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1.
Acta Cir Bras ; 35(3): e202000301, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32401830

RESUMEN

PURPOSE: To analyze the serum levels of nitric oxide and correlate them with the levels of thiobarbituric acid reactive substances (TBARS) in liver, brain and spinal cord of animals using L-NAME and treated with hydroxyurea. METHODS: Eighteen male albino Wistar rats were divided into three groups. NG-nitro-L-arginine methyl ester (L-NAME) was intraperitoneally administered to induce oxidative stress. TBARS and plasma nitric oxide levels were analyzed in all groups. Histopathology of the liver and vascular tissue was performed. RESULTS: Statistically significant differences were seen in liver, brain and spinal cord TBARS levels. CONCLUSIONS: Following the use of L-NAME, hepatic tissue increased the number of Kupffer cells as oxidative stress and inflammatory response increased. The use of L-NAME caused an increase in lipid peroxidation products and, consequently, in oxidative stress in animals. Hydroxyurea doses of 35 mg / kg / day reduced TBARS values in liver, brain and spinal cord.


Asunto(s)
Anemia de Células Falciformes/tratamiento farmacológico , Encéfalo/metabolismo , Hidroxiurea/uso terapéutico , Hígado/metabolismo , Estrés Oxidativo/fisiología , Médula Espinal/metabolismo , Anemia de Células Falciformes/metabolismo , Anemia de Células Falciformes/fisiopatología , Animales , Modelos Animales de Enfermedad , Masculino , NG-Nitroarginina Metil Éster , Ratas , Ratas Wistar
2.
Chemosphere ; 250: 126416, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-32380589

RESUMEN

The flavonoid metal-insecticide magnesium-hesperidin complex (MgHP) has recently been considered as a novel insecticide to replace some persistent pesticides. However, it is important to evaluate its action on non-target species, mainly those living in an aquatic environment, as these ecosystems are the final receptors of most chemicals. Reactive oxygen species, antioxidant and oxidative stress biomarkers, genotoxicity as well as cell cycle was evaluated in the liver cell line from zebrafish (Danio rerio; ZF-L) exposed to 0, 0.1, 1, 10, 100 and 1000 ng mL-1 MgHP. MgHP affected cell stability by increasing reactive oxygen species (ROS) in both exposure times (24 and 96 h) at high concentrations. Catalase (CAT) activity decreased after 24 h exposure, and glutathione and metallothionein values increased, avoiding the lipid peroxidation. Genotoxicity increased as MgHP concentration increased, after 24 h exposure, exhibiting nuclear abnormalities; it was recovered after 96 h exposure, evidencing possible stimulation of DNA repair mechanisms. The alteration in the cell cycle (increasing in the Sub-G1 phase and decreasing in the S-phase) was associated with chromosomal instability. In conclusion, the responses of ROS and the antioxidant defense system depended on MgHP concentration and time exposure, while DNA exhibited some instability after 24 h exposure, which was recovered after 96 h.


Asunto(s)
Ciclo Celular/efectos de los fármacos , Insecticidas/toxicidad , Hígado/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Animales , Antioxidantes/metabolismo , Línea Celular , Daño del ADN , Relación Dosis-Respuesta a Droga , Ecotoxicología/métodos , Biomarcadores Ambientales/efectos de los fármacos , Glutatión/metabolismo , Hesperidina/química , Hesperidina/toxicidad , Insecticidas/administración & dosificación , Insecticidas/química , Peroxidación de Lípido/efectos de los fármacos , Hígado/citología , Hígado/metabolismo , Magnesio/química , Pruebas de Mutagenicidad/métodos , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Contaminantes Químicos del Agua/química , Pez Cebra
3.
Chem Biol Interact ; 324: 109086, 2020 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-32275923

RESUMEN

Oxidative stress-induced apoptosis of retinal ganglion cells (RGCs) contributes to the development and progression of glaucoma. Sestrin2 (Sesn2), a stress-inducible protein, has a potent antioxidant capacity that can provide cytoprotection against various noxious stimuli. However, whether Sesn2 is involved in protecting RGCs from oxidative stress remains unexplored. The purpose of this study was to evaluate the role of Sesn2 in regulating hydrogen peroxide (H2O2)-induced oxidative stress of RGCs. Here, we showed that Sesn2 expression was induced in RGCs following H2O2 exposure. Sesn2 depletion markedly exacerbated H2O2-induced apoptosis and reactive oxygen species (ROS) generation in RGCs. Notably, upregulation of Sesn2 significantly decreased H2O2-induced apoptosis and ROS generation. Moreover, Sesn2 overexpression increased the nuclear translocation of nuclear factor erythroid-derived 2-like 2 (Nrf2), elevated Nrf2/antioxidant response element (ARE)-mediated transcriptional activity and upregulated the expression of Nrf2 target genes in H2O2-stimulated RGCs. Interestingly, we found that Sesn2 promoted Nrf2/ARE activation through downregulation of kelch-like ECH-associated protein 1 (Keap1). Restoration of Keap1 or inhibition of Nrf2 significantly reversed the Sesn2-mediated protective effect in H2O2-stimulated RGCs. In conclusion, these results elucidated that Sesn2 confers a protective effect in RGCs against H2O2-induced oxidative stress by reinforcing Nrf2/ARE activation via downregulation of Keap1. Our study suggests that the Sesn2/Keap1/Nrf2 axis may play an important role in retinal degeneration in glaucoma.


