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1.
Plant Physiol Biochem ; 208: 108477, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38442626

RESUMO

Tomato fruit consumption is influenced by flavor and nutrient quality. In the present study, we investigate the impact of water saving irrigation (WSI) as a pre-harvest management on flavor and nutrient quality of tomato fruit. Our results demonstrate that WSI-treated tomato fruit exhibited improved sensory scores as assessed by a taste panel, accompanied by elevated levels of SlGLK2 expression, sugars, acids, and carotenoid contents compared to non-treated fruit. Notably, WSI treatment significantly enhanced the development of chloroplast and plastoglobulus in chromoplast, which served as carotenoid storage sites and upregulated the expression of carotenoid biosynthetic genes. Furthermore, integrated transcriptome and metabolome analysis revealed heightened expression of sugar and flavonoid metabolism pathways in WSI-treated tomato fruit. Remarkably, the master regulator SlMYB12 displayed a substantially increased expression due to WSI. These findings suggest that WSI is an effective and sustainable approach to enhance the pigments metabolism and storage capacity as well as the organoleptic characteristics and nutritional value of tomato fruit, offering a win-win solution for both water conservation and quality improvement in agro-food production.


Assuntos
Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Água/metabolismo , Transcriptoma , Carotenoides/metabolismo
2.
Brain Sci ; 14(2)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38391729

RESUMO

Chemical synapses are essential for neuronal information storage and relay. The synaptic signal received or sent from spatially distinct subcellular compartments often generates different outcomes due to the distance or physical property difference. Therefore, the final output of postsynaptic neurons is determined not only by the type and intensity of synaptic inputs but also by the synaptic subcellular location. How synaptic subcellular specificity is determined has long been the focus of study in the neurodevelopment field. Genetic studies from invertebrates such as Caenorhabditis elegans (C. elegans) have uncovered important molecular and cellular mechanisms required for subcellular specificity. Interestingly, similar molecular mechanisms were found in the mammalian cerebellum, hippocampus, and cerebral cortex. This review summarizes the comprehensive advances in the cellular and molecular mechanisms underlying synaptic subcellular specificity, focusing on studies from C. elegans and rodents.

3.
Biomed Opt Express ; 15(1): 77-94, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38223191

RESUMO

Virtual reality (VR) technology has been demonstrated to be effective in rehabilitation training with the assistance of VR games, but its impact on brain functional networks remains unclear. In this study, we used functional near-infrared spectroscopy imaging to examine the brain hemodynamic signals from 18 healthy participants during rest and grasping tasks with and without VR game intervention. We calculated and compared the graph theory-based topological properties of the brain networks using phase locking values (PLV). The results revealed significant differences in the brain network properties when VR games were introduced compared to the resting state. Specifically, for the VR-guided grasping task, the modularity of the brain network was significantly higher than the resting state, and the average clustering coefficient of the motor cortex was significantly lower compared to that of the resting state and the simple grasping task. Correlation analyses showed that a higher clustering coefficient, local efficiency, and modularity were associated with better game performance during VR game participation. This study demonstrates that a VR game task intervention can better modulate the brain functional network compared to simple grasping movements and may be more beneficial for the recovery of grasping abilities in post-stroke patients with hand paralysis.

4.
Vet Sci ; 11(1)2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38250943

RESUMO

Prototheca bovis (P. bovis), an alga that has attracted considerable attention over the years as a causative microorganism of mastitis in dairy cows, exhibits limited susceptibility to specific aminoglycosides and antifungal agents, and no effective clinical treatment is currently available, thereby posing challenges for both prevention and treatment. To investigate the infection of P. bovis mastitis and its impact on raw milk production, a total of 348 raw milk samples were collected from August to December 2022 from a dairy farm in central China. P. bovis and other bacteria were detected, and the average infection rate of P. bovis in raw milk was 60.34% (210/348). The total number of colonies and the somatic cell count (SCC) of P. bovis positive samples were significantly higher than those of P. bovis negative samples (p < 0.01). The daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield of the P. bovis positive samples were significantly lower than those of P. bovis negative samples (p < 0.01). A correlation analysis showed that P. bovis infection was negatively correlated with daily milk yield, 305-day milk yield, peak milk yield, and days to peak milk yield (p < 0.0001), while being positively correlated with the total number of colonies, SCC, milk loss, and protein percentage (p < 0.0001). These findings may help practitioners in comprehending the occurrence of Prototheca mastitis and developing more effective strategies for the prevention of P. bovis infections.

