RESUMO
OBJECTIVE: To determine whether a single low dose of esketamine administered after childbirth reduces postpartum depression in mothers with prenatal depression. DESIGN: Randomised, double blind, placebo controlled trial with two parallel arms. SETTING: Five tertiary care hospitals in China, 19 June 2020 to 3 August 2022. PARTICIPANTS: 364 mothers aged ≥18 years who had at least mild prenatal depression as indicated by Edinburgh postnatal depression scale scores of ≥10 (range 0-30, with higher scores indicating worse depression) and who were admitted to hospital for delivery. INTERVENTIONS: Participants were randomly assigned 1:1 to receive either 0.2 mg/kg esketamine or placebo infused intravenously over 40 minutes after childbirth once the umbilical cord had been clamped. MAIN OUTCOME MEASURES: The primary outcome was prevalence of a major depressive episode at 42 days post partum, diagnosed using the mini-international neuropsychiatric interview. Secondary outcomes included the Edinburgh postnatal depression scale score at seven and 42 days post partum and the 17 item Hamilton depression rating scale score at 42 days post partum (range 0-52, with higher scores indicating worse depression). Adverse events were monitored until 24 hours after childbirth. RESULTS: A total of 364 mothers (mean age 31.8 (standard deviation 4.1) years) were enrolled and randomised. At 42 days post partum, a major depressive episode was observed in 6.7% (12/180) of participants in the esketamine group compared with 25.4% (46/181) in the placebo group (relative risk 0.26, 95% confidence interval (CI) 0.14 to 0.48; P<0.001). Edinburgh postnatal depression scale scores were lower in the esketamine group at seven days (median difference -3, 95% CI -4 to -2; P<0.001) and 42 days (-3, -4 to -2; P<0.001). Hamilton depression rating scale scores at 42 days post partum were also lower in the esketamine group (-4, -6 to -3; P<0.001). The overall incidence of neuropsychiatric adverse events was higher in the esketamine group (45.1% (82/182) v 22.0% (40/182); P<0.001); however, symptoms lasted less than a day and none required drug treatment. CONCLUSIONS: For mothers with prenatal depression, a single low dose of esketamine after childbirth decreases major depressive episodes at 42 days post partum by about three quarters. Neuropsychiatric symptoms were more frequent but transient and did not require drug intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT04414943.
Assuntos
Depressão Pós-Parto , Ketamina , Humanos , Feminino , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Adulto , Método Duplo-Cego , Gravidez , Depressão Pós-Parto/tratamento farmacológico , Depressão Pós-Parto/prevenção & controle , Antidepressivos/administração & dosagem , Antidepressivos/uso terapêutico , Antidepressivos/efeitos adversos , Transtorno Depressivo Maior/tratamento farmacológico , Transtorno Depressivo Maior/prevenção & controle , China/epidemiologia , Resultado do Tratamento , Complicações na Gravidez/psicologia , Complicações na Gravidez/tratamento farmacológico , Escalas de Graduação Psiquiátrica , Mães/psicologiaRESUMO
KEY MESSAGE: ABI5 functions in ABA-mediated anthocyanin accumulation in plant response to low phosphate. Low phosphate (LP)-induced anthocyanin biosynthesis and accumulation play an important role in plant adaptive response to phosphate starvation conditions. However, whether and how the stress phytohormone abscisic acid (ABA) participates in LP-induced anthocyanin accumulation remain elusive. Here, we report that ABA is required for LP-induced anthocyanin accumulation in Arabidopsis thaliana. Disrupting ABA DEFICIENT2 (ABA2), a key ABA-biosynthetic gene, or BETA-GLUCOSIDASE1 (BG1), a major gene implicated in converting conjugated ABA to active ABA, significantly impairs LP-induced anthocyanin accumulation, as LP-induced expression of the anthocyanin-biosynthetic genes Chalcone Synthase (CHS) is dampened in the aba2 and bg1 mutant. In addition, LP-induced anthocyanin accumulation is defective in the mutants of ABA signaling pathway, including ABA receptors, ABA Insensitive2, and the transcription factors ABA Insensitive5 (ABI5), suggesting a role of ABI5 in ABA-mediated upregulation of anthocyanin-biosynthetic genes in plant response to LP. Indeed, LP-induced expression of CHS is repressed in the abi5-7 mutant but further promoted in the ABI5-overexpressing plants compared to the wild-type. Moreover, ABI5 can bind to and transcriptionally activate CHS, and the defectiveness of LP-induced anthocyanin accumulation in abi5-7 can be restored by overexpressing CHS. Collectively, our findings illustrates that ABI5 functions in ABA-mediated LP-induced anthocyanin accumulation in Arabidopsis.
