Disfunción mitocondrial como mediador de muerte celular inducida por ketamina en células neuronales: expresión del RNAm de UCP2
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ItemHemocytes of the ribbed mussel Aulacomya atra atra from Nuevo Gulf (Chubut) as biomarkers of oxidative stress(Nova Science Publishers, Inc, 2018)Bivalve mollusks exposed to a wide variety of natural and anthropogenic environmental changes are widely used as sentinels. These factors can cause an imbalance between the generation and elimination of reactive oxygen species (ROS) and reactive nitrogen species (RNS), leading to an oxidative stress that is manifested by alterations of the antioxidant defense system and/or oxidative damage. The hemocytes constitute the immune system in bivalves, and cell death processes have been recently described as part of the mechanism of defense against various pathogens and contaminants. Previous studies showed a higher content of trace metals Fe and Cd in the gills and digestive gland of the Aulacomya atra atra from Folías Wreck (impacted area) than from Punta Cuevas (control area). In order to compare oxidative stress conditions in bivalves obtained from both sites, we evaluated the production of ROS and oxidative stress biomarkers in hemocytes from the A. atra atra during the month of September of 2015. The results obtained by flow cytometry, using MitoSox as probe, showed that superoxide anion was 58% higher in bivalve’s hemocytes from Folías Wreck than in those from the reference place Punta Cuevas. The oxidation of the dye 2´ 7´ dichlorofluorescein diacetate (DCFH-DA), as a general indicator of oxidative stress, showed a 14% increase in bivalve’s hemocytes from Folías Wreck, as compared to hemocytes from Punta Cuevas. Thiobarbituric acid reactive substances (TBARS) content showed no differences between hemocytes from animals isolated from both locations. In addition, the content of lipid radical measured by Electron Spin Resonance increased 2.1 fold in the hemocytes from Folías Wreck samples as compared to the level obtained in hemocytes from bivalves collected from Punta Cuevas. The oxidized/depleted cardiolipin was 16% higher in samples obtained from Folías Wreck than in Punta Cuevas. Based on these results, it can be concluded that hemocytes from the ribbed mussel A. atra atra could be used as a model to evaluate oxidative stress induced by pollutants or other environmental stressors.
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ItemLactic acid transport mediated by aquaporin-9 : implications on the pathophysiology of preeclampsia(Frontiers, 2021)Aquaporin-9 (AQP9) expression is significantly increased in preeclamptic placentas. Since feto-maternal water transfer is not altered in preeclampsia, the main role of AQP9 in human placenta is unclear. Given that AQP9 is also a metabolite channel, we aimed to evaluate the participation of AQP9 in lactate transfer across the human placenta. Explants from normal term placentas were cultured in low glucose medium with or without L-lactic acid and in the presence and absence of AQP9 blockers (0.3 mM HgCl2 or 0.5 mM Phloretin). Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and lactate dehydrogenase release. Apoptotic indexes were analyzed by Bax/Bcl-2 ratio and Terminal Deoxynucleotidyltransferase-Mediated dUTP Nick-End Labeling assay. Heavy/large and light/small mitochondrial subpopulations were obtained by differential centrifugation, and AQP9 expression was detected by Western blot. We found that apoptosis was induced when placental explants were cultured in low glucose medium while the addition of L-lactic acid prevented cell death. In this condition, AQP9 blocking increased the apoptotic indexes. We also confirmed the presence of two mitochondrial subpopulations which exhibit different morphologic and metabolic states. Western blot revealed AQP9 expression only in the heavy/large mitochondrial subpopulation. This is the first report that shows that AQP9 is expressed in the heavy/large mitochondrial subpopulation of trophoblasts. Thus, AQP9 may mediate not only the lactic acid entrance into the cytosol but also into the mitochondria. Consequently, its lack of functionality in preeclamptic placentas may impair lactic acid utilization by the placenta, adversely affecting the survival of the trophoblast cells and enhancing the systemic endothelial dysfunction.
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ItemAlcohol hangover induces nitric oxide metabolism changes by impairing NMDA receptor-PSD95-nNOS pathway(Elsevier, 2021-5-5)Alcohol hangover is defined as the combination of mental and physical symptoms experienced the day after a single episode of heavy drinking, starting when blood alcohol concentration approaches zero. We previously evidenced increments in free radical generation and an imbalance in antioxidant defences in non-synaptic mitochondria and synaptosomes during hangover. It is widely known that acute alcohol exposure induces changes in nitric oxide (NO) production and blocks the binding of glutamate to NMDAR in central nervous system. Our aim was to evaluate the residual effect of acute ethanol exposure (hangover) on NO metabolism and the role of NMDA receptor-PSD95-nNOS pathway in non-synaptic mitochondria and synaptosomes from mouse brain cortex. Results obtained for the synaptosomes fraction showed a 37% decrease in NO total content, a 36% decrease in NOS activity and a 19% decrease in nNOS protein expression. The in vitro addition of glutamate to synaptosomes produced a concentration-dependent enhancement of NO production which was significantly lower in samples from hangover mice than in controls for all the glutamate concentrations tested. A similar patter of response was observed for nNOS activity being decreased both in basal conditions and after glutamate addition. In addition, synaptosomes exhibited a 64% and 15% reduction in NMDA receptor subunit GluN2B and PSD-95 protein expression, respectively. Together with this, glutamate-induced calcium entry was significant decreased in synaptosomes from alcohol-treated mice. On the other hand, in non-synaptic mitochondria, no significant differences were observed in NO content, NOS activity or nNOS protein expression. The expression of iNOS remained unaltered in synaptosomes and non-synaptic mitochondria. Here we demonstrated that hangover effects on NO metabolism are strongly evidenced in synaptosomes probably due to a disruption in NMDAR/PSD- 95/nNOS pathway.