Asunto(s)
Apoptosis/fisiología , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Proteínas Nucleares/metabolismo , Estrés Oxidativo/fisiología , Células Ganglionares de la Retina/metabolismo , Animales , Elementos de Respuesta Antioxidante/fisiología , Apoptosis/efectos de los fármacos , Regulación hacia Abajo , Peróxido de Hidrógeno/farmacología , Estrés Oxidativo/efectos de los fármacos , Ratas , Células Ganglionares de la Retina/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación hacia Arriba
4.
Braz J Med Biol Res ; 53(4): e8770, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32294698

RESUMEN

Early mobilization is beneficial for critically ill patients because it reduces muscle weakness acquired in intensive care units. The objective of this study was to assess the effect of functional electrical stimulation (FES) and passive cycle ergometry (PCE) on the nitrous stress and inflammatory cytometry in critically ill patients. This was a controlled, randomized, open clinical trial carried out in a 16-bed intensive care unit. The patients were randomized into four groups: Control group (n=10), did not undergo any therapeutic intervention during the study; PCE group (n=9), lower-limb PCE for 30 cycles/min for 20 min; FES group (n=9), electrical stimulation of quadriceps muscle for 20 min; and FES with PCE group (n=7), patients underwent PCE and FES, with their order determined randomly. The serum levels of nitric oxide, tumor necrosis factor alpha, interferon gamma, and interleukins 6 and 10 were analyzed before and after the intervention. There were no differences in clinical or demographic characteristics between the groups. The results revealed reduced nitric oxide concentrations one hour after using PCE (P<0.001) and FES (P<0.05), thereby indicating that these therapies may reduce cellular nitrosative stress when applied separately. Tumor necrosis factor alpha levels were reduced after the PCE intervention (P=0.049). PCE and FES reduced nitric oxide levels, demonstrating beneficial effects on the reduction of nitrosative stress. PCE was the only treatment that reduced the tumor necrosis factor alpha concentration.


Asunto(s)
Enfermedad Crítica/terapia , Citocinas/sangre , Terapia Pasiva Continua de Movimiento/métodos , Estrés Nitrosativo/fisiología , Respiración Artificial/métodos , Adulto , Anciano , Biomarcadores/sangre , Enfermedad Crítica/rehabilitación , Estimulación Eléctrica/métodos , Femenino , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Músculo Cuádriceps/fisiopatología
5.
Einstein (Sao Paulo) ; 18: eAO5075, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-32321080

RESUMEN

OBJECTIVE: To evaluate the nutritional risk factors in patients eligible for hematopoietic stem cell transplantation. METHODS: A cross-sectional, descriptive study conducted with patients recruited from an hematology outpatient clinic. Study variables included demographic and clinical data, patient-generated global subjective assessment findings, anthropometric indicators, food intake and oxidative stress levels. The level of significance was set at 5% (p<0.05). RESULTS: The sample comprised 72 patients, mean age of 48.93 years (14.5%). Multiple myeloma was the most prevalent condition (51.4%) in this sample. Most patients (55.6%) were overweight according to body mass index and at risk of cardiovascular disease according to waist circumference, conicity index and percentage of body fat. Sarcopenia was associated with risk of cardiovascular disease, hip-to-waist ratio (p=0.021), muscle strength depletion (p<0.001), food intake (p=0.023), reduced functional capacity (p=0.048), self-reported well-nourished status; p=0.044) and inadequate vitamin B6 (p=0.022) and manganese (p=0.026) intake. Elevated oxidative stress, detected in 33.3% of patients in this sample, was not associated with sarcopenia. CONCLUSION: Most patients in this sample were overweight and sarcopenic. Lean mass depletion was associated with risk of cardiovascular disease, reduced muscle strength, food intake changes, reduced functional capacity, self-reported well-nourished status and inadequate intake of vitamin B6 and manganese, but not with oxidative stress.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas/efectos adversos , Evaluación Nutricional , Medición de Riesgo/métodos , Adulto , Antropometría , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/fisiopatología , Estudios Transversales , Ingestión de Alimentos/fisiología , Ingestión de Energía/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mieloma Múltiple/fisiopatología , Mieloma Múltiple/cirugía , Fuerza Muscular/fisiología , Estado Nutricional/fisiología , Sobrepeso/complicaciones , Sobrepeso/fisiopatología , Estrés Oxidativo/fisiología , Factores de Riesgo , Sarcopenia/complicaciones , Sarcopenia/fisiopatología
6.
Einstein (Sao Paulo) ; 18: eAO5022, 2020.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-32215468