Assuntos
Antocianinas , Proteínas de Arabidopsis , Arabidopsis , Fatores de Transcrição de Zíper de Leucina Básica , Ácido Abscísico/metabolismo , Antocianinas/metabolismo , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Fatores de Transcrição de Zíper de Leucina Básica/genética , Fatores de Transcrição de Zíper de Leucina Básica/metabolismo , Regulação da Expressão Gênica de Plantas , Germinação/genética , Sementes/genética , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Cold stress poses significant limitations on the growth, latex yield, and ecological distribution of rubber trees (Hevea brasiliensis). The GSK3-like kinase plays a significant role in helping plants adapt to different biotic and abiotic stresses. However, the functions of GSK3-like kinase BR-INSENSITIVE 2 (BIN2) in Hevea brasiliensis remain elusive. Here, we identified HbBIN2s of Hevea brasiliensis and deciphered their roles in cold stress resistance. The transcript levels of HbBIN2s are upregulated by cold stress. In addition, HbBIN2s are present in both the nucleus and cytoplasm and have the ability to interact with the INDUCER OF CBF EXPRESSION1(HbICE1) transcription factor, a central component in cold signaling. HbBIN2 overexpression in Arabidopsis displays decreased tolerance to chilling stress with a lower survival rate and proline content but a higher level of electrolyte leakage (EL) and malondialdehyde (MDA) than wild type under cold stress. Meanwhile, HbBIN2 transgenic Arabidopsis treated with cold stress exhibits a significant increase in the accumulation of reactive oxygen species (ROS) and a decrease in the activity of antioxidant enzymes. Further investigation reveals that HbBIN2 inhibits the transcriptional activity of HbICE1, thereby attenuating the expression of C-REPEAT BINDING FACTOR (HbCBF1). Consistent with this, overexpression of HbBIN2 represses the expression of CBF pathway cold-regulated genes under cold stress. In conclusion, our findings indicate that HbBIN2 functions as a suppressor of cold stress resistance by modulating HbICE1 transcriptional activity and ROS homeostasis.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Hevea , Hevea/genética , Hevea/metabolismo , Resposta ao Choque Frio/genética , Espécies Reativas de Oxigênio/metabolismo , Arabidopsis/genética , Arabidopsis/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Homeostase , Proteínas Quinases/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismoRESUMO
Maternal immune activation (MIA) during pregnancy is considered a risk factor for neurodevelopment in the offspring, resulting in behavioral abnormalities. Furthermore, adolescence is a vulnerable period for developing different psycho-cognitive deficits. Here, we aimed to observe the cognitive consequences of prenatal MIA exposure in adolescents and explored the underlying mechanisms. We divided dams into CON and MIA groups after inducing a mouse model of MIA using lipopolysaccharide (120 µg/kg) on gestational day 15. Open field (OF), elevated plus maze (EPM), and novel object recognition (NOR) tests were performed on postnatal day (PD) 35-37. The expression of hippocampal Wisteria floribunda agglutinin (WFA)+ perineuronal net (PNN), parvalbumin (PV), glial fibrillary acidic protein (GFAP), and ionized calcium-binding adapter molecule-1(Iba-1) were evaluated using immunofluorescence, and the expression of matrix metalloprotein-9 (MMP-9) in the hippocampus was assessed using the western blot. Following the infusion of chondroitinase ABC (ChABC) into CA1 in the offspring from the CON group on PD 30, they were divided into ChABC and Sham groups. OF, EPM, and NOR were performed on PD 35-37. Compared to the CON group, decreased exploration time of the novel object and preference ratio were observed in the MIA group. Meanwhile, the MIA group presented significantly decreased WFA+ PNN in CA1, increased Iba-1+ microglia, and MMP-9 in the hippocampus. Additionally, the density of PV+ neurons and GFAP+ astrocytes was comparable between both groups. After digesting the PNN, the exploration time of novel object and preference ratio decreased in the ChABC group compared to the Sham group. Conclusively, the PNN deficit in CA1 caused by prenatal MIA might, at least partially, induce cognitive impairment in adolescents. Microglia and MMP-9 may also be potential candidates for PNN deficit after MIA.
