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The heterogeneous nuclear ribonucleoprotein hnRNP A1 is a nucleocytoplasmic-shuttling RNA-binding protein that plays an important role in nucleic acid metabolism and gene expression regulation. The function of hnRNP A1 is determined in part by its specific location within the cell. Although some work has been done to elucidate the signaling pathways that regulate the cellular localization of hnRNP A1, the precise mechanism(s), including physiological and pathophysiological conditions that alter hnRNP A1 localization, are not known. We previously conducted an unbiased RNAi-based kinome-wide screen to identify kinases that regulate hnRNP A1 localization during hypertonic stress. One of the hits from this screen is AMPK-related protein kinase 5 (ARK5). Here, we validate ARK5 as the kinase responsible for controlling hnRNP A1 subcellular localization in response to hypertonic stress. We find using immunoprecipitation and in vitro kinase assay methods that ARK5 directly interacts with and phosphorylates hnRNP A1 on serine residues within the F-peptide region. We further show that the M9 motif of hnRNP A1 is essential for the ARK5-hnRNP A1 interaction and subsequent phosphorylation. In addition, the silencing of ARK5 increases the expression of antiapoptotic protein Bcl-xL and consequently delays caspase activation during hypertonic stress. Our results indicate that ARK5 phosphorylates hnRNP A1 and regulates its subcellular localization during hypertonic stress.
Assuntos
Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B , Ácidos Nucleicos , Proteínas Quinases Ativadas por AMP/metabolismo , Caspases/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/genética , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas , Pressão Osmótica , SerinaRESUMO
Hypoxia-inducible factor-1α (HIF-1α) is an important regulator of glucose metabolism and inflammatory cytokine production in innate immune responses. Viruses modulate HIF-1α to support viral replication and the survival of infected cells, but it is unclear if this transcription factor also plays an important role in regulating antiviral immune responses. In this study, we found that short and long dsRNA differentially engage TLR3, inducing distinct levels of proinflammatory cytokine production (TNF-α and IL-6) in bone marrow-derived macrophages from C57BL/6 mice. These responses are associated with differential accumulation of HIF-1α, which augments NF-κB activation. Unlike TLR4 responses, increased HIF-1α following TLR3 engagement is not associated with significant alterations in glycolytic activity and was more pronounced in low glucose conditions. We also show that the mechanisms supporting HIF-1α stabilization may differ following stimulation with short versus long dsRNA and that pyruvate kinase M2 and mitochondrial reactive oxygen species play a central role in these processes. Collectively, this work suggests that HIF-1α may fine-tune proinflammatory cytokine production during early antiviral immune responses, particularly when there is limited glucose availability or under other conditions of stress. Our findings also suggest we may be able to regulate the magnitude of proinflammatory cytokine production during antiviral responses by targeting proteins or molecules that contribute to HIF-1α stabilization.
Assuntos
Citocinas/biossíntese , Glucose/imunologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/imunologia , Macrófagos/imunologia , Ácidos Nucleicos/imunologia , Receptor 3 Toll-Like/imunologia , Animais , Células Cultivadas , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/imunologiaRESUMO
Nanoparticles (NPs) are increasingly used in a wide variety of applications and products; however, NPs may affect stress response pathways and interact with proteins in biological systems. This review article will provide an overview of the beneficial and detrimental effects of NPs on stress response pathways with a focus on NP-protein interactions. Depending upon the particular NP, experimental model system, and dose and exposure conditions, the introduction of NPs may have either positive or negative effects. Cellular processes such as the development of oxidative stress, the initiation of the inflammatory response, mitochondrial function, detoxification, and alterations to signaling pathways are all affected by the introduction of NPs. In terms of tissue-specific effects, the local microenvironment can have a profound effect on whether an NP is beneficial or harmful to cells. Interactions of NPs with metal-binding proteins (zinc, copper, iron and calcium) affect both their structure and function. This review will provide insights into the current knowledge of protein-based nanotoxicology and closely examines the targets of specific NPs.