5.
J Cell Biochem ; 124(12): 1919-1930, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37991448

RESUMO

The formation and maintenance of synapses are precisely regulated, and the misregulation often leads to neurodevelopmental or neurodegenerative disorders. Besides intrinsic genetically encoded signaling pathways, synaptic structure and function are also regulated by extrinsic factors, such as nutrients. O-GlcNAc transferase (OGT), a nutrient sensor, is abundant in the nervous system and required for synaptic plasticity, learning, and memory. However, whether OGT is involved in synaptic development and the mechanism underlying the process are largely unknown. In this study, we found that OGT-1, the OGT homolog in C. elegans, regulates the presynaptic assembly in AIY interneurons. The insulin receptor DAF-2 acts upstream of OGT-1 to promote the presynaptic assembly by positively regulating the expression of ogt-1. This insulin-OGT-1 axis functions most likely by regulating neuronal activity. In this study, we elucidated a novel mechanism for synaptic development, and provided a potential link between synaptic development and insulin-related neurological disorders.


Assuntos
Caenorhabditis elegans , Insulina , Animais , Insulina/metabolismo , N-Acetilglucosaminiltransferases/genética , N-Acetilglucosaminiltransferases/metabolismo , Transdução de Sinais
6.
Environ Res ; 231(Pt 1): 116083, 2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37164283

RESUMO

The depth of the substrate of subsurface flow (SSF) constructed wetlands (CWs) is closely related to their cost and operation stability. To explore the physiological regulation mechanism of wetland plants and pollutant removal potential of SSF CWs under "vertical spatial stress of roots" (by greatly reducing the depth of the substrate in SSF CWs to limit the vertical growth space of roots, VSSR), the physiological response and wetland purification effect of a 0.1 m Canna indica L. CW under VSSR were studied compared with conventional SSF CWs (0.6 m, 1.2 m). The results demonstrated that VSSR significantly enhanced the dissolved oxygen (DO) concentration (p < 0.05) within the SSF CWs, with the DO in 0.1 m CW remaining stable at over 3 mg/L. Under the same hydraulic retention time (HRT), VSSR significantly improved the removal effect of pollutants (p < 0.05). The removal rates of COD, NH4+-N, and total phosphorus (TP) remained above 87%, and the mean removal rates of total nitrogen (TN) reached 91.71%. VSSR promoted the morphological adaptation mechanisms of plants, such as significantly increased root-shoot ratio (p < 0.05), changed biomass allocation. Plants could maintain the stability of the photosynthetic mechanism by changing the distribution of light energy. The results of microbial community function prediction demonstrated that aerobic denitrification was the main mechanism of N transformation in the 0.1 m CW under VSSR. VSSR could induce the high root activity of plants, augment the concentration of root exudates, enhance the redox environment of the plant rhizosphere, further foster the enrichment of aerobic denitrifying bacteria, and strengthen the absorption efficiency of wetland plants and substrate, thus achieving an efficient pollutant removal capacity. Studies showed that VSSR was an effective means to enhance the rhizosphere effect of plants and pollutant removal in SSF CWs.


Assuntos
Poluentes Ambientais , Eliminação de Resíduos Líquidos , Eliminação de Resíduos Líquidos/métodos , Áreas Alagadas , Rizosfera , Plantas , Nitrogênio/análise
7.
J Integr Plant Biol ; 65(7): 1794-1813, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37009849