Assuntos
Disfunção Cognitiva , Metaloproteinase 9 da Matriz , Animais , Feminino , Hipocampo , Camundongos , Microglia , Parvalbuminas , GravidezRESUMO
Magnesium (Mg) is an essential metal for chlorophyll biosynthesis and other metabolic processes in plant cells. Mg is largely stored in the vacuole of various cell types and remobilized to meet cytoplasmic demand. However, the transport proteins responsible for mobilizing vacuolar Mg2+ remain unknown. Here, we identified two Arabidopsis (Arabidopsis thaliana) Mg2+ transporters (MAGNESIUM TRANSPORTER 1 and 2; MGT1 and MGT2) that facilitate Mg2+ mobilization from the vacuole, especially when external Mg supply is limited. In addition to a high degree of sequence similarity, MGT1 and MGT2 exhibited overlapping expression patterns in Arabidopsis tissues, implying functional redundancy. Indeed, the mgt1 mgt2 double mutant, but not mgt1 and mgt2 single mutants, showed exaggerated growth defects as compared to the wild type under low-Mg conditions, in accord with higher expression levels of Mg-starvation gene markers in the double mutant. However, overall Mg level was also higher in mgt1 mgt2, suggesting a defect in Mg2+ remobilization in response to Mg deficiency. Consistently, MGT1 and MGT2 localized to the tonoplast and rescued the yeast (Saccharomyces cerevisiae) mnr2Δ (manganese resistance 2) mutant strain lacking the vacuolar Mg2+ efflux transporter. In addition, disruption of MGT1 and MGT2 suppressed high-Mg sensitivity of calcineurin B-like 2 and 3 (cbl2 cbl3), a mutant defective in vacuolar Mg2+ sequestration, suggesting that vacuolar Mg2+ influx and efflux processes are antagonistic in a physiological context. We further crossed mgt1 mgt2 with mgt6, which lacks a plasma membrane MGT member involved in Mg2+ uptake, and found that the triple mutant was more sensitive to low-Mg conditions than either mgt1 mgt2 or mgt6. Hence, Mg2+ uptake (via MGT6) and vacuolar remobilization (through MGT1 and MGT2) work synergistically to achieve Mg2+ homeostasis in plants, especially under low-Mg supply in the environment.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Deficiência de Magnésio , Aclimatação , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Calcineurina/genética , Proteínas de Transporte/metabolismo , Clorofila/metabolismo , Regulação da Expressão Gênica de Plantas , Humanos , Magnésio/metabolismo , Deficiência de Magnésio/metabolismo , Manganês/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Saccharomyces cerevisiae/metabolismo , Vacúolos/metabolismoRESUMO
H2O2 affects the expression of genes that are involved in plant responses to diverse environmental stresses; however, the underlying mechanisms remain elusive. Here, we demonstrate that H2O2 enhances plant freezing tolerance through its effect on a protein product of low expression of osmotically responsive genes2 (LOS2). LOS2 is translated into a major product, cytosolic enolase2 (ENO2), and sometimes an alternative product, the transcription repressor c-Myc-binding protein (MBP-1). ENO2, but not MBP-1, promotes cold tolerance by binding the promoter of C-repeat/DRE binding factor1 (CBF1), a central transcription factor in plant cold signaling, thus activating its expression. Overexpression of CBF1 restores freezing sensitivity of a LOS2 loss-of-function mutant. Furthermore, cold-induced H2O2 increases nuclear import and transcriptional binding activity of ENO2 by sulfenylating cysteine 408 and thereby promotes its oligomerization. Collectively, our results illustrate how H2O2 activates plant cold responses by sulfenylating ENO2 and promoting its oligomerization, leading to enhanced nuclear translocation and transcriptional activation of CBF1.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Proteínas de Arabidopsis/metabolismo , Temperatura Baixa , Congelamento , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/farmacologia , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
Low temperature is a key factor limiting the rubber plantation extending to high latitude area. Previous work has shown that cold-induced DNA demethylation was coordinated with the expression of cold-responsive (COR) genes in Hevea brasiliensis. In this work, reduced representation bisulphite sequencing analysis of H. brasiliensis showed that cold treatment induced global genomic DNA demethylation and altered the sequence contexts of methylated cytosines, but the levels of mCG methylation in transposable elements were slightly enhanced by cold treatment. Integrated analysis of the DNA methylome and transcriptome revealed 400 genes whose expression correlated with altered DNA methylation. DNA demethylation in the upstream region of gene seems to correlate with higher gene expression, whereas demethylation in the gene body has less association. Our results suggest that cold treatment globally change the genomic DNA methylation status of the rubber tree, which might coordinate reprogramming of the transcriptome.