RESUMEN

OBJECTIVE: To evaluate the effects of oxidative stress on insulin signaling in cardiac tissue of obese mice. METHODS: Thirty Swiss mice were equally divided (n=10) into three groups: Control Group, Obese Group, and Obese Group Treated with N-acetylcysteine. After obesity and insulin resistance were established, the obese mice were treated with N-acetylcysteine at a dose of 50mg/kg daily for 15 days via oral gavage. RESULTS: Higher blood glucose levels and nitrite and carbonyl contents, and lower protein levels of glutathione peroxidase and phosphorylated protein kinase B were observed in the obese group when compared with their respective control. On the other hand, treatment with N-acetylcysteine was effective in reducing blood glucose levels and nitrite and carbonyl contents, and significantly increased protein levels of glutathione peroxidase and phosphorylated protein kinase B compared to the Obese Group. CONCLUSION: Obesity and/or a high-lipid diet may result in oxidative stress and insulin resistance in the heart tissue of obese mice, and the use of N-acetylcysteine as a methodological and therapeutic strategy suggested there is a relation between them.


Asunto(s)
Acetilcisteína/farmacología , Dieta Alta en Grasa , Depuradores de Radicales Libres/farmacología , Resistencia a la Insulina/fisiología , Miocardio/metabolismo , Obesidad/metabolismo , Estrés Oxidativo/fisiología , Animales , Glucemia/análisis , Western Blotting , Peso Corporal , Fluoresceínas/análisis , Humanos , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Carbonilación Proteica , Especies Reactivas de Oxígeno/análisis , Valores de Referencia , Espectrofotometría
7.
Invest Ophthalmol Vis Sci ; 61(2): 4, 2020 02 07.
Artículo en Inglés | MEDLINE | ID: mdl-32031576

RESUMEN

Purpose: Oxidative stress affects the retinal pigment epithelium (RPE) leading to development of vascular eye diseases. Cholecalciferol (VIT-D) is a known modulator of oxidative stress and angiogenesis. This in vitro study was carried out to evaluate the protective role of VIT-D on RPE cells incubated under hyperoxic conditions. Methods: Cadaver primary RPE (PRPE) cells were cultured in hyperoxia (40% O2) with or without VIT-D (α-1, 25(OH) 2D3). The functional and physiological effects of PRPE cells with VIT-D treatment were analyzed using molecular and biochemical tools. Results: Vascular signaling modulators, such as vascular endothelial growth factor (VEGF) and Notch, were reduced in hyperoxic conditions but significantly upregulated in the presence of VIT-D. Additionally, PRPE conditioned medium with VIT-D induced the tubulogenesis in primary human umbilical vein endothelial cells (HUVEC) cells. VIT-D supplementation restored phagocytosis and transmembrane potential in PRPE cells cultured under hyperoxia. Conclusions: VIT-D protects RPE cells and promotes angiogenesis under hyperoxic insult. These findings may give impetus to the potential of VIT-D as a therapeutic agent in hyperoxia induced retinal vascular diseases.


Asunto(s)
Colecalciferol/farmacología , Hiperoxia/fisiopatología , Epitelio Pigmentado de la Retina/efectos de los fármacos , Vitaminas/farmacología , Adolescente , Adulto , Cadáver , Células Cultivadas , Niño , Preescolar , Células Endoteliales de la Vena Umbilical Humana , Humanos , Potenciales de la Membrana/fisiología , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Fagocitosis/efectos de los fármacos , Fagocitosis/fisiología , Receptores Notch/metabolismo , Regulación hacia Arriba/fisiología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Adulto Joven
8.
Chemosphere ; 248: 125941, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32004883

RESUMEN

Thiophanate-methyl (TM) is widely used all over the world and is a typical example of pesticide residues, which can be detected in the soil, and even in vegetables and fruits. However, the molecular mechanisms underlying the hepatotoxicity of TM are not well understood. In this study, we utilized zebrafish to comprehensively evaluate the hepatotoxicity of TM and explore how the molecular mechanisms of hepatotoxicity are induced. The zebrafish larvae were exposed in 6.25, 12.5 and 25 mg/L TM from 72 to 144 hpf, while the adults were exposed in 2, 4 and 6 mg/L TM for 28 days. Here, we found that 12.5 and 25 mg/L TM induces specifically serious hepatotoxicity but not the toxicity of other organs in zebrafish larvae and adults. Moreover, it might triggered hepatotoxicity by activating the caspase-3 through apoptotic pathways and oxidative stress in zebrafish. Subsequently, this resulted in a metabolic imbalance in the zebrafish's liver. In conclusion, our results disclosed the fact that TM may induce severe hepatotoxicity by mediating activation of caspase-3 and oxidative stress in zebrafish.