RESUMO

The plant hormone ethylene is essential for climacteric fruit ripening, although it is unclear how other phytohormones and their interactions with ethylene might affect fruit ripening. Here, we explored how brassinosteroids (BRs) regulate fruit ripening in tomato (Solanum lycopersicum) and how they interact with ethylene. Exogenous BR treatment and increased endogenous BR contents in tomato plants overexpressing the BR biosynthetic gene SlCYP90B3 promoted ethylene production and fruit ripening. Genetic analysis indicated that the BR signaling regulators Brassinazole-resistant1 (SlBZR1) and BRI1-EMS-suppressor1 (SlBES1) act redundantly in fruit softening. Knocking out SlBZR1 inhibited ripening through transcriptome reprogramming at the onset of ripening. Combined transcriptome deep sequencing and chromatin immunoprecipitation followed by sequencing identified 73 SlBZR1-repressed targets and 203 SlBZR1-induced targets involving major ripening-related genes, suggesting that SlBZR1 positively regulates tomato fruit ripening. SlBZR1 directly targeted several ethylene and carotenoid biosynthetic genes to contribute to the ethylene burst and carotenoid accumulation to ensure normal ripening and quality formation. Furthermore, knock-out of Brassinosteroid-insensitive2 (SlBIN2), a negative regulator of BR signaling upstream of SlBZR1, promoted fruit ripening and carotenoid accumulation. Taken together, our results highlight the role of SlBZR1 as a master regulator of tomato fruit ripening with potential for tomato quality improvement and carotenoid biofortification.


Assuntos
Brassinosteroides , Solanum lycopersicum , Solanum lycopersicum/genética , Frutas/metabolismo , Etilenos , Reguladores de Crescimento de Plantas , Carotenoides , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas
8.
Anal Chem ; 95(15): 6417-6424, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37031399

RESUMO

Rapid and sensitive detection of foodborne bacteria is of great significance in guaranteeing food safety and preventing foodborne diseases. A bifunctional Au@Pt core-shell nanozyme with excellent catalytic properties and high surface-enhanced Raman scattering (SERS) activity was developed for the highly sensitive detection of Salmonella typhimurium based on a label-free SERS strategy. The ultrathin Pt shell (about 1 nm) can catalyze Raman-inactive molecules into Raman-active reporters, greatly amplifying the amount of signal molecules. Moreover, the Au core serves as an active SERS substrate to enhance the signal of reporter molecules, further significantly improving the detection sensitivity. Benefiting from the excellent properties, such a bifunctional Au@Pt nanozyme was integrated with a magnetic immunoassay to construct a label-free SERS platform for the highly sensitive detection of S. typhi with a low detection limit of 10 CFU mL-1. Also, the Au@Pt-based SERS platform exhibited excellent selectivity and was successfully utilized for the detection of S. typhi in milk samples by a portable Raman spectrometer. Our demonstration of the bifunctional nanozyme-based SERS strategy provides an efficient pathway to improve the sensitivity of label-free SERS detection of pathogens and holds great promise in food safety, environmental analysis, and other biosensing fields.


Assuntos
Técnicas Biossensoriais , Doenças Transmitidas por Alimentos , Nanopartículas Metálicas , Humanos , Animais , Leite , Inocuidade dos Alimentos , Imunoensaio , Análise Espectral Raman , Ouro/química , Nanopartículas Metálicas/química
9.
Neurophotonics ; 10(2): 025001, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37025568

RESUMO

Significance: Motor function evaluation is essential for poststroke dyskinesia rehabilitation. Neuroimaging techniques combined with machine learning help decode a patient's functional status. However, more research is needed to investigate how individual brain function information predicts the dyskinesia degree of stroke patients. Aim: We investigated stroke patients' motor network reorganization and proposed a machine learning-based method to predict the patients' motor dysfunction. Approach: Near-infrared spectroscopy (NIRS) was used to measure hemodynamic signals of the motor cortex in the resting state (RS) from 11 healthy subjects and 31 stroke patients, 15 with mild dyskinesia (Mild), and 16 with moderate-to-severe dyskinesia (MtS). The graph theory was used to analyze the motor network characteristics. Results: The small-world properties of the motor network were significantly different between groups: (1) clustering coefficient, local efficiency, and transitivity: MtS > Mild > Healthy and (2) global efficiency: MtS < Mild < Healthy. These four properties linearly correlated with patients' Fugl-Meyer Assessment scores. Using the small-world properties as features, we constructed support vector machine (SVM) models that classified the three groups of subjects with an accuracy of 85.7%. Conclusions: Our results show that NIRS, RS functional connectivity, and SVM together constitute an effective method for assessing the poststroke dyskinesia degree at the individual level.