RESUMO
Low temperature remarkably limits rubber tree (Hevea brasiliensis Muell. Arg.) growth, latex production, and geographical distribution, but the underlying mechanisms of Hevea brasiliensis cold stress response remain elusive. Here, we identified HbSnRK2.6 as a key component in ABA signaling functions in phytohormone abscisic acid (ABA)-regulated cold stress response in Hevea brasiliensis. Exogenous application of ABA enhances Hevea brasiliensis cold tolerance. Cold-regulated (COR) genes in the CBF pathway are upregulated by ABA. Transcript levels of all five HbSnRK2.6 members are significantly induced by cold, while HbSnRK2.6A, HbSnRK2.6B, and HbSnRK2.6C can be further activated by ABA under cold conditions. Additionally, HbSnRK2.6s are localized in the cytoplasm and nucleus, and can physically interact with HbICE2, a crucial positive regulator in the cold signaling pathway. Overexpression of HbSnRK2.6A or HbSnRK2.6B in Arabidopsis extensively enhances plant responses to ABA and expression of COR genes, leading to increased cold stress tolerance. Furthermore, HbSnRK2.6A and HbSnRK2.6B can promote transcriptional activity of HbICE2, thus, increasing the expression of HbCBF1. Taken together, we demonstrate that HbSnRK2.6s are involved in ABA-regulated cold stress response in Hevea brasiliensis by regulating transcriptional activity of HbICE2.
Assuntos
Ácido Abscísico/farmacologia , Resposta ao Choque Frio , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Hevea/metabolismo , Proteínas de Plantas/metabolismo , Proteínas Quinases/metabolismo , Fatores de Transcrição/metabolismo , Hevea/efeitos dos fármacos , Hevea/genética , Reguladores de Crescimento de Plantas/farmacologia , Proteínas de Plantas/genética , Proteínas Quinases/genética , Fatores de Transcrição/genéticaRESUMO
Salicylic acid (SA) acts antagonistically to jasmonic acid (JA) in plant immunity. We previously reported that CATALASE2 (CAT2) promotes JA-biosynthetic acyl-CoA oxidase (ACX) activity to enhance plant resistance to necrotrophic Botrytis cinerea, and SA represses JA biosynthesis through inhibiting CAT2 activity, while the underlying mechanism remains to be further elucidated. Here, we report that the truncated CAT2 N-terminus (CAT2-N) interacts with and promotes ACX2/3, and CAT2-N-overexpressing plants have increased JA accumulation and enhanced resistance to B. cinerea B05.10, but compromised antagonism of SA on JA. Catalase inhibitor treatment or mutating CAT2 active amino acids abolished CAT2 H2 O2 -decomposing activity but did not affect its promotion of ACX2/3 activity via interaction. CAT2-N, a truncated protein with no catalase activity, interacted with and promoted ACX2/3. Overexpressing CAT2-N in Arabidopsis plants resulted in increased ACX activity, higher JA accumulation, and stronger resistance to B. cinerea B05.10 infection. Additionally, SA dramatically repressed JA biosynthesis and resistance to B. cinerea in the wild type but not in the CAT2-N-overexpressing plants. Together, our study reveals that CAT2-N can be utilized as an accelerator for JA biosynthesis during plant resistance to B. cinerea B05.10, and this truncated protein partly relieves SA repression of JA biosynthesis in plant defence responses.