Assuntos
Nanopartículas Metálicas , Nanopartículas , Nanopartículas Metálicas/química , Nanopartículas/química , Estresse Oxidativo , Transdução de SinaisRESUMO
Temperature is critical in regulating virtually all biological functions in fish. Low temperature stress (cold shock/stress) is an often-overlooked challenge that many fish face as a result of both natural events and anthropogenic activities. In this study, we present an updated review of the cold shock literature based on a comprehensive literature search, following an initial review on the subject by M.R. Donaldson and colleagues, published in a 2008 volume of this journal. We focus on how knowledge on cold shock and fish has evolved over the past decade, describing advances in the understanding of the generalized stress response in fish under cold stress, what metrics may be used to quantify cold stress and what knowledge gaps remain to be addressed in future research. We also describe the relevance of cold shock as it pertains to environmental managers, policymakers and industry professionals, including practical applications of cold shock. Although substantial progress has been made in addressing some of the knowledge gaps identified a decade ago, other topics (e.g., population-level effects and interactions between primary, secondary and tertiary stress responses) have received little or no attention despite their significance to fish biology and thermal stress. Approaches using combinations of primary, secondary and tertiary stress responses are crucial as a research priority to better understand the mechanisms underlying cold shock responses, from short-term physiological changes to individual- and population-level effects, thereby providing researchers with better means of quantifying cold shock in laboratory and field settings.
Assuntos
Resposta ao Choque Frio , Peixes , Animais , Temperatura Baixa , TemperaturaRESUMO
Localized hyperthermia therapy involves heating a small volume of tissue in order to kill cancerous cells selectively and with limited damage to healthy cells and surrounding tissue. However, these features are only achievable through real-time control of the tissue temperature and heated volume, both of which are difficult to obtain with current heating systems and techniques. This work introduces an optical fiber-based active heater that acts both as a miniature heat source and as a thermometer. The heat-induced damage in the tissue is caused by the conductive heat transfer from the surface of the device, while the heat is generated in an absorptive coating on the fiber by near-infrared light redirected from the fiber core to the surface by a tilted fiber Bragg grating inscribed in the fiber core. Simultaneous monitoring of the reflection spectrum of the grating provides a measure of the local temperature. Localized temperature increases between 0°C and 100°C in 10 mm-long/5 mm-diameter cylindrical volumes are obtained with continuous-wave pump power levels up to 1.8 W. Computational and experimental results further indicate that the temperature rise and dimensions of the heated volume can be maintained at a nearly stable level determined by the input optical power.
Assuntos
Tecnologia de Fibra Óptica/instrumentação , Hipertermia/diagnóstico , Animais , Morte Celular , Linhagem Celular , Simulação por Computador , Clara de Ovo/análise , Tecnologia de Fibra Óptica/métodos , Temperatura Alta , Humanos , Técnicas In Vitro , Raios Infravermelhos , Fígado/metabolismo , Modelos Químicos , Fibras Ópticas , Suínos , TemperaturaRESUMO
The Publisher regrets that this article is an accidental duplication of an article that has already been published in Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology, Volume 255, 2021, 110593, https://doi.org/10.1016/j.cbpb.2021.110593. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.
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The aim of this study was to investigate the detailed mechanisms of hepatotoxicity induced by cadmium telluride quantum dots (CdTe-QDs) in BALB/c mice after intravenous injection. The study investigated oxidative stress, apoptosis, and effects on mitochondria as potential mechanistic events to elucidate the observed hepatotoxicity. Oxidative stress in the liver, induced by CdTe-QD exposure, was demonstrated by depletion of total glutathione, an increase in superoxide dismutase activity, and changes in the gene expression of several oxidative stress-related biomarkers. Furthermore, CdTe-QD treatment led to apoptosis in the liver via both intrinsic and extrinsic apoptotic pathways. Effects on mitochondria were evidenced by the enlargement and increase in the number of mitochondria in hepatocytes of treated mice. CdTe-QDs also caused changes in the levels and gene expression of electron transport chain enzymes, depletion of ATP, and an increase in the level of the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), a regulator of mitochondrial biogenesis. The findings from this study suggest that CdTe-QDs-induced hepatotoxicity might have originated from mitochondrial effects which resulted in oxidative stress and apoptosis in the liver cells. This study provides insight into the biological effects of CdT-QDs at the tissue level and the detailed mechanisms of their toxicity in animals. The study also provides important data for bridging the gap between in vitro and in vivo testing and risk assessment of these NPs.