10.
Comput Struct Biotechnol J ; 21: 495-505, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36618984

RESUMO

Environmental factors, including temperature, can modulate an animal's lifespan. However, their underlying mechanisms remain largely undefined. We observed a profound effect of temperature on the aging of Caenorhabditis elegans (C. elegans) by performing proteomic analysis at different time points (young adult, middle age, and old age) and temperature conditions (20 °C and 25 °C). Importantly, although at the higher temperature, animals had short life spans, the shift from 20 °C to 25 °C for one day during early adulthood was beneficial for protein homeostasis since; it decreased protein synthesis and increased degradation. Consistent with our findings, animals who lived longer in the 25 °C shift were also more resistant to high temperatures along with oxidative and UV stresses. Furthermore, the lifespan extension by the 25 °C shift was mediated by three important transcription factors, namely FOXO/DAF-16, HSF-1, and HIF-1. We revealed an unexpected and complicated mechanism underlying the effects of temperature on aging, which could potentially aid in developing strategies to treat age-related diseases. Our data are available in ProteomeXchange with the identifier PXD024916.

11.
12.
Front Plant Sci ; 13: 1001756, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36275568

RESUMO

Plastids are a group of diverse organelles with conserved carotenoids synthesizing and sequestering functions in plants. They optimize the carotenoid composition and content in response to developmental transitions and environmental stimuli. In this review, we describe the turbulence and reforming of transcripts, proteins, and metabolic pathways for carotenoid metabolism and storage in various plastid types upon organogenesis and external influences, which have been studied using approaches including genomics, transcriptomics, proteomics, and metabonomics. Meanwhile, the coordination of plastid signaling and carotenoid metabolism including the effects of disturbed carotenoid biosynthesis on plastid morphology and function are also discussed. The "omics" insight extends our understanding of the interaction between plastids and carotenoids and provides significant implications for designing strategies for carotenoid-biofortified crops.

13.
Front Vet Sci ; 9: 846322, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664844

RESUMO

Actinobacillus pleuropneumoniae causes porcine pleuropneumonia. The function of the outer membrane protein W gene (ompW) of A. pleuropneumoniae has not been evaluated. Thus a deletion mutant of ompW, ΔompW, was constructed to explore the effect of ompW gene deletion on bacterial growth, biofilm formation, bacterial morphology, oxidative tolerance, susceptibility to antibiotics, and the expression of ribosome synthesis and ABC transporter related genes. Results showed that the ompW gene deletion did not affect biofilm formation and the growth of A. pleuropneumoniae but did affect bacterial morphology during steady growth, oxidative tolerance, and bacterial susceptibility to polymyxin B, kanamycin, and penicillin. The ompW gene deletion also affected the expression of ribosome synthesis and ABC transporter related genes. These results suggested that ompW may regulate the biological phenotype of A. pleuropneumoniae.

14.
EMBO Rep ; 23(8): e53267, 2022 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-35748387

RESUMO

Synaptic connections are essential to build a functional brain. How synapses are formed during development is a fundamental question in neuroscience. Recent studies provided evidence that the gut plays an important role in neuronal development through processing signals derived from gut microbes or nutrients. Defects in gut-brain communication can lead to various neurological disorders. Although the roles of the gut in communicating signals from its internal environment to the brain are well known, it remains unclear whether the gut plays a genetically encoded role in neuronal development. Using C. elegans as a model, we uncover that a Wnt-endocrine signaling pathway in the gut regulates synaptic development in the brain. A canonical Wnt signaling pathway promotes synapse formation through regulating the expression of the neuropeptides encoding gene nlp-40 in the gut, which functions through the neuronally expressed GPCR/AEX-2 receptor during development. Wnt-NLP-40-AEX-2 signaling likely acts to modulate neuronal activity. Our study reveals a genetic role of the gut in synaptic development and identifies a novel contribution of the gut-brain axis.