Assuntos
Proteínas de Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Botrytis/metabolismo , Ciclopentanos , Regulação da Expressão Gênica de Plantas , Oxilipinas , Doenças das Plantas , Ácido SalicílicoRESUMO
Transthoracic echocardiographic evaluation of the right ventricle is more difficult than the left ventricle and has not been well characterised in the parturient during delivery. As a preliminary investigation, our goal was to use bedside transthoracic echocardiography to evaluate right ventricular myocardial function before and after caesarean delivery. Term parturients undergoing caesarean delivery under spinal anaesthesia were enrolled. Echocardiography was performed pre- and postoperatively. Assessment of myocardial function included longitudinal myocardial strain using 2D-speckle tracking for both ventricles, and fractional area change for the right ventricle. Troponin-T, creatine kinase-muscle/brain and brain natriuretic peptide were measured pre- and postoperatively. One hundred patients were enrolled; 98 completed the study. Adequate images from both timepoints (pre- and postoperatively) were obtained in 85 patients for left ventricle assessment, and 66 for the right ventricle. Right ventricular fractional area change (mean (standard deviation)) (24.9% (8.9%) to 24.9% (9.2%); P = 0.99) and strain (-19.7% (6.8%) to -18.1% (6.5%); P = 0.08) measurements suggested mild baseline dysfunction and did not change after delivery. Left ventricular strain values were normal and unchanged after delivery (-23.8% (7.4%) to -24.3% (6.7%); P = 0.51). One patient had elevated troponin-T and demonstrated worse biventricular function. Elevation of brain natriuretic peptide (n=7) was associated with mildly decreased left ventricular strain, but creatine kinase-muscle/brain (n=4) was not associated with consistent changes in cardiac function. Further investigations into peripartum right ventricular function are required to validate the findings in this preliminary study. Findings of baseline mild right ventricular dysfunction and functional changes associated with troponin-T and brain natriuretic peptide warrant rigorous investigation.
Assuntos
Cesárea , Ventrículos do Coração , Disfunção Ventricular Direita , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Gravidez , Disfunção Ventricular Direita/diagnóstico , Função Ventricular DireitaRESUMO
Sepsis-associated encephalopathy (SAE) is a potentially irreversible acute cognitive dysfunction with unclear mechanism. Striatal-enriched protein tyrosine phosphatase (STEP) is a brain-specific phosphatase which normally opposes synaptic strengthening by regulating key signaling molecules involved in synaptic plasticity and neuronal function. Thus, we hypothesized that abnormal STEP signaling pathway was involved in sepsis-induced cognitive impairment evoked by lipopolysaccharides (LPS) injection. The levels of STEP, phosphorylation of GluN2B (pGluN2B), the kinases extracellular signal-regulated kinase 1/2 (pERK), cAMP-response element binding protein (CREB), synaptophysin, brain derived neurotrophic factor (BDNF), and post-synaptic density protein 95 (PSD95) in the hippocampus, prefrontal cortex, and striatum were determined at the indicated time points. In the present study, we found that STEP levels were significantly increased in the hippocampus, prefrontal cortex, and striatum following LPS injection, which might resulted from the disruption of the ubiquitin-proteasome system. Notably, a STEP inhibitor TC-2153 treatment alleviated sepsis-induced memory impairment by increasing phosphorylation of GluN2B and ERK1/2, CREB/BDNF, and PSD95. In summary, our results support the key role of STEP in sepsis-induced memory impairment in a mouse model of SAE, whereas inhibition of STEP may provide a novel therapeutic approach for this disorder and possible other neurodegenerative diseases.
