica ; ArgentinaFil: Resende, Jackson A. L. C.. Cua/ufmt; . Universidade Federal do Mato Grosso do Sul; BrasilFil: de Paula, Flávia C. S.. Universidade Federal de Minas Gerais; BrasilFil: Pereira Maia, Elene C.. Universidade Federal de Minas Gerais; BrasilFil: Rey, Nicolás A.. Universidade de Sao Paulo; Brasi

Methylation of the Gpat2 promoter regulates transient expression during mouse spermatogenesis

Spermatogenesis is a highly regulated process that involves both mitotic and meiotic divisions, as well as cellular differentiation to yield mature spermatozoa from undifferentiated germinal stem cells. Although Gpat2 was originally annotated as encoding a glycerol-3-phosphate acyltransferase by sequence homology to Gpat1, GPAT2 is highly expressed in testis but not in lipogenic tissues and is not up-regulated during adipocyte differentiation. New data show that GPAT2 is required for the synthesis of piRNAs (piwi-interacting RNAs), a group of small RNAs that protect the germ cell genome from retrotransposable elements. In order to understand the relationship between GPAT2 and its role in the testis, we focused on Gpat2 expression during the first wave of mouse spermatogenesis. Gpat2 expression was analysed by qPCR (quantitative real-time PCR), in situ hybridization, immunohistochemistry and Western blotting. Gpat2 mRNA content and protein expression were maximal at 15 dpp (days post-partum) and were restricted to pachytene spermatocytes. To achieve this transient expression, both epigenetic mechanisms and trans-acting factors are involved. In vitro assays showed that Gpat2 expression correlates with DNA demethylation and histone acetylation and that it is up-regulated by retinoic acid. Epigenetic regulation by DNA methylation was confirmed in vivo in germ cells by bisulfite sequencing of the Gpat2 promoter. Consistent with the initiation of meiosis at 11 dpp, methylation decreased dramatically. Thus, Gpat2 is expressed at a specific stage of spermatogenesis, consistent with piRNA synthesis and meiosis I prophase, and its on–off expression pattern responds predominantly to epigenetic modifications