Role of Superoxide Anions in the Redox Changes Affecting the Physiologically Occurring Cu(I)-Glutathione Complex

The physiologically occurring copper-glutathione complex, [Cu(I)-[GSH]2], has the ability to react continually with oxygen, generating superoxide anions (O2∙−). We addressed here the effects that superoxide removal has on the redox state of Cu(I) and GSH present in such complex and assessed the formation of Cu(II)-GSSG as a final oxidation product. In addition, we investigated the potential of a source of O2∙− external to the Cu(I)-[GSH]2 complex to prevent its oxidation. Removal of O2∙− from a Cu(I)-[GSH]2-containing solution, whether spontaneous or Tempol-induced, led to time-dependent losses in GSH that were greater than those affecting the metal. The losses in GSH were not accompanied by increments in GSSG but were largely accounted for by the cumulative formation of Cu(II)-GSSG molecules. Notably, the redox changes in Cu(I) and GSH were totally prevented when Cu(I)-[GSH]2 was coincubated with hypoxanthine/xanthine oxidase. Data suggest that the generation of O2∙− by Cu(I)-[GSH]2 implies the obliged formation of an intermediate whose subsequent oxidation into Cu(II)-GSSG or back reduction into Cu(I)-[GSH]2 is favoured by either the removal or the addition of O2∙−, respectively

Oxidative Damage in Lymphocytes of Copper Smelter Workers Correlated to Higher Levels of Excreted Arsenic

Arsenic has been associated with multiple harmful effects at the cellular level. Indirectly these defects could be related to impairment of the integrity of the immune system, in particular in lymphoid population. To characterize the effect of Arsenic on redox status on this population, copper smelter workers and arsenic unexposed donors were recruited for this study. We analyzed urine samples and lymphocyte enriched fractions from donors to determinate arsenic levels and lymphocyte proliferation. Moreover, we studied the presence of oxidative markers MDA, vitamin E and SOD activity in donor plasma. Here we demonstrated that in human beings exposed to high arsenic concentrations, lymphocyte MDA and arsenic urinary levels showed a positive correlation with SOD activity, and a negative correlation with vitamin E serum levels. Strikingly, lymphocytes from the arsenic exposed population respond to a polyclonal stimulator, phytohemaglutinin, with higher rates of thymidine incorporation than lymphocytes of a control population. As well, similar in vitro responses to arsenic were observed using a T cell line. Our results suggest that chronic human exposure to arsenic induces oxidative damage in lymphocytes and could be considered more relevant than evaluation of T cell surveillance

5to. Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad. Memoria académica

El V Congreso Internacional de Ciencia, Tecnología e Innovación para la Sociedad, CITIS 2019, realizado del 6 al 8 de febrero de 2019 y organizado por la Universidad Politécnica Salesiana, ofreció a la comunidad académica nacional e internacional una plataforma de comunicación unificada, dirigida a cubrir los problemas teóricos y prácticos de mayor impacto en la sociedad moderna desde la ingeniería. En esta edición, dedicada a los 25 años de vida de la UPS, los ejes temáticos estuvieron relacionados con la aplicación de la ciencia, el desarrollo tecnológico y la innovación en cinco pilares fundamentales de nuestra sociedad: la industria, la movilidad, la sostenibilidad ambiental, la información y las telecomunicaciones. El comité científico estuvo conformado formado por 48 investigadores procedentes de diez países: España, Reino Unido, Italia, Bélgica, México, Venezuela, Colombia, Brasil, Estados Unidos y Ecuador. Fueron recibidas un centenar de contribuciones, de las cuales 39 fueron aprobadas en forma de ponencias y 15 en formato poster. Estas contribuciones fueron presentadas de forma oral ante toda la comunidad académica que se dio cita en el Congreso, quienes desde el aula magna, el auditorio y la sala de usos múltiples de la Universidad Politécnica Salesiana, cumplieron respetuosamente la responsabilidad de representar a toda la sociedad en la revisión, aceptación y validación del conocimiento nuevo que fue presentado en cada exposición por los investigadores. Paralelo a las sesiones técnicas, el Congreso contó con espacios de presentación de posters científicos y cinco workshops en temáticas de vanguardia que cautivaron la atención de nuestros docentes y estudiantes. También en el marco del evento se impartieron un total de ocho conferencias magistrales en temas tan actuales como la gestión del conocimiento en la universidad-ecosistema, los retos y oportunidades de la industria 4.0, los avances de la investigación básica y aplicada en mecatrónica para el estudio de robots de nueva generación, la optimización en ingeniería con técnicas multi-objetivo, el desarrollo de las redes avanzadas en Latinoamérica y los mundos, la contaminación del aire debido al tránsito vehicular, el radón y los riesgos que representa este gas radiactivo para la salud humana, entre otros