Assuntos
Compostos de Cádmio/toxicidade , Hepatócitos/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Pontos Quânticos/toxicidade , Telúrio/toxicidade , Animais , Relação Dose-Resposta a Droga , Hepatócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mitocôndrias/metabolismoRESUMO
Quantum dots (QDs) are engineered nanoparticles (NPs) of semiconductor structure that possess unique optical and electronic properties and are widely used in biomedical applications; however, their risks are not entirely understood. This study investigated the tissue distribution and toxic effects of cadmium telluride quantum dots (CdTe-QDs) in male BALB/c mice for up to 1 week after single-dose intravenous injections. CdTe-QDs were detected in the blood, lung, heart, liver, spleen, kidney, testis and brain. Most CdTe-QDs accumulated in the liver, followed by the spleen and kidney. At high doses, exposure to CdTe-QDs resulted in mild dehydration, lethargy, ruffled fur, hunched posture, and body weight loss. Histological analysis of the tissues, upon highest dose exposures, revealed hepatic hemorrhage and necrotic areas in the spleen. The sera of mice treated with high doses of CdTe-QDs showed significant increases in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin levels, as well as a reduction in albumin. CdTe-QD exposure also led to a reduced number of platelets and elevated total white blood cell counts, including monocytes and neutrophils, serum amyloid A, and several pro-inflammatory cytokines. These results demonstrated that the liver is the main target of CdTe-QDs and that exposure to CdTe-QDs leads to hepatic and splenic injury, as well as systemic effects, in mice. By contrast, cadmium chloride (CdCl2), at an equivalent concentration of cadmium, appeared to have a different pharmacokinetic pattern from that of CdTe-QDs, having minimal effects on the aforementioned parameters, suggesting that cadmium alone cannot fully explain the toxicity of CdTe-QDs.
Assuntos
Compostos de Cádmio/farmacocinética , Nanopartículas/química , Pontos Quânticos/química , Telúrio/farmacocinética , Alanina Transaminase/química , Alanina Transaminase/metabolismo , Albuminas/química , Albuminas/metabolismo , Animais , Aspartato Aminotransferases/química , Aspartato Aminotransferases/metabolismo , Bilirrubina/sangue , Cloreto de Cádmio/administração & dosagem , Cloreto de Cádmio/metabolismo , Cloreto de Cádmio/farmacocinética , Compostos de Cádmio/administração & dosagem , Compostos de Cádmio/metabolismo , Injeções Intravenosas , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Nanopartículas/metabolismo , Pontos Quânticos/metabolismo , Telúrio/administração & dosagem , Telúrio/metabolismo , Distribuição TecidualRESUMO
We demonstrate a DNA-based optical fiber device that uses an in-fiber grating, a light absorbing coating with surface anchored DNA, and a built-in optical thermometer. This device is used for precisely thermal cycling surface DNA spots bound by a simple UV cross-linking technique. Near-infrared light of wavelengths near 1550 nm and guided power near 300 mW is coupled out of the fiber core by a tilted fiber Bragg grating inscribed in the fiber and absorbed by the coating to increase its temperature to more than 95 °C. A co-propagating broadband light signal (also in the near-infrared region) is used to measure the reflection spectrum of the grating and thus the temperature from the wavelength shifts of the reflection peaks. The device is capable of sensitive DNA melt analysis and can be used for DNA amplification. Graphical abstract.
Assuntos
Técnicas Biossensoriais/instrumentação , DNA/química , Tecnologia de Fibra Óptica/instrumentação , Hibridização de Ácido Nucleico , DNA/genética , Desenho de Equipamento , Calefação , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/genética , Desnaturação de Ácido Nucleico , Fibras ÓpticasRESUMO
Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is a highly brominated additive flame retardant (FR). Debrominated photodegradates of TeDB-DiPhOBz are hydroxylated in vitro in liver microsomal assays based on herring gulls (Larus argentatus), including one metabolite identified as 4â³-OH-2,2',2â³,4-tetrabromo-DiPhOBz. Chemically related methoxylated tetra- to hexabromo-DiPhOBzs are known contaminants in herring gulls. Collectively, nothing is currently known about biological effects of these polybrominated (PB) DiPhOBz-based compounds. The present study investigated the potential thyroidogenicity of 2,2',2â³,4-tetrabromo-(TB)-DiPhOBz along with its para-methoxy (MeO)- and hydroxy-(OH)-analogues, using an in vitro competitive protein binding assay with the human thyroid hormone (TH) transport proteins transthyretin (hTTR) and albumin (hALB). This model para-OH-TB-DiPhOBz was found to be capable of competing with thyroxine (T4) for the binding site on hTTR and hALB. In silico analyses were also conducted using a 3D homology model for gull TTR, to predict whether these TB-DiPhOBz-based compounds may also act as ligands for an avian TH transport protein despite evolutionary differences with hTTR. This analysis found all three TB-DiPhOBz analogues to be potential ligands for gull TTR and have similar binding efficacies to THs. Results indicate structure-related differences in binding affinities of these ligands and suggest there is potential for these contaminants to interact with both mammalian and avian thyroid function.