Asunto(s)
Hígado/efectos de los fármacos , Tiofanato/toxicidad , Contaminantes Químicos del Agua/toxicidad , Animales , Caspasa 3 , Enfermedad Hepática Inducida por Sustancias y Drogas , Larva , Estrés Oxidativo/fisiología , Residuos de Plaguicidas/metabolismo , Pez Cebra/metabolismo , Pez Cebra/fisiología
9.
Nutr. hosp ; 37(1): 6-13, ene.-feb. 2020. tab, graf
Artículo en Inglés | IBECS | ID: ibc-187568

RESUMEN

Background: systemic inflammation and oxidative stress are important factors in the pathogenesis of bronchiectasis. Pulmonary rehabilitation (PR) is recommended for bronchiectasis, but there is no data about its effect on the inflammatory and REDOX status of these patients. Aims: to investigate the effect of PR in non-cystic-fibrosis bronchiectasis (NCFB) patients, and to compare it with the effect of PR plus a hyperproteic oral nutritional supplement (PRS) enriched with beta-hydroxy-beta-methylbutyrate (HMB) on serum inflammatory and oxidative biomarkers. Materials and methods: this was an open randomized, controlled trial. Thirty individuals (65 years old or younger with a body mass index over 18.5, older than 65 years with a body mass index over 20) were recruited from September 2013 to September 2014, and randomly assigned to receive PR or PRS. Total neutrophils, and inflammatory and oxidative biomarker levels were measured at baseline, and then at 3 and 6 months. Results: in the PRS group neutrophil levels were decreased from baseline at 6 months. A significantly different fold change was found between the PR and PRS groups. In the PR group, IL-6 and adiponectin were increased by the end of the study while TNFa levels were decreased from baseline at 6 months. REDOX biomarkers remained stable throughout the study except for 8-isoprostane levels, which were increased from baseline at 6 months in both groups of patients. Conclusion: a PR program induced a pro-oxidative effect accompanied by changes in circulating inflammatory cytokine levels in NCFB patients. Our results would also suggest a possible beneficial effect of the HMB enriched supplement on neutrophil level regulation in these patients. The information provided in this study could be useful for choosing the right therapeutic approach in the management of bronchiectasis


Introducción: la inflamación sistémica y el estrés oxidativo son factores importantes en la patogénesis de la bronquiectasia. La rehabilitación pulmonar (PR) está recomendada en los sujetos con bronquiectasias, pero no hay datos sobre sus posibles efectos sobre el estado inflamatorio y REDOX de estos pacientes. Objetivos: investigar el efecto de la PR en pacientes con bronquiectasias no asociadas a fibrosis quística (NCFB) sobre los biomarcadores oxidativos e inflamatorios, y compararlo con los efectos de la PR junto con la suplementación oral de un suplemento hiperproteico (PRS) enriquecido con beta-hidroxi-beta-metilbutirato (HMB). Material y métodos: ensayo clínico abierto, aleatorizado y controlado. Treinta pacientes (de 65 años o menos con un índice de masa corporal por encima de 18,5, y mayores de 65 años con un índice de masa corporal de más de 20) se aleatorizaron para recibir PR o PRS. Los niveles circulantes de neutrófilos totales y los de biomarcadores de estado inflamatorio y oxidativo se determinaron al inicio del estudio y a los 3 y 6 meses. Resultados: los niveles de neutrófilos en el grupo de PRS se redujeron desde el inicio a los 6 meses, presentando una tasa de cambio significativamente diferente según el tratamiento. En el grupo de PR, la IL-6 y la adiponectina aumentaron al final del estudio, mientras que los niveles de TNFa disminuyeron desde el inicio a los 6 meses. Los biomarcadores de estrés oxidativo se mantuvieron estables durante todo el estudio excepto por los niveles de 8-isoprostano, que aumentaron desde el inicio a los 6 meses en ambos grupos de pacientes. Conclusión: el programa de PR indujo un efecto pro-oxidativo acompañado de cambios en los niveles de citoquinas inflamatorias circulantes en pacientes con NCFB. Nuestros resultados también sugieren un posible efecto beneficioso del suplemento nutricional sobre la regulación de los niveles de neutrófilos de estos pacientes