Inhibition of mitochondrial complex i by various non-steroidal anti-inflammatory drugs and its protection by quercetin via a coenzyme Q-like action

Mitochondrial dysfunction plays a major role in the development of oxidative stress and cytotoxicity induced by non-steroidal anti-inflammatory drugs (NSAIDs). A major objective of the present study was to investigate whether in vitro the NSAIDs, aspirin, indomethacin, diclofenac, piroxicam and ibuprofen, which feature different chemical structures, are able to inhibit mitochondrial complex I. All NSAIDs were effective inhibitors when added both, directly to mitochondria isolated from rat duodenum epithelium (50 μM) or to Caco-2 cells (250 μM). In the former system, complex I inhibition was concentration-dependent and susceptible to competition and reversion by the addition of coenzyme Q (32.5-520 μM). Based on reports suggesting a potential gastro-protective activity of quercetin, the ability of this flavonoid to protect isolated mitochondria against NSAIDs-induced complex I inhibition was evaluated. Low micromolar concentrations of quercetin (1-20 μM) protected against such inhibiti

Novel benzoate-lipophilic cations selectively induce cell death in human colorectal cancer cell lines

Introduction: Colorectal cancer (CRC) is a critical health issue worldwide. The high rate of liver and lung metastasis associated with CRC creates a significant barrier to effective and efficient therapy. Tumour cells, including CRC cells, have metabolic alterations, such as high levels of glycolytic activity, increased cell proliferation and invasiveness, and chemo- and radio-resistance. However, the abnormally elevated mitochondrial transmembrane potential of these cells also provides an opportunity to develop drugs that selectively target the mitochondrial functions of tumour cells. Methods: In this work, we used a new batch of benzoic acid esters with cytotoxic activities attached to the triphenylphosphonium group as a vehicle to target tumour mitochondria and improve their activity. We evaluated the cytotoxicity, selectivity, and mechanism of action of these derivatives, including the effects on energy stress-induced apoptosis and metabolic behaviour in the human CRC cell lines HCT-15 and COLO-205. Results: The benzoic acid derivatives selectively targeted the tumour cells with high potency and efficacy. The derivatives induced the uncoupling of the oxidative phosphorylation system, decreased the transmembrane potential, and reduced ATP levels while increasing AMPK activation, thereby triggering tumour cell apoptosis in both tumour cell lines tested. Conclusion: The benzoic acid derivatives studied here are promising candidates for assessing in vivo models of CRC, despite the diverse metabolic characteristics of these tumour cells.Consejo Nacional de Ciencia y Tecnologia (CONACyT) Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) FONDECYT 11160281 FONDECYT 1180296 FONDECYT 1130189 Academy Insertion Grant 791220004 Vicerrectoría de Investigación y Desarrollo, Universidad de Chile (Enlace) ENL022/16 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) FONDECYT 11160281 Comisión Nacional de Investigación Cientifica y Tecnológica (CONICYT) CONICYT FONDECYT 1180296 1130189 Universidad de Chile (Enlace) ENL022/1

Derivatives of alkyl gallate triphenylphosphonium exhibit antitumor activity in a syngeneic murine model of mammary adenocarcinoma