Assuntos
Proteínas de Caenorhabditis elegans , Neuropeptídeos , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Neuropeptídeos/genética , Neuropeptídeos/metabolismo , Sinapses/fisiologia , Via de Sinalização Wnt
15.
Antioxidants (Basel) ; 11(1)2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-35052619

RESUMO

Tomato is susceptible to chilling injury during cold storage. In this study, we found that low temperature promoted the expression of brassinosteroid (BR) biosynthetic genes in tomato fruits. The overexpression of SlCYP90B3 (SlCYP90B3-OE), a key BR biosynthetic gene, alleviated the chilling injury with decreased electrical conductivity and malondialdehyde. In SlCYP90B3-OE tomato fruits, the activities of antioxidant enzymes, including ascorbate peroxidase (APX), catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), were markedly increased, while the activity of membranous lipolytic enzymes, lipoxygenase (LOX), and phospholipase D (PLD), were significantly decreased when compared with the wild-type in response to cold storage. Furthermore, the expression level of the cold-response-system component, SlCBF1, was higher in SlCYP90B3-OE fruits than in the wild-type fruits. These results indicated that SlCYP90B3 might be involved in the chilling tolerance of tomato fruits during cold storage, possibly by regulating the antioxidant enzyme system and SlCBF1 expression.

16.
Vet Med Sci ; 8(2): 700-709, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34914190

RESUMO

Arctigenin (ACT) is a novel anti-inflammatory lignan extracted from Arctium lappa L, a herb commonly used in traditional Chinese herbal medicine. In this study, we investigated the molecular mechanism whereby ACT inhibits PCV2 infection-induced proinflammatory cytokine production in vitro and in vivo. We observed that in PCV2 infection+ACT treated PK-15 cells, proinflammatory cytokine production was significantly reduced, compared to the PCV2-infected cells. The transfection and luciferase reporter assay confirmed that ACT suppressed NF-κB signalling pathway activation following PCV2 infection in PK-15 cells. Furthermore, western blotting demonstrated that ACT suppressed the NF-κB signal pathway in PCV2 infection-stimulated PK-15 cells by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation. BALB/c mice were used as a model to evaluate the anti-inflammatory effect of ACT in vivo. We found that the BALB/c mice inoculated with PCV2 infection + ACT treated showed a significant reduction of proinflammatory cytokine production in serum, lung and spleen tissue, compared to the PCV2-infected mice. Western blotting confirmed that ACT suppressed the NF-κB signal pathway in PCV2-infected mice by inhibiting the translocation of p65 from the cytoplasm to the nucleus and IκBα phosphorylation in lung tissue. Our studies first demonstrate that ACT inhibits PCV2 infection-induced proinflammatory cytokine production by suppressing the phosphorylation and nuclear translocation of NF-κB in vitro and in vivo. These results will help further develop ACT as a Traditional Chinese herbal medicine remedy in the treatment of porcine circovirus-associated diseases.


Assuntos
Infecções por Circoviridae , Medicamentos de Ervas Chinesas , Furanos , Lignanas , NF-kappa B , Animais , Anti-Inflamatórios/farmacologia , Infecções por Circoviridae/tratamento farmacológico , Citocinas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Furanos/farmacologia , Lignanas/farmacologia , Camundongos , Camundongos Endogâmicos BALB C , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/metabolismo , Suínos
17.
Hum Mol Genet ; 31(1): 57-68, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34346496

RESUMO

Ogt-mediated O-GlcNAcylation is enriched in the nervous system and involves in neuronal development, brain function and neurological diseases. However, the roles of Ogt and O-GlcNAcylation in embryonic neurogenesis have remained largely unknown. Here, we show that Ogt is highly expressed in embryonic brain, and Ogt depletion reduces the proliferation of embryonic neural stem cells and migration of new born neurons. Ogt depletion in cultured hippocampal neurons impairs neuronal maturation, including reduced dendritic numbers and length, and immature development of spines. Mechanistically, Ogt depletion decreases the activity of Wnt/ß-catenin signaling. Ectopic ß-catenin rescues neuronal developmental deficits caused by Ogt depletion. Ogt also regulates human cortical neurogenesis in forebrain organoids derived from induced pluripotent stem cells. Our findings reveal the essential roles and mechanisms of Ogt-mediated O-GlcNAc modification in regulating mammalian neuronal development.