Assuntos
Charadriiformes , Retardadores de Chama , Animais , Ligação Competitiva , Éter , Éteres , HumanosRESUMO
Experimental and/or epidemiological studies suggest that prenatal exposure to bisphenol A (BPA) may delay fetal lung development and maturation and increase the susceptibility to childhood respiratory disease. However, the underlying mechanisms remain to be elucidated. In our previous study with cultured human fetal lung fibroblasts (HFLF), we demonstrated that 24-h exposure to 1 and 100 µM BPA increased GPR30 protein in the nuclear fraction. Exposure to 100 µM BPA had no effects on cell viability, but increased cytoplasmic expression of ERß and release of GDF-15, as well as decreased release of IL-6, ET-1, and IP-10 through suppression of NFκB phosphorylation. By performing global gene expression and pathway analysis in this study, we identified molecular pathways, gene networks, and key molecules that were affected by 100, but not 0.01 and 1 µM BPA in HFLF. Using multiple genomic and proteomic tools, we confirmed these changes at both gene and protein levels. Our data suggest that 100 µM BPA increased CYP1B1 and HSD17B14 gene and protein expression and release of endogenous estradiol, which was associated with increased ROS production and DNA double-strand breaks, upregulation of genes and/or proteins in steroid synthesis and metabolism, and activation of Nrf2-regulated stress response pathways. In addition, BPA activated ATM-p53 signaling pathway, resulting in increased cell cycle arrest at G1 phase, senescence and autophagy, and decreased cell proliferation in HFLF. The results suggest that prenatal exposure to BPA at certain concentrations may affect fetal lung development and maturation, and thereby affecting susceptibility to childhood respiratory diseases.
Assuntos
17-Hidroxiesteroide Desidrogenases/genética , Poluentes Ocupacionais do Ar/toxicidade , Compostos Benzidrílicos/toxicidade , Citocromo P-450 CYP1B1/genética , Estradiol/metabolismo , Pulmão/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Fenóis/toxicidade , Proteína Supressora de Tumor p53/metabolismo , 17-Hidroxiesteroide Desidrogenases/metabolismo , Autofagia , Pontos de Checagem do Ciclo Celular , Senescência Celular/efeitos dos fármacos , Citocromo P-450 CYP1B1/metabolismo , Fibroblastos/efeitos dos fármacos , Humanos , Espécies Reativas de Oxigênio/metabolismo , Regulação para CimaRESUMO
Emerging evidence suggests that cellular metabolism plays a critical role in regulating immune activation. Alterations in energy and lipid and amino acid metabolism have been shown to contribute to type I interferon (IFN) responses in macrophages, but the relationship between metabolic reprogramming and the establishment of early antiviral function remains poorly defined. Here, we used transcriptional profiling datasets to develop global metabolic signatures associated with early IFN-α responses in two primary macrophage model systems: mouse bone marrow-derived macrophages (BMM) and human monocyte-derived macrophages (MDM). Short-term stimulation with IFN-α (<4 hours) was associated with significant metabolic rewiring, with >500 metabolic genes altered in mouse and human macrophage models. Pathway and network analysis identified alterations in genes associated with cellular bioenergetics, cellular oxidant status, cAMP/AMP and cGMP/GMP ratios, branched chain amino acid catabolism, cell membrane composition, fatty acid synthesis, and ß-oxidation as key features of early IFN-α responses. These changes may have important implications for initial establishment of antiviral function in these cells.