We previously demonstrated that alkyl gallates coupled to triphenylphosphine have a selective and efficient antiproliferative effect by inducing mitochondria] uncoupling in vitro due to the increased mitochondrial trans membrane potential of tumor cells. Therefore, in this work, the in vivo antitumor activities of alkyl gallate triphenylphosphonium derivatives (TPP+ C-8, TPP+C10 and TPP+ C-12) were evaluated in a syngeneic murine model of breast cancer. We found that TPP+ C-10 increased the cytosolic ADP/ATP ratio and significantly increased the AMP levels in a concentration-dependent manner in TA3/Ha murine mammary adenocarcinoma cells. Interestingly, TPP+ C-10 induced a decrease in the levels of cellular proliferation markers and promoted caspase-3 activation in tumor-bearing mice. Additionally, TPP+ C-10 inhibited tumor growth in the syngeneic mouse model. Importantly, 30 days of intraperitoneal (i.p.) administration of the combination of TPP+ C-10 (10 mg/kg/48 h) and the antibiotic doxycycline (10 mg/kg/24 h) completely eliminated the subcutaneous tumor burden in mice (n = 6), without any relapses at 60 days post-treatment. This enhancement of the individual activities of TPP+C10 and doxycycline is due to the uncoupling of oxidative phosphorylation by TPP+ C-10 and the inhibition of mitochondrial biogenesis by doxycycline, as demonstrated by loss of mitochondrial mass and overexpression of PGC1-ct as an adaptive response. Moreover, i.p. administration of TPP+ C-10 (10 mg/kg/24 h) to healthy mice did not produce toxicity or damage in organs important for drug metabolism and excretion, as indicated by hematological, biochemical and histological assessments. These findings suggest that the combination of TPP+ C-10 with doxycycline is a valuable candidate therapy for breast cancer management. (C) 2017 Elsevier Inc. All rights reserved.FONDECYT 1130772 VID ENL022/16 ERANET-LAC ELAC2014/HID328 CONICYT Ph.D. fellowshi

Complex mitochondrial dysfunction induced by TPP+-gentisic acid and mitochondrial translation inhibition by doxycycline evokes synergistic lethality in breast cancer cells

The mitochondrion has emerged as a promising therapeutic target for novel cancer treatments because of its essential role in tumorigenesis and resistance to chemotherapy. Previously, we described a natural compound, 10-((2,5-dihydroxybenzoyl)oxy)decyl) triphenylphosphonium bromide (GA-TPP+C10), with a hydroquinone scaffold that selectively targets the mitochondria of breast cancer (BC) cells by binding to the triphenylphosphonium group as a chemical chaperone; however, the mechanism of action remains unclear. In this work, we showed that GA-TPP+C10 causes time-dependent complex inhibition of the mitochondrial bioenergetics of BC cells, characterized by (1) an initial phase of mitochondrial uptake with an uncoupling effect of oxidative phosphorylation, as previously reported, (2) inhibition of Complex I-dependent respiration, and (3) a late phase of mitochondrial accumulation with inhibition of alpha-ketoglutarate dehydrogenase complex (alpha KGDHC) activity. These events led to cell cycle arrest in the G1 phase and cell death at 24 and 48 h of exposure, and the cells were rescued by the addition of the cell-penetrating metabolic intermediates l-aspartic acid beta-methyl ester (mAsp) and dimethyl alpha-ketoglutarate (dm-KG). In addition, this unexpected blocking of mitochondrial function triggered metabolic remodeling toward glycolysis, AMPK activation, increased expression of proliferator-activated receptor gamma coactivator 1-alpha (pgc1 alpha) and electron transport chain (ETC) component-related genes encoded by mitochondrial DNA and downregulation of the uncoupling proteins ucp3 and ucp4, suggesting an AMPK-dependent prosurvival adaptive response in cancer cells. Consistent with this finding, we showed that inhibition of mitochondrial translation with doxycycline, a broad-spectrum antibiotic that inhibits the 28 S subunit of the mitochondrial ribosome, in the presence of GA-TPP+C10 significantly reduces the mt-CO1 and VDAC protein levels and the FCCP-stimulated maximal electron flux and promotes selective and synergistic cytotoxic effects on BC cells at 24 h of treatment. Based on our results, we propose that this combined strategy based on blockage of the adaptive response induced by mitochondrial bioenergetic inhibition may have therapeutic relevance in BC.Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT), CONICYT FONDECYT: 1180296, 21150774, 3170813