Asunto(s)
Humanos , Masculino , Adulto , Persona de Mediana Edad , Bronquiectasia/rehabilitación , Estrés Oxidativo/fisiología , Neutrófilos/metabolismo , Suplementos Dietéticos , Nutrientes/administración & dosificación , Estudios Prospectivos , Índice de Masa Corporal
10.
Int J Sports Med ; 41(5): 339-344, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32045948

RESUMEN

Aging is associated with increased oxidative stress, chronic inflammation, and decreased telomere length (TL). However, the lifestyle of master athletes can lead to a reduced risk of these conditions, and thus attenuates aging and performance deterioration. We aimed to analyze the relationships between TL and relative performance (RP), and their relation to adiposity, oxidative stress, and inflammation in endurance (END) and sprint/power (SPW) master athletes (MAs). Twenty-two world-class MAs visited the laboratory for anamnesis, anthropometrics, and blood sampling. Inflammatory and oxidative stress parameters were assessed using commercial kits. Relative TL was determined in leukocytes through qPCR analyses. A positive association was observed between RP and TL in both groups (SPW: r=0.641; END: r=0.685) and the whole sample (r=0.594). The IL6/IL10 ratio presented an inverse correlation with RP in the whole sample (r=-0.580). Body mass index also demonstrated a negative correlation with TL for the END group (r=-0.690) and the whole sample analysis (r=-0.455). Moreover, the IL6/IL10 ratio was negatively associated with strength/power training hours (r=-0.464), whereas the CAT/TBARS ratio was negatively associated with aerobic training hours (r=-0.482). In conclusion, TL of MAs was associated with RP regardless of the training model (endurance or sprint/power), and inflammation and adiposity were associated with shorter telomeres.


Asunto(s)
Envejecimiento/fisiología , Rendimiento Atlético/fisiología , Estilo de Vida Saludable , Acortamiento del Telómero/fisiología , Adiposidad/fisiología , Adulto , Anciano , Humanos , Inflamación/fisiopatología , Masculino , Persona de Mediana Edad , Estrés Oxidativo/fisiología , Acondicionamiento Físico Humano/métodos , Resistencia Física/fisiología
11.
PLoS One ; 15(2): e0229332, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32092105

RESUMEN

The placenta, a tissue that is metabolically active and rich in mitochondria, forms a critical interface between the mother and developing fetus. Oxidative stress within this tissue, derived from the dysregulation of reactive oxygen species (ROS), has been linked to a number of adverse fetal outcomes. While such outcomes have been associated with mitochondrial dysfunction, the causal role of mitochondrial dysfunction and mitochondrially generated ROS in altering the process of placentation remains unclear. In this study, mitochondrial complex I activity was attenuated using 10 nM rotenone to induce cellular oxidative stress by increasing mitochondrial ROS production in the BeWo choriocarcinoma cell line. Increased mitochondrial ROS resulted in a significant decrease in the transcripts which encode for proteins associated with fusion (GCM1, ERVW-1, and ERVFRD-1) resulting in a 5-fold decrease in the percentage of BeWo fusion. This outcome was associated with increased indicators of mitochondrial fragmentation, as determined by decreased expression of MFN2 and OPA1 along with an increase in a marker of mitochondrial fission (DRP1). Importantly, increased mitochondrial ROS also resulted in a 5.0-fold reduction of human placental lactogen (PL) and a 4.4-fold reduction of insulin like growth factor 2 (IGF2) transcripts; hormones which play an important role in regulating fetal growth. The pre-treatment of rotenone-exposed cells with 5 mM N-acetyl cysteine (NAC) resulted in the prevention of these ROS mediated changes in BeWo function and supports a central role for mitochondrial ROS signaling in the maintenance and function of the materno-fetal interface.


Asunto(s)
Mitocondrias/metabolismo , Hormonas Placentarias/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Trofoblastos/metabolismo , Fusión Celular , Células Cultivadas , Femenino , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/fisiología , Estrés Oxidativo/efectos de los fármacos , Estrés Oxidativo/fisiología , Embarazo , Especies Reactivas de Oxígeno/farmacología , Rotenona/farmacología , Transducción de Señal/efectos de los fármacos , Trofoblastos/efectos de los fármacos
12.
PLoS One ; 15(2): e0229103, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32053677

