GSEA of mouse and human mitochondriomes reveals fatty acid oxidation in astrocytes

The prevalent view in neuroenergetics is that glucose is the main brain fuel, with neurons being mostly oxidative and astrocytes glycolytic. Evidence supporting that astrocyte mitochondria are functional has been overlooked. Here we sought to determine what is unique about astrocyte mitochondria by performing unbiased statistical comparisons of the mitochondriome in astrocytes and neurons. Using MitoCarta, a compendium of mitochondrial proteins, together with transcriptomes of mouse neurons and astrocytes, we generated cell-specific databases of nuclear genes encoding for mitochondrion proteins, ranked according to relative expression. Standard and in-house Gene Set Enrichment Analyses (GSEA) of five mouse transcriptomes revealed that genes encoding for enzymes involved in fatty acid oxidation (FAO) and amino acid catabolism are consistently more expressed in astrocytes than in neurons. FAO and oxidative-metabolism-related genes are also up-regulated in human cortical astrocytesversus the whole cortex, and in adult astrocytes versus fetal astrocytes. We thus present the first evidence of FAO in human astrocytes. Further, as shown in vitro, FAO coexists with glycolysis in astrocytes and is inhibited by glutamate. Altogether, these analyses provide arguments against the glucose-centered view of energy metabolism in astrocytes and reveal mitochondria as specialized organelles in these cells

Lipid droplet biogenesis induced by stress involves triacylglycerol synthesis that depends on group VIA phospholipase A2

This work investigates the metabolic origin of triacylglycerol (TAG) formed during lipid droplet (LD) biogenesis induced by stress. Cytotoxic inhibitors of fatty acid synthase induced TAG synthesis and LD biogenesis in CHO-K1 cells, in the absence of external sources of fatty acids. TAG synthesis was required for LD biogenesis and was sensitive to inhibition and down-regulation of the expression of group VIA phospholipase A2 (iPLA2-VIA). Induction of stress with acidic pH, C2-ceramide, tunicamycin, or deprivation of glucose also stimulated TAG synthesis and LD formation in a manner dependent on iPLA2-VIA. Overexpression of the enzyme enhanced TAG synthesis from endogenous fatty acids and LD occurrence. During stress, LD biogenesis but not TAG synthesis required phosphorylation and activation of group IVA PLA2 (cPLA2α). The results demonstrate that iPLA2-VIA provides fatty acids for TAG synthesis while cPLA2α allows LD biogenesis. LD biogenesis during stress may be a survival strategy, recycling structural phospholipids into energy-generating substrates

CREB decreases astrocytic excitability by modifying subcellular calcium fluxes via the sigma-1 receptor

Altres ajuts: La Marató de TV3 (TV3-20141430)Astrocytic excitability relies on cytosolic calcium increases as a key mechanism, whereby astrocytes contribute to synaptic transmission and hence learning and memory. While it is a cornerstone of neurosciences that experiences are remembered, because transmitters activate gene expression in neurons, long-term adaptive astrocyte plasticity has not been described. Here, we investigated whether the transcription factor CREB mediates adaptive plasticity-like phenomena in astrocytes. We found that activation of CREB-dependent transcription reduced the calcium responses induced by ATP, noradrenaline, or endothelin-1. As to the mechanism, expression of VP16-CREB, a constitutively active CREB mutant, had no effect on basal cytosolic calcium levels, extracellular calcium entry, or calcium mobilization from lysosomal-related acidic stores. Rather, VP16-CREB upregulated sigma-1 receptor expression thereby increasing the release of calcium from the endoplasmic reticulum and its uptake by mitochondria. Sigma-1 receptor was also upregulated in vivo upon VP16-CREB expression in astrocytes. We conclude that CREB decreases astrocyte responsiveness by increasing calcium signalling at the endoplasmic reticulum-mitochondria interface, which might be an astrocyte-based form of long-term depression