Assuntos
Interferon-alfa/farmacologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Animais , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Humanos , Interferon Tipo I/farmacologia , Camundongos , Transdução de Sinais/efeitos dos fármacosRESUMO
Nanosilver plays an important role in nanoscience and nanotechnology, and is becoming increasingly used for applications in nanomedicine. Nanosilver ranges from 1 to 100 nanometers in diameter. Smaller particles more readily enter cells and interact with the cellular components. The exposure dose, particle size, coating, and aggregation state of the nanosilver, as well as the cell type or organism on which it is tested, are all large determining factors on the effect and potential toxicity of nanosilver. A high exposure dose to nanosilver alters the cellular stress responses and initiates cascades of signalling that can eventually trigger organelle autophagy and apoptosis. This review summarizes the current knowledge of the effects of nanosilver on cellular metabolic function and response to stress. Both the causative effects of nanosilver on oxidative stress, endoplasmic reticulum stress, and hypoxic stress-as well as the effects of nanosilver on the responses to such stresses-are outlined. The interactions and effects of nanosilver on cellular uptake, oxidative stress (reactive oxygen species), inflammation, hypoxic response, mitochondrial function, endoplasmic reticulum (ER) function and the unfolded protein response, autophagy and apoptosis, angiogenesis, epigenetics, genotoxicity, and cancer development and tumorigenesis-as well as other pathway alterations-are examined in this review.
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Nanopartículas Metálicas/uso terapêutico , Neoplasias/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Prata/uso terapêutico , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Dano ao DNA , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Humanos , Nanopartículas Metálicas/química , Neoplasias/metabolismo , Neoplasias/patologia , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Estresse Oxidativo/efeitos dos fármacos , Prata/químicaRESUMO
Levels of oxidative stress can be affected by a range of compounds including toxins and pharmaceuticals. Antioxidants are important protective compounds which counteract the damaging effects of oxidative stress. Glutathione (GSH) is one of the main antioxidants for many organisms and can be synthesized from administered N-acetylcysteine (NAC). NAC has therefore often been used in a wide range of taxa to manipulate levels of GSH. Our objective was to validate this approach in a wild temperate teleost fish model, the brown trout (Salmo trutta). We used intracoelomic injections of NAC in saline and vegetable shortening, at two different concentrations (100 and 400 mg/kg), with the appropriate controls and shams, under controlled laboratory settings. We found that NAC failed to elicit an increase in GSH over three time periods and concluded that NAC is not an effective method to enhance GSH levels in teleost fish using the concentrations and vehicles tested here. We emphasize the importance of validation studies across all new species/taxa when possible and suggest that more investigation is required with regard to NAC manipulation in fish if this approach is to be used.
Assuntos
Acetilcisteína/farmacologia , Glutationa/metabolismo , Truta/metabolismo , Acetilcisteína/administração & dosagem , Animais , Relação Dose-Resposta a Droga , Estresse Oxidativo/efeitos dos fármacosRESUMO
Folates are B-vitamins that play an important role in brain function. Dietary and genetic deficiencies in folate metabolism result in elevated levels of homocysteine which have been linked to increased risk of developing a stroke. Reducing levels of homocysteine before or after a stroke through B-vitamin supplementation has been a focus of many clinical studies, however, the results remain inconsistent. Animal model systems provide a powerful mechanism to study and understand functional impact and mechanisms through which supplementation affects stroke recovery. The aim of this study was to understand the role of B-vitamins in stroke pathology using in vivo and in vitro mouse models. The first objective assessed the impact of folate deficiency prior to ischemic damage followed by B-vitamins and choline supplementation. Ischemic damage targeted the sensorimotor cortex. C57Bl/6 wild-type mice were maintained on a folic acid deficient diet for 4weeks prior to ischemic damage to increased levels of plasma homocysteine, a risk factor for stroke. Post-operatively mice were placed on a B-vitamin and choline supplemented diet for a period of four weeks, after which motor function was assessed in mice using the rotarod, ladder beam and forepaw asymmetry tasks. The second objective was to determine how a genetic deficiency in methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in folate metabolism, increases vulnerability to stroke. Primary cortical neurons were isolated from Mthfr+/+, Mthfr+/- and Mthfr-/- embryos and were exposed to in vitro models of stroke which include hypoxia or oxygen glucose deprivation. Cell viability was measured 24-h after exposure stroke like conditions in vitro. In supplemented diet mice, we report improved motor function after ischemic damage compared to mice fed a control diet after ischemic damage. Within the perilesional cortex, we show enhanced proliferation, neuroplasticity and anti-oxidant activity in mice fed the supplemented diet. A genetic MTHFR deficiency resulted in neurodegeneration after exposure to in vitro models of stroke, by activating apoptosis promoting p53-dependent mechanisms. These results suggest that one-carbon metabolism plays a significant role in recovery after stroke and MTHFR deficiency contributes to poor recovery from stroke.