Assuntos
Transtornos da Memória/fisiopatologia , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Encefalopatia Associada a Sepse/fisiopatologia , Transdução de Sinais/fisiologia , Animais , Benzotiepinas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/química , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Corpo Estriado/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/química , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Proteína 4 Homóloga a Disks-Large/química , Proteína 4 Homóloga a Disks-Large/metabolismo , Hipocampo/metabolismo , Lipopolissacarídeos , Masculino , Memória/efeitos dos fármacos , Memória/fisiologia , Transtornos da Memória/induzido quimicamente , Camundongos Endogâmicos C57BL , Proteína Quinase 1 Ativada por Mitógeno/química , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/química , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fosforilação/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo , Encefalopatia Associada a Sepse/induzido quimicamente , Transdução de Sinais/efeitos dos fármacosRESUMO
KEY MESSAGE: An ICE-like transcription factor mediates jasmonate-regulated cold tolerance in the rubber tree (Hevea brasiliensis), and confers cold tolerance in transgenic Arabidopsis. The rubber tree (Hevea brasiliensis) is susceptible to low temperatures, and understanding the mechanisms regulating cold stress is of great potential value for enhancing tolerance to this environmental variable. In this study, we find that treatment with exogenous methyl jasmonate (MeJA) could significantly enhance Hevea brasiliensis cold tolerance. In addition, yeast two-hybrid and bimolecular fluorescence complementation (BiFC) experiments show that JASMONATE ZIM-DOMAIN(JAZ) proteins, HbJAZ1 and HbJAZ12, key repressors of JA signaling pathway, interact with HbICE2, a novel ICE (Inducer of CBF Expression)-like protein. HbICE2 was nuclear-localised and bound to the MYC recognition (MYCR) sequence. The transcriptional activation activity of HbICE2 in yeast cells was dependent on the N-terminus, and overexpression of HbICE2 in Arabidopsis resulted in elevated tolerance to chilling stress. Furthermore, dual-luciferase transient assay reveals that HbJAZ1 and HbJAZ12 proteins inhibit the transcriptional function of HbICE2. The expression of C-repeat-binding factor (CBF) signalling pathway genes including HbCBF1, HbCBF2 and HbCOR47 were up-regulated by MeJA. Taken together, our data suggest that the new ICE-like transcription factor HbICE2 is involved in jasmonate-regulated cold tolerance in Hevea brasiliensis.
Assuntos
Ciclopentanos/farmacologia , Hevea/efeitos dos fármacos , Hevea/metabolismo , Oxilipinas/farmacologia , Proteínas de Plantas/metabolismo , Fatores de Transcrição/metabolismo , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/genética , Hevea/genética , Proteínas de Plantas/genética , Fatores de Transcrição/genéticaRESUMO
Brain dysfunction remains a common complication after sepsis development and is an independent risk factor for a poorer prognosis and an increased mortality. Here we tested the hypothesis that the behavioral outcomes after lipopolysaccharides (LPS) administration are exacerbated by an impoverished environment (IE) and alleviated by an enriched environment (EE), respectively. Mice were randomly allocated in a standard environment (SE), an EE, or an IE for 4 weeks after LPS or normal saline (NS) administration. Neurobehavioral alternations were assessed by the open field, novel objective recognition, and fear conditioning tests. The expressions of proinflammatory cytokines (tumor necrosis factor (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-10), ionized calcium-binding adaptor molecule-1 (IBA1)-positive cells as well as glial fibrillary acidic protein (GFAP)-positive cells, brain derived neurotrophic factor (BDNF), 5-bromo-2-deoxyuridine-labeled cells in the dentate gyrus of the hippocampus, and the number of dendritic spines in the hippocampal CA1 were determined. Our results showed that the some of the neurocognitive abnormalities induced by LPS administration can be aggravated by stressful conditions such as IE but alleviated by EE. These neurocognitive alternations were accompanied by significant changes in biomarkers of immune response and hippocampal synaptic plasticity. In summary, our study confirmed the negative impact of IE and the positive effects of EE on the cognitive function after LPS administration, with potential implications to the basis of sepsis-related cognitive impairments in the critically ill patients.
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Rubber trees (Hevea brasiliensis) were successfully introduced to south China in the 1950s on a large-scale; however, due to the climate, are prone to cold injury during the winter season. Increased cold tolerance is therefore an important goal, yet the mechanism underlying rubber tree responses to cold stress remains unclear. This study carried out functional characterization of HbICE1 (Inducer of CBF Expression 1) from H. brasiliensis. A nucleic protein with typical features of ICEs, HbICE1 was able to bind to MYC recognition sites and had strong transactivation activity. HbICE1 was constitutively expressed in all tested tissues, with highest levels in the bark, and was up-regulated when subjected to various stresses including cold, dehydration, salinity and wounding. When overexpressed in Arabidopsis, 35S::HbICE1 plants showed enhanced cold resistance with increased proline content, reduced malondialdehyde (MDA) metabolism and electrolyte leakage, and decreased reactive oxygen species (ROS) accumulation. Expression of the cold responsive genes (COR15A, COR47, RD29A, and KIN1) was also significantly promoted in 35S::HbICE1 compared to wild-type plants under cold stress. Differentially expressed genes (DEGs) analysis showed that cold treatment changed genes expression profiles involved in many biological processes and phytohormones perception and transduction. Ethylene, JA, ABA, as well as ICE-CBF signaling pathways might work synergistically to cope with cold tolerance in rubber tree. Taken together, these findings suggest that HbICE1 is a member of the ICE gene family and a positive regulator of cold tolerance in H. brasiliensis.