Carta de Psicología No. 56

Entre los mecanismos de divulgación de la investigación de la Facultad de Psicología se cuenta con la publicación semestral de Carta de Psicología, espacio en el cual se publican artículos cortos resultado de investigaciones desarrolladas en los diferentes escenarios de formación, para visibilizar los productos derivados de los semilleros innovo, de investigación o grupos de estudio; al igual que aquellos derivados de la interacción académica con instituciones de orden nacional e internacional, los derivados de ejercicios de investigación en el aula de clase y de actividades de extensión. Esta publicación parte de un doble reconocimiento: en su comienzo, los artículos científicos fueron epístolas de las comunidades científicas, grupos cercanos de interlocución franca y abierta. En su avance, Carta de Psicología propende por la reflexión y el diálogo a partir del reconocimiento de las experiencias valiosas que construyen universidad y diversidad en la formación, los ejercicios de investigación del aula, los avances de los proyectos de semilleros de investigación, los avances de maestría y doctorado, las voces de los egresados, entre otros, de tal manera que sirva como referencia de lo que hacemos y de lo que somos. Esta filosofía orienta el último desarrollo de la política editorial de Carta de Psicología en cuatro secciones: Investigación formativa, Interacción académica, Investigación de aula y Extensión.Investigación, integración curricular y divulgación como ejes para el cumplimiento de las funciones sustantivas en la Facultad de Psicología. El cambio de la comunicación en las relaciones afectivosexuales debido al uso de las redes sociales. Consumo de sustancias psicoactivas: una problemática juvenil. Flexibilidad cognitiva en el deterioro cognitivo leve. Relación entre clima organizacional y engagement en empleados de Bogotá. Relación entre el estrés y el desempeño laboral: revisión teórica. Percepción del liderazgo transformacional con relación a las variables sociodemográficas de la población colombiana. Programas de Outplacement para trabajadores en relación con su calidad de vida. Violencia sexual y redes sociales. Los juegos en redes y la violencia autoinfligida. El sentido de comunidad y la crisis económica, social y política en Colombia. Consumo de alcohol de estudiantes universitarios antes y durante la pandemia COVID-19. Resultados preliminares. Uso de la tecnología para la aplicación del instrumento para valorar la comprensión de síntesis. Consecuencias de los modelos de pautas de crianza en el desarrollo infantil. La justicia más allá de la equidad: un breve comentario del libro Las fronteras de la justicia, de Martha Nussbaum. Conceptualización y consecuencias del maltrato Infantil Exploración de factores de riesgo y los efectosdel reclutamiento forzado en el desarrollo infantil. Indicadores de aprendizaje para la educación integral de la sexualidad. Instrumento de medición de afectividad y erotismo en trabajadoras sexuales de Bogotá. Toma de decisiones y vida sexual: autocuidado, relaciones afectivas y toma de decisiones en niños/niñas. Convicciones y conductas sobre virginidad. Significado y valor de acuerdo con las diferencias generacionales. Percepción sobre el concepto, situación y vulneración de los derechos humanos en el departamento de Santander, Colombia. Factores que influyen en la vulnerabilidad frente al delito de la trata de personas en estudiantes universitarios de la Universidad Cooperativa de Colombia. Violencia intrafamiliar desde la perspectiva del agresor: un estudio de caso en la cárcel de máxima seguridad de Palogordo de Bucaramanga