RESUMEN

Chemical modifications that regulate protein expression at the translational level are emerging as vital components of the cellular stress response. Transfer RNAs (tRNAs) are significant targets for methyl-based modifications, which are catalyzed by tRNA methyltransferases (Trms). Here, Saccharomyces cerevisiae served as a model eukaryote system to investigate the role of 2'-O-ribose tRNA methylation in the cell's response to oxidative stress. Using 2'-O-ribose deletion mutants for trms 3, 7, 13, and 44, in acute and chronic exposure settings, we demonstrate a broad cell sensitivity to oxidative stress-inducing toxicants (i.e., hydrogen peroxide, rotenone, and acetic acid). A global analysis of hydrogen peroxide-induced tRNA modifications shows a complex profile of decreased, or undetectable, 2'-O-ribose modification events in 2'-O-ribose trm mutant strains, providing a critical link between this type of modification event and Trm status post-exposure. Based on the pronounced oxidative stress sensitivity observed for trm7 mutants, we used a bioinformatic tool to identify transcripts as candidates for regulation by Trm7-catalyzed modifications (i.e., enriched in UUC codons decoded by tRNAPheGmAA). This screen identified transcripts linked to diverse biological processes that promote cellular recovery after oxidative stress exposure, including DNA repair, chromatin remodeling, and nutrient acquisition (i.e., CRT10, HIR3, HXT2, and GNP1); moreover, these mutants were also oxidative stress-sensitive. Together, these results solidify a role for TRM3, 7, 13, and 44, in the cellular response to oxidative stress, and implicate 2'-O-ribose tRNA modification as an epitranscriptomic strategy for oxidative stress recovery.


Asunto(s)
ARN de Transferencia/metabolismo , Ribosa/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Ensamble y Desensamble de Cromatina/genética , Ensamble y Desensamble de Cromatina/fisiología , Reparación del ADN/genética , Estrés Oxidativo/genética , Estrés Oxidativo/fisiología , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , ARNt Metiltransferasas/genética , ARNt Metiltransferasas/metabolismo
13.
Nat Commun ; 11(1): 1050, 2020 02 26.
Artículo en Inglés | MEDLINE | ID: mdl-32103012

RESUMEN

Organisms respond to tissue damage through the upregulation of protective responses which restore tissue structure and metabolic function. Mitochondria are key sources of intracellular oxidative metabolic signals that maintain cellular homeostasis. Here we report that tissue and cellular wounding triggers rapid and reversible mitochondrial fragmentation. Elevated mitochondrial fragmentation either in fzo-1 fusion-defective mutants or after acute drug treatment accelerates actin-based wound closure. Wounding triggered mitochondrial fragmentation is independent of the GTPase DRP-1 but acts via the mitochondrial Rho GTPase MIRO-1 and cytosolic Ca2+. The fragmented mitochondria and accelerated wound closure of fzo-1 mutants are dependent on MIRO-1 function. Genetic and transcriptomic analyzes show that enhanced mitochondrial fragmentation accelerates wound closure via the upregulation of mtROS and Cytochrome P450. Our results reveal how mitochondrial dynamics respond to cellular and tissue injury and promote tissue repair.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/fisiología , Proteínas Mitocondriales/metabolismo , Cicatrización de Heridas/fisiología , Proteínas de Unión al GTP rho/metabolismo , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Calcio/metabolismo , Sistema Enzimático del Citocromo P-450/metabolismo , GTP Fosfohidrolasas/genética , Mitocondrias/metabolismo , Proteínas Mitocondriales/genética , Oxidación-Reducción , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Proteínas de Unión al GTP rho/genética
14.
Chemosphere ; 249: 126119, 2020 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-32044610

RESUMEN

The addition of different functional groups to ionic liquid anions or cations to synthesize task-specific ionic liquids (TSILs) according to specific needs has become a research hotspot. However, there are few studies on the toxicity of TSILs. We selected zebrafish (Danio rerio) to assess the toxicity of three TSILs 1-aminoethyl-3-methylimidazolium tetrafluoroborate ([C2NH2MIm]BF4), 1-methoxyethyl-3-methylimidazolium tetrafluoroborate ([MOEMIm]BF4) and 1-hydroxyethyl-3-methylimidazolium tetrafluoroborate ([HOEMIm]BF4). The 96 h median lethal concentration (96 h LC50) of the three TSILs [C2NH2MIm]BF4, [MOEMIm]BF4 and [HOEMIm]BF4 on zebrafish determined by an acute toxicity test were 143.8 mg/L, 2492.5 mg/L and 3086.7 mg/L, respectively. In the oxidative damage and DNA damage research experiments, zebrafish were exposed to [C2NH2MIm]BF4 (0, 5, 10, 20 and 40 mg/L), [MOEMIm]BF4 and [HOEMIm]BF4 (0, 1, 10, 50 and 100 mg/L) for 28 days, and levels of reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), malondialdehyde (MDA) and olive tail moment (OTM) in zebrafish liver were tested on days 7, 14, 21 and 28 after the exposure test. During the experiment, increased contents of ROS and MDA were detected; enzymatic activities especially SOD were inhibited; and DNA damage occurred in zebrafish. The toxicity of the three TSILs was compared by the integrated biomarker response (IBR). The toxicity order of three TSILs was: [MOEMIm]BF4 > [HOEMIm]BF4 > [C2NH2MIm]BF4. In addition, this study can provide a toxicological basis for application research and the evaluation of functionalized ionic liquids with low toxicity in the future.


