Browsing by Author "Cortés Mora, Víctor Antonio"
Now showing 1 - 6 of 6
Results Per Page
Sort Options
- ItemBalance energético en ratones lipodistróficos con deleción del gen Agpat2 y su respuesta a la infusión de leptina(2022) Mejía Rivera, Luisa Fernanda; Cortés Mora, Víctor Antonio; Pontificia Universidad Católica de Chile. Escuela de MedicinaLa lipodistrofia congénita generalizada (LCG) está definida por reducción grave de tejido adiposo y complicaciones metabólicas como hiperfagia, hipoleptinemia, y resistencia insulínica. En este estudio utilizamos ratones Agpat2-/-, modelos de LCG. Como hipótesis se propone que la hiperfagia en ratones Agpat2-/- vs ratones normales (WT) se asocia a mayor gasto energético (GE) y mantención del peso corporal por oxidación aumentada de ácidos grasos (AG), representada con valores de cuociente respiratorio (RER). La infusión con leptina normaliza estas variables y revierte la oxidación aumentada de AG. Se analizaron dos estudios previos, el primer estudio utilizó ratones Agpat2-/- (infundidos con leptina) y ratones WT. En el segundo estudio se investigaron ratones Agpat2-/- (infundidos con leptina). Los ratones Agpat2-/- tuvieron un consumo de agua y alimento mayor (15 y 48%) que los ratones WT. El consumo de O2, producción de CO2 y GE también fue mayor en 1,43, 0,34 y 1,32% (P³0,05, N=4). En cuanto al RER de ratones Agpat2-/-, presentó valores promedio de ∽0,93, mientras que los ratones WT presentaron valores de RER de ∽0,97 (sin significancia estadística). La infusión con leptina permite que el consumo de alimento y agua se normalice al mismo nivel que en ratones WT. En el segundo estudio la infusión de leptina resultó en una reducción de 5,35% y de 8,81% en la ingesta de alimento y agua a 72 horas de iniciada la infusión. El GE en la cuarta semana de infusión presentó disminución de 8,14 y 4,81% en luz y oscuridad, en comparación con los valores pre infusión. Conclusiones: Los ratones Agpat2-/- presentan hiperfagia asociada a gasto energético elevado en comparación con ratones WT, las oscilaciones diarias de RER fueron menores en ratones Agpat2-/-, sugiriendo inflexibilidad metabólica. La infusión con leptina revirtió el GE aumentado y la hiperfagia en ratones Agpat2-/-.
- ItemFluoxetine Impairs Insulin Secretion without Modifying Extracellular Serotonin Levels in MIN6 β-cells(2015) Cataldo Bascuñan, Luis Rodrigo; Cortés Mora, Víctor Antonio; Mizgier Rojas, María Luisa; Aranda, E.; Mezzano, Diego; Olmos Coelho, Pablo Roberto; Galgani Fuentes, José; Suazo, J.; Santos Martín, José Luis
- ItemNO production and eNOS phosphorylation induced by epinephrine through the activation of β-adrenoceptors(2009) Figueroa, Xavier; Cortés Mora, Víctor Antonio; Huidobro-Toro, Juan Pablo.; Poblete, Inés; Fernández Acevedo, Ricardo Hernán; Pedemonte Trewhela, Juan CristóbalEpinephrine plays a key role in the control of vasomotor tone; however, the participation of the NO/cGMP pathway in response to β-adrenoceptor activation remains controversial. To evaluate the involvement of the endothelium in the vascular response to epinephrine, we assessed NO production, endothelial NO synthase phosphorylation, and tissue accumulation of cGMP in the perfused arterial mesenteric bed of rat. Epinephrine elicited a concentration-dependent increase in NO (EC50 of 45.7 pM), which was coupled to cGMP tissue accumulation. Both NO and cGMP production were blocked by either endothelium removal (saponin) or NO synthase inhibition (Nω-nitro-l-arginine). Blockade of β1- and β2-adrenoceptors with 1 μM propranolol or β3-adrenoceptor with 10 nM SR 59230A displaced rightward the concentration-NO production curve evoked by epinephrine. Selective stimulation of β1-, β2-, or β3-adrenoceptors also resulted in NO and cGMP production. Propranolol (1 μM) inhibited the rise in NO induced by isoproterenol or the β2-adrenoceptor agonists salbutamol, terbutaline, or fenoterol. Likewise, 10 nM SR 59230A reduced the effects of the β3-adrenoceptor agonists BRL 37344, CGP 12177, SR 595611A, or pindolol. The NO production induced by epinephrine and BRL 37344 was associated with the activation of the phosphatidylinositol 3-kinase/Akt pathway and phosphorylation of eNOS in serine 1177. In addition, in anaesthetized rats, bolus administration of isoproterenol, salbutamol, or BRL 37344 produced NO-dependent reductions in systolic blood pressure. These findings indicate that β1-, β2-, and β3-adrenoceptors are coupled to the NO/cGMP pathway, highlighting the role of the endothelium in the vasomotor action elicited by epinephrine and related β-adrenoceptor agonists.