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Increased fatty acid ß-oxidation is essential for early postgerminative growth in seedlings, but high levels of H2 O2 produced by ß-oxidation can induce oxidative stress. Whether and how catalase (CAT) functions in fine-tuning H2 O2 homeostasis during seedling growth remain unclear. Here, we report that CAT2 functions in early seedling growth. Compared to the wild type, the cat2-1 mutant, with elevated H2 O2 levels, exhibited reduced root elongation on sucrose (Suc)-free medium, mimicking soils without exogenous sugar supply. Treatment with the H2 O2 scavenger potassium iodide rescued the mutant phenotype of cat2-1. In contrast to the wild type, the cat2-1 mutant was insensitive to the CAT inhibitor 3-amino-1,2,4-triazole in terms of root elongation when grown on Suc-free medium, suggesting that CAT2 modulates early seedling growth by altering H2 O2 accumulation. Furthermore, like cat2-1, the acyl-CoA oxidase (ACX) double mutant acx2-1 acx3-6 showed repressed root elongation, suggesting that CAT2 functions in early seedling growth by regulating ACX activity, as this activity was inhibited in cat2-1. Indeed, decreased ACX activity and short root of cat2-1 seedlings grown on Suc-free medium were rescued by overexpressing ACX3. Together, these findings suggest that CAT2 functions in early seedling growth by scavenging H2 O2 and stimulating ACX2/3 activity.
Assuntos
Acil-CoA Oxidase/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/crescimento & desenvolvimento , Sequestradores de Radicais Livres/metabolismo , Germinação , Peróxido de Hidrogênio/metabolismo , Plântula/crescimento & desenvolvimento , Ácido 2,4-Diclorofenoxiacético/análogos & derivados , Ácido 2,4-Diclorofenoxiacético/farmacologia , Amitrol (Herbicida)/farmacologia , Arabidopsis/efeitos dos fármacos , Arabidopsis/enzimologia , Arabidopsis/genética , Germinação/efeitos dos fármacos , Mutação/genética , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Iodeto de Potássio/farmacologia , Plântula/efeitos dos fármacos , SacaroseRESUMO
Plants defend against pathogen attack by modulating auxin signaling and activating the salicylic acid (SA) and jasmonic acid (JA) signaling pathways. SA and JA act antagonistically in resistance to specific pathogen types, yet how plants coordinate these phytohormones remains elusive. Here we report that biotrophic-pathogen-induced SA accumulation dampens both auxin and JA synthesis by inhibiting CATALASE2 (CAT2) activity in the model plant Arabidopsis. SA suppression of CAT2 results in increased H2O2 levels and subsequent sulfenylation of tryptophan synthetase ß subunit 1, thus depleting the auxin biosynthetic precursor tryptophan. In addition, we find that CAT2 promotes JA biosynthesis by facilitating direct interaction of the JA biosynthetic enzymes ACX2 and ACX3, and thus SA repression of CAT2 inhibits JA accumulation. As such, the cat2-1 mutant exhibits increased resistance to biotrophic pathogens and increased susceptibility to necrotrophic pathogens. Our study illustrates how CAT2 coordinates SA repression of auxin accumulation and JA biosynthesis in plant defense.