Asunto(s)
Líquidos Iónicos/toxicidad , Pruebas de Toxicidad Aguda , Contaminantes Químicos del Agua/toxicidad , Pez Cebra/fisiología , Animales , Aniones , Boratos , Catalasa/metabolismo , Daño del ADN , Glutatión Transferasa/metabolismo , Hígado/metabolismo , Malondialdehído/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Pez Cebra/metabolismo
15.
DNA Cell Biol ; 39(4): 661-670, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32101022

RESUMEN

Fibroblast growth factor 21 (FGF21) is a hormone-like member of the FGF family that is associated with cell death in atherosclerosis. However, its underlying mechanisms remain unclear. In this study, the effect of FGF21 on endothelial cell pyroptosis and its potential mechanisms were investigated. Results showed that FGF21 inhibits oxidized low-density lipoprotein (ox-LDL)-induced pyroptosis and related molecular expression in human umbilical vein endothelial cells (HUVECs). Mitochondrial function was damaged by ox-LDL and restored by FGF21. A mechanism proved that ubiquinol cytochrome c reductase core protein I (UQCRC1) was downregulated by ox-LDL and upregulated by FGF21. Further, the silencing of UQCRC1 aggravated HUVEC pyroptosis and impaired mitochondrial function and reactive oxygen species (ROS) production. Moreover, Tet methylcytosine dioxygenase (TET2) was involved in the regulation of UQCRC1 expression and pyroptosis. In summary, FGF21 inhibited ox-LDL-induced HUVEC pyroptosis through the TET2-UQCRC1-ROS pathway.


Asunto(s)
Complejo III de Transporte de Electrones/metabolismo , Factores de Crecimiento de Fibroblastos/metabolismo , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Lipoproteínas LDL/metabolismo , Piroptosis/fisiología , Aterosclerosis/patología , Supervivencia Celular , Células Cultivadas , Proteínas de Unión al ADN/metabolismo , Complejo III de Transporte de Electrones/genética , Factores de Crecimiento de Fibroblastos/genética , Humanos , Potencial de la Membrana Mitocondrial/fisiología , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Proteínas Proto-Oncogénicas/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal
16.
Biochemistry (Mosc) ; 85(1): 40-53, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32079516

RESUMEN

The review describes molecular mechanisms for sensing oxygen levels in various compartments of animal cell. Several pathways for intracellular oxygen sensing are discussed together with details of functioning of the near-membrane and cytoplasmic pools of molecular components in hypoxic cells. The data on the role of mitochondria in cell sensitivity to a decreased oxygen content are presented. Details of mutual influence of the operational and chronic intracellular mechanisms for detecting the negative gradients of molecular oxygen concentration and their relationship with cell metabolism response to the oxidative stress are discussed.


Asunto(s)
Citoplasma/metabolismo , Hipoxia/metabolismo , Canales Iónicos/metabolismo , Mitocondrias/metabolismo , Estrés Oxidativo/fisiología , Oxígeno/metabolismo , Animales , Humanos , Ratones , Proteínas Mitocondriales/metabolismo , Ratas
17.
Chemosphere ; 246: 125661, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-31891846

RESUMEN

Neonicotinoids are increasingly being used for pest control, and their potential health risks are now receiving attention. In this study, the toxic effects of three neonicotinoids (dinotefuran, nitenpyram and acetamiprid) were evaluated in ICR mice. After 30 days of exposure to neonicotinoids (1/200 LD50), oxidative stress levels, biochemical parameters, free fatty acids contents, and 1H NMR-based hepatic metabolomics were tested. All treatment groups showed signs of amino acid metabolism disorders especially elevated branched chain amino acids and phenylalanine. Furthermore, animals exposed to neonicotinoids had elevated lipid levels, which induced oxidative stress. Overall, we found that oxidative stress is a common toxic effect of exposure to neonicotinoids. In addition, lipid accumulation induced by amino acid metabolism disorder may be the cause of oxidative stress. Our results further our understanding of the toxicological effects of neonicotinoids on mammals.