Group IVA phospholipase A2 is necessary for the biogenesis of lipid droplets

Lipid droplets (LD) are organelles present in all cell types, consisting of a hydrophobic core of triacylglycerols and cholesteryl esters, surrounded by a monolayer of phospholipids and cholesterol. This work shows that LD biogenesis induced by serum, by long-chain fatty acids, or the combination of both in CHO-K1 cells was prevented by phospholipase A2 inhibitors with a pharmacological profile consistent with the implication of group IVA cytosolic phospholipase A2 (cPLA2α). Knocking down cPLA2α expression with short interfering RNA was similar to pharmacological inhibition in terms of enzyme activity and LD biogenesis. A Chinese hamster ovary cell clone stably expressing an enhanced green fluorescent protein-cPLA2α fusion protein (EGFP-cPLA2) displayed higher LD occurrence under basal conditions and upon LD induction. Induction of LD took place with concurrent phosphorylation of cPLA2α at Ser505. Transfection of a S505A mutant cPLA2α showed that phosphorylation at Ser505 is key for enzyme activity and LD formation. cPLA2α contribution to LD biogenesis was not because of the generation of arachidonic acid, nor was it related to neutral lipid synthesis. cPLA2α inhibition in cells induced to form LD resulted in the appearance of tubulo-vesicular profiles of the smooth endoplasmic reticulum, compatible with a role of cPLA2α in the formation of nascent LD from the endoplasmic reticulum

Revista española de pedagogía

Resumen basado en el de la publicaciónSe analiza las aportaciones del profesor E. W. Eisner a la luz de los cambios del siglo XX al XXI. A pesar del gran impacto internacional de las propuestas del profesor Eisner, se evidencia una falta de estudios unitarios sobre su labor. Se pretende dar una visión de conjunto, ontológica y unitaria con la finalidad de cohesionar los ámbitos en los que tuvo su principal incidencia y sacar conclusiones sobre su legado. Se aborda el perfil del profesor Eisner, tanto en lo personal como profesional, para crear un paradigma de profesor universitario necesario y completo, justificándolo en las vertientes de: docente, investigadora y generador de políticas culturales. Como conclusión y evaluación a las críticas de su trabajo,se valora su capacidad de revisar y aceptar nuevos enfoques, a la vez que su gran habilidad por anticipar necesidades que acaban siendo innovaciones educativas.Biblioteca de Educación del Ministerio de Educación, Cultura y Deporte; Calle San Agustín, 5 - 1 planta; 28014 Madrid; Tel. +34917748000; [email protected]

Las aportaciones de E. W. Eisner a la educación: un profesor paradigmático como docente, investigador y generador de políticas culturales

El artículo pretende analizar las aportaciones del profesor E. W. Eisner a la luz de los cambios del siglo XX al XXI. A pesar del gran impacto internacional de las propuestas del profesor Eisner, se evidencia una falta de estudios unitarios sobre su labor. Se pretende dar una visión de conjunto, ontológica y unitaria con la finalidad de cohesionar los ámbitos en los que tuvo su principal incidencia y sacar conclusiones sobre su legado. Abordamos el perfil del profesor Eisner, tanto en lo personal como profesional, para crear un paradigma de profesor universitario necesario y completo, justificándolo en las vertientes de: docente, investigadora y generador de políticas culturales. Como conclusión y evaluación a las críticas de su trabajo, valoramos su capacidad de revisar y aceptar nuevos enfoques, a la vez que su gran habilidad por anticipar necesidades que acaban siendo innovaciones educativas

Las aportaciones de E. W. Eisner en la educación: un profesor paradigmático como docente, investigador y generador de políticas culturales

Sobre les aportacions d' E. W. Eisner a l' educaci

Activació de la fosfolipasa C per receptors acoblats a proteïnes G en cultius de neurones granulars de cerebel : paper modulador del calci /

Descripció del recurs: el 25 d'octubre de 201