Assuntos
Acil-CoA Oxidase/metabolismo , Proteínas de Arabidopsis/metabolismo , Catalase/metabolismo , Ciclopentanos/metabolismo , Ácidos Indolacéticos/metabolismo , Oxilipinas/metabolismo , Ácido Salicílico/metabolismo , Acil-CoA Oxidase/genética , Arabidopsis/enzimologia , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Catalase/antagonistas & inibidores , Catalase/genética , Regulação da Expressão Gênica de Plantas , Peróxido de Hidrogênio/metabolismo , Reguladores de Crescimento de Plantas/metabolismo , Transdução de SinaisRESUMO
Nitric oxide (NO) generation by NO synthase (NOS) in guard cells plays a vital role in stomatal closure for adaptive plant response to drought stress. However, the mechanism underlying the regulation of NOS activity in plants is unclear. Here, by screening yeast deletion mutants with decreased NO accumulation and NOS-like activity when subjected to H2 O2 stress, we identified TUP1 as a novel regulator of NOS-like activity in yeast. Arabidopsis WD40-REPEAT 5a (WDR5a), a homolog of yeast TUP1, complemented H2 O2 -induced NO accumulation of a yeast mutant Δtup1, suggesting the conserved role of WDR5a in regulating NO accumulation and NOS-like activity. This note was further confirmed by using an Arabidopsis RNAi line wdr5a-1 and two T-DNA insertion mutants of WDR5a with reduced WDR5a expression, in which both H2 O2 -induced NO accumulation and stomatal closure were repressed. This was because H2 O2 -induced NOS-like activity was inhibited in the mutants compared with that of the wild type. Furthermore, these wdr5a mutants were more sensitive to drought stress as they had reduced stomatal closure and decreased expression of drought-related genes. Together, our results revealed that WDR5a functions as a novel factor to modulate NOS-like activity for changes of NO accumulation and stomatal closure in drought stress tolerance.
Assuntos
Adaptação Fisiológica , Proteínas de Arabidopsis/metabolismo , Arabidopsis/fisiologia , Proteínas de Transporte/metabolismo , Secas , Óxido Nítrico/metabolismo , Estresse Fisiológico , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Apoptose/efeitos dos fármacos , Arabidopsis/efeitos dos fármacos , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Transporte/genética , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Genes de Plantas , Peróxido de Hidrogênio/farmacologia , Óxido Nítrico Sintase/metabolismo , Estômatos de Plantas/efeitos dos fármacos , Estômatos de Plantas/fisiologia , Saccharomyces cerevisiae/metabolismo , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genéticaRESUMO
[This corrects the article on p. 825 in vol. 7, PMID: 27379121.].
RESUMO
Pollen tubes are an ideal model for the study of cell growth and morphogenesis because of their extreme elongation without cell division; however, the genetic basis of pollen germination and tube growth remains largely unknown. Using the Illumina/Solexa digital gene expression system, we identified 13,017 genes (representing 28.3% of the unigenes on the reference genes) at three stages, including mature pollen, hydrated pollen, and pollen tubes of Populus simonii × P. nigra. Comprehensive analysis of P. simonii × P. nigra pollen revealed dynamic changes in the transcriptome during pollen germination and pollen tube growth (PTG). Gene ontology analysis of differentially expressed genes showed that genes involved in functional categories such as catalytic activity, binding, transporter activity, and enzyme regulator activity were overrepresented during pollen germination and PTG. Some highly dynamic genes involved in pollen germination and PTG were detected by clustering analysis. Genes related to some key pathways such as the mitogen-activated protein kinase signaling pathway, regulation of the actin cytoskeleton, calcium signaling, and ubiquitin-mediated proteolysis were significantly changed during pollen germination and PTG. These data provide comprehensive molecular information toward further understanding molecular mechanisms underlying pollen germination and PTG.
RESUMO
The root is the first plant organ to get in contact with the toxin cadmium (Cd), which is a widespread soil contaminant. Cd inhibits the growth of the primary root, but the mechanisms underlying this inhibition remain elusive. In this study, we used physiological, pharmacological and genetic approaches to investigate the roles of nitric oxide (NO) and auxin in Cd-mediated inhibition of Arabidopsis thaliana root meristem growth. Our study demonstrated that in the first 12 h of exposure, Cd inhibits primary root elongation through a decrease in the sizes of both the elongation and meristematic zones. Following Cd exposure, a decrease in auxin levels is associated with reduced PIN1/3/7 protein accumulation, but not with reduced PIN1/3/7 transcript levels. Additionally, Cd stabilized AXR3/IAA17 protein to repress auxin signalling in this Cd-mediated process. Furthermore, decreasing Cd-induced NO accumulation with either NO-specific scavenger 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO) or NO synthase inhibitor N(ω) -nitro-l-Arg-methylester (l-NAME) compromised the Cd-mediated inhibition of root meristem development, reduction in auxin and PIN1/3/7 accumulation, as well as stabilization of AXR3/IAA17, indicating that NO participates in Cd-mediated inhibition of root meristem growth. Taken together, our data suggest that Cd inhibits root meristem growth by NO-mediated repression of auxin accumulation and signalling in Arabidopsis.