Assuntos
N-Acetilglucosaminiltransferases , beta Catenina , Animais , Humanos , Mamíferos , N-Acetilglucosaminiltransferases/genética , Neurogênese/genética , Neurônios , beta Catenina/genética
18.
iScience ; 24(8): 102926, 2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34430815

RESUMO

Fruit softening indicated by firmness determines the texture, transportability, and shelf life of tomato products. However, the regulatory mechanism underlying firmness formation in tomato fruit is poorly understood. Here, we report the regulatory role of SlBES1, an essential component of brassinosteroid hormone signaling, in tomato fruit softening. We found that SlBES1 promotes fruit softening during tomato fruit ripening and postharvest storage. RNA-seq analysis suggested that PMEU1, which encodes a pectin methylesterase, might participate in SlBES1-mediated softening. Biochemical and immunofluorescence assays indicated that SlBES1 inhibited PMEU1-related pectin de-methylesterification. Further molecular and genetic evidence verified that SlBES1 directly binds to the E-box of PMEU1 to repress its expression, leading to fruits softening. Loss-of-function SlBES1 mutant generated by CRISPR-Cas9 showed firmer fruits and longer shelf life during postharvest storage without other quality alteration. Collectively, our results indicated the potential of manipulating SlBES1 to regulate firmness without negative consequence on visual and nutrition quality.

19.
J Vet Med Sci ; 83(8): 1248-1255, 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34193721

RESUMO

Bovine mastitis, caused by Prototheca bovis, has received much attention worldwide. To investigate the status of P. bovis infection in dairy farms of Hubei, we collected 1,158 milk samples and 90 environmental samples from 14 dairy farms of Hubei, China. The isolates were identified with traditional biological methods and molecular biological techniques, and their pathogenicity was tested through mice infection experiments. Isolates from 57 milk and 20 environmental samples were identified as P. bovis. The mice infection tests proved that the isolated P. bovis could cause mastitis in mice, manifesting as severe red swelling of the mammary glands. Histopathological analysis of tissue sections showed necrosis and nodules lesions formed in the infected mice mammary tissue, accompanied by macrophage and neutrophil infiltration. These results suggested the existence of pathogenic P. bovis in dairy farms of the Hubei province, China, with brewer's grains and fresh feces possibly playing important roles in the spread of this disease.


Assuntos
Doenças dos Bovinos , Mastite Bovina , Mastite , Prototheca , Doenças dos Roedores , Animais , Bovinos , Doenças dos Bovinos/epidemiologia , Fazendas , Feminino , Mastite/veterinária , Mastite Bovina/epidemiologia , Camundongos , Leite
20.
PLoS One ; 16(7): e0249103, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34242227

RESUMO

During development, homeostasis, and disease, organisms must balance responses that allow adaptation to low oxygen (hypoxia) with those that protect cells from oxidative stress. The evolutionarily conserved hypoxia-inducible factors are central to these processes, as they orchestrate transcriptional responses to oxygen deprivation. Here, we employ genetic strategies in C. elegans to identify stress-responsive genes and pathways that modulate the HIF-1 hypoxia-inducible factor and facilitate oxygen homeostasis. Through a genome-wide RNAi screen, we show that RNAi-mediated mitochondrial or proteasomal dysfunction increases the expression of hypoxia-responsive reporter Pnhr-57::GFP in C. elegans. Interestingly, only a subset of these effects requires hif-1. Of particular importance, we found that skn-1 RNAi increases the expression of hypoxia-responsive reporter Pnhr-57::GFP and elevates HIF-1 protein levels. The SKN-1/NRF transcription factor has been shown to promote oxidative stress resistance. We present evidence that the crosstalk between HIF-1 and SKN-1 is mediated by EGL-9, the prolyl hydroxylase that targets HIF-1 for oxygen-dependent degradation. Treatment that induces SKN-1, such as heat or gsk-3 RNAi, increases expression of a Pegl-9::GFP reporter, and this effect requires skn-1 function and a putative SKN-1 binding site in egl-9 regulatory sequences. Collectively, these data support a model in which SKN-1 promotes egl-9 transcription, thereby inhibiting HIF-1. We propose that this interaction enables animals to adapt quickly to changes in cellular oxygenation and to better survive accompanying oxidative stress.


Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Fator 1 Induzível por Hipóxia/metabolismo , Animais , Caenorhabditis elegans/genética , Estresse Oxidativo , Transcrição Gênica
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