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Colina/administração & dosagem , Suplementos Nutricionais , Plasticidade Neuronal/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/dietoterapia , Complexo Vitamínico B/administração & dosagem , Animais , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Camundongos , Camundongos Endogâmicos C57BL , Plasticidade Neuronal/fisiologia , Distribuição Aleatória , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/metabolismo , Acidente Vascular Cerebral/patologiaRESUMO
In the wild, animals are exposed to a growing number of stressors with increasing frequency and intensity, as a result of human activities and human-induced environmental change. To fully understand how wild organisms are affected by stressors, it is crucial to understand the physiology that underlies an organism's response to a stressor. Prolonged levels of elevated glucocorticoids are associated with a state of chronic stress and decreased fitness. Exogenous glucocorticoid manipulation reduces an individual's ability to forage, avoid predators and grow, thereby limiting the resources available for physiological functions like defence against oxidative stress. Using brown trout (Salmo trutta), we evaluated the short-term (2â weeks) and long-term (4â months over winter) effects of exogenous cortisol manipulations (versus relevant shams and controls) on the oxidative status of wild juveniles. Cortisol caused an increase in glutathione over a 2 week period and appeared to reduce glutathione over winter. Cortisol treatment did not affect oxidative stress levels or low molecular weight antioxidants. Cortisol caused a significant decrease in growth rates but did not affect predation risk. Over-winter survival in the stream was associated with low levels of oxidative stress and glutathione. Thus, oxidative stress may be a mechanism by which elevated cortisol causes negative physiological effects.
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Hidrocortisona/farmacologia , Estresse Oxidativo , Truta/metabolismo , Animais , Antioxidantes/metabolismo , Dinamarca , Glutationa/metabolismo , Estações do Ano , Truta/crescimento & desenvolvimentoRESUMO
Physiologically, oxidative stress is considered a homeostatic imbalance between reactive oxygen species production and absorption. From an ecological perspective, oxidative stress may serve as an important constraint to life-history traits, such as lifespan, reproduction and the immune system, and is gaining interest as a potential mechanism underlying life-history trade-offs. Of late, there has been much interest in understanding the role of oxidative stress in the ecology of wild animals, particularly during challenging periods such as reproduction. Here, we used a long-term study population of a fish with sole-male parental care, the smallmouth bass, Micropterus dolomieu, to examine the associations among oxidative stress indicators and life-history variables in nest-guarding males. In addition, we investigated the potential role of oxidative stress as a physiological mediator of the life-history trade-off decision of paternal smallmouth bass to stay with or abandon their brood. We found that oxidative stress was significantly related to the life history of paternal smallmouth bass, such that older, larger fish with greater reproductive experience and larger broods nesting in cooler water temperatures had lower levels of oxidative stress. However, we found no significant correlation between oxidative stress and nesting success, suggesting that oxidative stress may not be involved in the decision of male smallmouth bass to abandon their brood. Wild fish have been relatively understudied in the emerging field of oxidative ecology, and this study makes noteworthy contributions by revealing interesting connections between the life histories of paternal smallmouth bass and their oxidative status.
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Bass/fisiologia , Comportamento de Nidação/fisiologia , Estresse Oxidativo/fisiologia , Comportamento Paterno/fisiologia , Fatores Etários , Animais , Dano ao DNA , Ecossistema , Estágios do Ciclo de Vida , Masculino , Ontário , TemperaturaRESUMO
The "cap'n'collar" bZIP transcription factor Nrf1 heterodimerizes with small Maf proteins to bind to the Antioxidant Response Element/Electrophile Response Element to transactivate antioxidant enzyme, phase 2 detoxification enzyme and proteasome subunit gene expression. Nrf1 specifically regulates pathways in lipid metabolism, amino acid metabolism, proteasomal degradation, the citric acid cycle, and the mitochondrial respiratory chain. Nrf1 is maintained in the endoplasmic reticulum (ER) in an inactive glycosylated state. Activation involves retrotranslocation from the ER lumen to the cytoplasm, deglycosylation and partial proteolytic processing to generate the active forms of Nrf1. Recent evidence has revealed how this factor is regulated and its involvement in various metabolic diseases. This review outlines Nrf1 structure, function, regulation and its links to insulin resistance, diabetes and inflammation. The glycosylation/deglycosylation of Nrf1 is controlled by glucose levels. Nrf1 glycosylation affects its control of glucose transport, glycolysis, gluconeogenesis and lipid metabolism.