- ItemNpc1 deficiency in the C57BL/6J genetic background enhances Niemann–Pick disease type C spleen pathology(2011) Parra Cares, Julio Alejandro; Klein, Andres D.; Castro, Juan Francisco; Morales France, María Gabriela; Mosqueira Montero, Matías José; Valencia Araya, Ilse; Cortés Mora, Víctor Antonio; Rigotti Rivera, Attilio; Zanlungo Matsuhiro, SilvanaNiemann–Pick type C (NPC) disease is an autosomal recessive neurovisceral lipid storage disorder. The affected genes are NPC1 and NPC2. Mutations in either gene lead to intracellular cholesterol accumulation. There are three forms of the disease, which are categorized based on the onset and severity of the disease: the infantile form, in which the liver and spleen are severely affected, the juvenile form, in which the liver and brain are affected, and the adult form, which affects the brain. In mice, a spontaneous mutation in the Npc1 gene originated in the BALB/c inbred strain mimics the juvenile form of the disease. To study the influence of genetic background on the expression of NPC disease in mice, we transferred the Npc1 mutation from the BALB/c to C57BL/6J inbred background. We found that C57BL/6J-Npc1−/− mice present with a much more aggressive form of the disease, including a shorter lifespan than BALB/c-Npc1−/− mice. Surprisingly, there was no difference in the amount of cholesterol in the brains of Npc1−/− mice of either mouse strain. However, Npc1−/− mice with the C57BL/6J genetic background showed striking spleen damage with a marked buildup of cholesterol and phospholipids at an early age, which correlated with large foamy cell clusters. In addition, C57BL/6J Npc1−/− mice presented red cell abnormalities and abundant ghost erythrocytes that correlated with a lower hemoglobin concentration. We also found abnormalities in white cells, such as cytoplasmic granulation and neutrophil hypersegmentation that included lymphopenia and atypias. In conclusion, Npc1 deficiency in the C57BL6/J background is associated with spleen, erythrocyte, and immune system abnormalities that lead to a reduced lifespan.
- ItemStimulation of the sympathetic perimesenteric arterial nerves releases neuropeptide Y potentiating the vasomotor activity of noradrenaline: Involvement of neuropeptide Y-Y1 receptors(1997) Donoso Gomien, María Verónica; Brown, Nelson; Carrasco, C.; Cortés Mora, Víctor Antonio; Fournier, A.; García-Huidobro Toro, Juan PabloNeuropeptide Y (NPY) appears to be involved in the sympathetic regulation of vascular tone. To assess the putative role of NPY in mesenteric circulation, the release and biological effect of NPY were examined after electrical stimulation of perimesenteric arterial nerves. Nerve stimulation with trains of 2-30 Hz increased the perfusion pressure of the arterially perfused rat mesenteric bed in a frequency- and time-dependent fashion. Trains of 15-30 Hz significantly displaced to the left, approximately threefold, the noradrenaline (NA)-induced pressor concentration-response curve, in addition to increasing significantly its efficacy. Perfusion with 10 nM exogenous NPY mimicked the electrical stimulation effect, causing a threefold leftward shift of the NA concentration-response curve and increasing the maximal NA response. These effects were antagonized by 100 nM BIBP 3226, indicating the activity of NPY-Y1 receptors. Electrical stimulation of the perimesenteric nerves released immunoreactive NPY (ir- NPY) in a frequency-dependent fashion; the ir-NPY coelutes with synthetic NPY as confirmed by HPLC. Both the electrically induced pressor response and the calcium-dependent release of NPY were obliterated in preparations perfused with 1 μM guanethidine or in rats pretreated intravenously for 48 h with 6- hydroxydopamine, thus revealing the sympathetic origin of these phenomena. Only a small proportion of the total NPY content in the perimesenteric arterial nerves is released after electrical stimulation. Chromatographic studies of the physiological sources of the ir-NPY support that NPY fragments are generated via peptidase degradation. The present findings demonstrate that NPY is released from the perimesenteric arterial sympathetic nerves and acts, via the activation of NPY-Y1 receptors, as the mediator responsible for the potentiation of NA's effect on perfusion pressure in the isolated rat mesenteric bed.