Asunto(s)
Insecticidas/toxicidad , Neonicotinoides/toxicidad , Estrés Oxidativo/fisiología , Aminoácidos/metabolismo , Animales , Guanidinas , Trastornos del Metabolismo de los Lípidos/inducido químicamente , Ratones , Ratones Endogámicos ICR , Nitrocompuestos , Pruebas de Toxicidad
18.
Life Sci ; 247: 117334, 2020 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-31962131

RESUMEN

AIMS: The role of long noncoding RNA ZEB1 antisense 1 (lncRNA ZEB1-AS1) in carotid artery atherosclerosis remains barely explored. MATERIALS AND METHODS: The viability and apoptosis of HCtAEC cells were measured by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), Caspase-3 activity detection assay and flow cytometry. The oxidative stress status and inflammation of THP-1 cells were detected by oxidative stress indicator detection kit and Enzyme-linked immunosorbent assay (ELISA). The abundance of ZEB1-AS1, miR-942 and high-mobility group box 1 (HMGB1) was measured by quantitative real time polymerase chain reaction (qRT-PCR). The targets of ZEB1-AS1 and miR-942 in HCtAEC and THP-1 cells were predicted by DIANA tool, and the combination was confirmed by dual-luciferase reporter assay, RNA immunoprecipitation (RIP) assay and RNA-pull down assay. Western blot was conducted to examine the protein expression of HMGB1. KEY FINDINGS: ZEB1-AS1 promoted ox-LDL-mediated injury in HCtAEC and THP-1 cells. MiR-942 was a direct target of ZEB1-AS1, and it was negatively modulated by ZEB1-AS1 in HCtAEC and THP-1 cells. HMGB1 could bind to miR-942, and it was regulated by ZEB1-AS1/miR-942 axis in HCtAEC and THP-1 cells. HMGB1 overexpression or miR-942 depletion reversed the inhibitory effects of ZEB1-AS1 intervention on the injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells. SIGNIFICANCE: LncRNA ZEB1-AS1 contributed to ox-LDL-mediated injury and apoptosis of HCtAEC cells and the oxidative stress and inflammation of THP-1 cells through up-regulating HMGB1 via sponging miR-942. ZEB1-AS1/miR-942/HMGB1 axis might provide a new direction to treatment carotid artery atherosclerosis.


Asunto(s)
Proteína HMGB1/metabolismo , Lipoproteínas LDL/metabolismo , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo , Apoptosis , Arterias Carótidas/metabolismo , Células Endoteliales , Regulación Neoplásica de la Expresión Génica , Humanos , Inflamación/metabolismo , MicroARNs , Estrés Oxidativo/fisiología , ARN Largo no Codificante/metabolismo , Transducción de Señal , Células THP-1
19.
Ecotoxicol Environ Saf ; 190: 110133, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31896473

RESUMEN

Microplastics (MP) are receiving increased attention as a harmful environmental pollutant, however information on the reproduction toxicity of MP in terrestrial animals, especially mammals, is limited. In this experiment, we investigated the impact of polystyrene microplastics (micro-PS) on the reproductive system of male mice. Healthy Balb/c mice were exposed to saline or to different doses of micro-PS for 6 weeks. The results showed that micro-PS exposure resulted in a significant decrease in the number and motility of sperm, and a significant increase in sperm deformity rate. We also detected a decrease in the activity of the sperm metabolism-related enzymes, succinate dehydrogenase (SDH) and lactate dehydrogenase (LDH), and a decrease in the serum testosterone content in the micro-PS exposure group. We found that micro-PS exposure caused oxidative stress and activated JNK and p38 MAPK. In addition, we found that when N-acetylcysteine (NAC) scavenges ROS, and when the p38 MAPK-specific inhibitor SB203580 inhibits p38MAPK, the micro-PS-induced sperm damage is alleviated and testosterone secretion improves. In conclusion, our findings suggest that micro-PS induces reproductive toxicity in mice through oxidative stress and activation of the p38 MAPK signaling pathways.


Asunto(s)
Microplásticos/toxicidad , Estrés Oxidativo/fisiología , Poliestirenos/toxicidad , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Acetilcisteína/farmacología , Animales , Sistema de Señalización de MAP Quinasas/fisiología , Masculino , Ratones , Plásticos , Reproducción/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Espermatozoides/metabolismo
20.
Ecotoxicology ; 29(2): 156-162, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-31927676

RESUMEN

Nanomaterials have revolutionized many scientific fields and are widely applied to address environmental problems and to develop novel health care strategies. However, their mechanism of action is still poorly understood. Several nanomaterials for medical applications are based on quantum dots (QDs). Despite their amazing physico-chemical properties, quantum dots display significant adverse effects. In the present study, the effects of QDs on the motor nervous system of nematodes Caenorhabditis elegans have been investigated as a non-mammalian alternative model. We also explored the possibility of modifying the toxicity of QDs by coating with a cell-penetrating peptide gH625 and thus we analysed the effects determined by QDs-gH625 complexes on the nematodes. With this work, we have demonstrated, by in vivo experiments, that the peptide gH625 is able to reduce the side effects of metallic nanoparticle making them more suitable for medical applications.


Asunto(s)
Caenorhabditis elegans/fisiología , Estrés Oxidativo/fisiología , Puntos Cuánticos , Animales , Modelos Biológicos , Péptidos/química , Proteínas del Envoltorio Viral/química
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