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Diabetes Mellitus/genética , Glucose/metabolismo , Inflamação/genética , Fator 1 Nuclear Respiratório/genética , Aminoácidos/genética , Aminoácidos/metabolismo , Ciclo do Ácido Cítrico/genética , Diabetes Mellitus/metabolismo , Glicosilação , Humanos , Inflamação/metabolismo , Resistência à Insulina/genética , Metabolismo dos Lipídeos/genética , Fator 1 Nuclear Respiratório/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Complexo de Endopeptidases do Proteassoma/metabolismo , ProteóliseRESUMO
Significant sensitivity enhancements in the tandem mass spectrometry-based analysis of complex mixtures of several phospholipid classes has been achieved via (13)C-TrEnDi. (13)C-TrEnDi-modified phosphatidylethanolamine (PE), phosphatidylserine (PS), and phosphatidylcholine (PC) lipids extracted from HeLa cells demonstrated greater sensitivity via precursor ion scans (PISs) than their unmodified counterparts. Sphingomyelin (SM) species exhibited neither an increased nor decreased sensitivity following modification. The use of isotopically labeled diazomethane enabled the distinction of modified PE and modified PC species that would yield isobaric species with unlabeled diazomethane. (13)C-TrEnDi created a PE-exclusive PIS of m/z 202.1, two PS-exclusive PISs of m/z 148.1 and m/z 261.1, and a PIS of m/z 199.1 for PC species (observed at odd m/z values) and SM species (observed at even m/z values). The standardized average area increase after TrEnDi modification was 10.72-fold for PE species, 2.36-fold for PC, and 1.05-fold for SM species. The sensitivity increase of PS species was not quantifiable, as there were no unmodified PS species identified prior to derivatization. (13)C-TrEnDi allowed for the identification of 4 PE and 7 PS species as well as the identification and quantitation of an additional 4 PE and 4 PS species that were below the limit of detection (LoD) prior to modification. (13)C-TrEnDi also pushed 24 PE and 6 PC lipids over the limit of quantitation (LoQ) that prior to modification were above the LoD only.
Assuntos
Diazometano/química , Fosfatidilcolinas/análise , Fosfatidiletanolaminas/análise , Fosfatidilserinas/análise , Isótopos de Carbono , Células HeLa , Humanos , Limite de Detecção , Metilação , Fosfatidilcolinas/química , Fosfatidilcolinas/classificação , Fosfatidiletanolaminas/química , Fosfatidiletanolaminas/classificação , Fosfatidilserinas/química , Fosfatidilserinas/classificação , Sensibilidade e Especificidade , Espectrometria de Massas por Ionização por Electrospray/métodosRESUMO
Maternally-derived hormones in oocytes, such as glucocorticoids (GCs), play a crucial role in embryo development in oviparous taxa. In fishes, maternal stressor exposure increases circulating and egg cortisol levels, the primary GC in fishes, as well as induces oxidative stress. Elevated egg cortisol levels modify offspring traits but whether maternal oxidative stress correlates with circulating and egg cortisol levels, and whether maternal/egg cortisol levels correlate with offspring oxidative stress have yet to be determined. The objective of this study was to examine the relationships among maternal and egg cortisol, and maternal and offspring oxidative stress to provide insight into the potential intergenerational effects of stressor exposure in sockeye salmon (Oncorhynchus nerka). Antioxidant concentration and oxidative stress were measured in maternal tissues (plasma, brain, heart and liver) as well as offspring developmental stages (pre-fertilization, 24h post-fertilization, eyed, and hatch), and were compared to both naturally-occurring and experimentally-elevated (via cortisol egg bath) levels of cortisol in eggs. Oxygen radical absorptive capacity of tissues from maternal sockeye salmon was measured spectrophotometrically and was not correlated with maternal or egg cortisol concentrations. Also, naturally-occurring and experimentally-elevated cortisol levels in eggs (to mimic maternal stress) did not affect oxidative stress or antioxidant capacity of the offspring. We conclude that the metrics of maternal stress examined in sockeye salmon (i.e., maternal/egg cortisol, maternal oxidative stress) are independent of each other, and that egg cortisol content does not influence offspring oxidative stress.