scholarly journals Effect of the host-specific toxin SnTOX3 from Stagonospora nodorum on ethylene signaling pathway regulation and redox-state in common wheat

2019 ◽  
Vol 23 (7) ◽  
pp. 856-864 ◽  
Author(s):  
S. V. Veselova ◽  
G. F. Burkhanova ◽  
T. V. Nuzhnaya ◽  
S. D. Rumyantsev ◽  
I. V. Maksimov
Keyword(s):  
Signaling Pathway ◽  
Redox State ◽  
Molecular Mechanisms ◽  
Activity Patterns ◽  
Ethylene Biosynthesis ◽  
Host Susceptibility ◽  
Stagonospora Nodorum ◽  
Redox Metabolism ◽  
Ethylene Biosynthesis And Signaling ◽  
Gene For Gene

The fungus Stagonospora nodorum Berk. is the causative agent of Septoria nodorum blotch (SNB) of wheat. The most important factors of Stagonospora nodorum virulence include numerous fungal necrotrophic effectors (NEs) encoded by SnTox genes. They interact with the matching products of host susceptibility genes (Snn). SnTox-Snn interactions are mirror images of classical gene-for-gene interactions and lead to the development of disease. We have studied the SnTox3-Snn3 interaction, resulting in the development of infection on leaves and formation of extensive lesions. The mechanism of SnTox3 action is likely to be linked to the regulation of redox metabolism and the influence on ethylene synthesis in the wheat plants, although the molecular mechanisms are not fully unveiled. To characterize the SnTox3-Snn3 interaction, we used S. nodorum isolates differing in the expression of the NEs genes SnTox3 (SnB (Tox3+), Sn4VD (Tox3–)) and two soft spring wheat (Triticum aestivum L.) cultivars, contrasting in resistance to the SNB agent and differing in the allelic composition of the susceptibility locus Snn3-B1: Kazakhstanskaya 10 (susceptible) and Omskaya 35 (resistant). We carried out a comparative assessment of the transcriptional activity patterns of genes responsible for ethylene biosynthesis (TaACS1, TaACО) and signaling pathway (TaEIL1, TaERF1) by real-time PCR and estimated the redox state of wheat plants infected with different isolates of S. nodorum by spectrometry. The induction of ethylene biosynthesis and signaling has been shown to result from gene-for-gene interaction between Snn3-B1 and SnTox3. The results of plant redox status estimation showed that ethylene inhibited accumulation of hydrogen peroxide in SnTox3-sensitive genotypes by regulating the operation of various pro-/antioxidant enzymes at the transcriptional and posttranslational levels. Our results suggest that NE SnTox3 influences ethylene biosynthesis and signaling, thereby regulating redox metabolism in infected wheat plants as necessary for successful host colonization at the initial phases of infection, which ultimately leads to extensive lesions due to fast pathogen reproduction.

Effect of SnTOX effectors on the virulence degree of Stagonospora nodorum isolates

Biomics ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 343-351
Author(s):  
S.V. Veselova ◽  
G.F. Burkhanova ◽  
S.D. Rumyantsev ◽  
T.V. Nuzhnaya
Keyword(s):  
Host Plant ◽  
Transcriptional Activity ◽  
Susceptibility Gene ◽  
Stagonospora Nodorum ◽  
Quantitative Composition ◽  
Host Genotype ◽  
Mrna Accumulation ◽  
Gene System ◽  
Compatible Interactions ◽  
Gene For Gene

Stagonospora nodorum Berk. is the causal agent of Septoria nodorum blotch (SNB) of wheat (Triticum aestivum L.). It synthesizes host-specific necrotrophic effectors (NEs), which facilitate infection process and ensure virulence of pathogen on host plant with a dominant susceptibility gene. The interaction of virulence genes products of the NEs pathogen (SnTox) with susceptibility genes products of the host plant (Snn) in the S. nodorum - wheat pathosystem is carried out in inverted gene-for-gene system and causes the development of disease. In this study, we tested three main NEs SnToxA, SnTox1, SnTox3, which have already been identified in S. nodorum at the gene level. The NEs role in the development of SNB has already been proven; however, the overall host response to SNB does not always strictly follow the inverted gene-for-gene system, as multiple SnTox-Snn interactions can be additive or epistatic. In this regard, the aim of the work was to identify the NE genes in three S. nodorum isolates and to study effect of NEs genes transcriptional activity on the isolate virulence. We have shown that all three NEs SnToxA, SnTox3 and SnTox1 played an important role in the development of the disease in compatible interactions. Effectors SnTox3 and SnTox1 exhibited epistatic interaction that was removed by a triple compatible interaction (SnTox3-Snn3, SnToxA-Tsn1 and SnTox1-Snn1). This effect was shown by us for the first time. The mechanisms of epistatic and additive interactions, as well as the virulence of the isolate were associated with the regulation of the NEs genes transcriptional activity. The avirulent isolate Sn4VD lacked transcription of all three NEs genes, and the virulent isolate Sn9MH was characterized by a high level of mRNA accumulation of all three NEs genes during infection on susceptible cultivar. We also showed that SnTox expression depended both on the host genotype in SnToxA and SnTox3 and on the number of compatible interactions exhibiting additive or epistatic interactions in SnTox1 and SnTox3. Finally, the virulence of the S. nodorum isolate depended on the qualitative and quantitative composition of NEs.

Pisosterol Induces G2/M Cell Cycle Arrest and Apoptosis via the ATM/ATR Signaling Pathway in Human Glioma Cells

2020 ◽  
Vol 20 (6) ◽  
pp. 734-750
Author(s):  
Wallax A.S. Ferreira ◽  
Rommel R. Burbano ◽  
Claudia do Ó. Pessoa ◽  
Maria L. Harada ◽  
Bárbara do Nascimento Borges ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Signaling Pathway ◽  
Glioma Cell ◽  
Molecular Mechanisms ◽  
Glioma Cells ◽  
Dependent Manner ◽  
M Cell ◽  
Trypan Blue Exclusion ◽  
Cycle Arrest

Background: Pisosterol, a triterpene derived from Pisolithus tinctorius, exhibits potential antitumor activity in various malignancies. However, the molecular mechanisms that mediate the pisosterol-specific effects on glioma cells remain unknown. Objective: This study aimed to evaluate the antitumoral effects of pisosterol on glioma cell lines. Methods: The 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue exclusion assays were used to evaluate the effect of pisosterol on cell proliferation and viability in glioma cells. The effect of pisosterol on the distribution of the cells in the cell cycle was performed by flow cytometry. The expression and methylation pattern of the promoter region of MYC, ATM, BCL2, BMI1, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, MDM2, p14ARF and TP53 was analyzed by RT-qPCR, western blotting and bisulfite sequencing PCR (BSP-PCR). Results: Here, it has been reported that pisosterol markedly induced G2/M arrest and apoptosis and decreased the cell viability and proliferation potential of glioma cells in a dose-dependent manner by increasing the expression of ATM, CASP3, CDK1, CDKN1A, CDKN2A, CDKN2B, CHEK1, p14ARF and TP53 and decreasing the expression of MYC, BCL2, BMI1 and MDM2. Pisosterol also triggered both caspase-independent and caspase-dependent apoptotic pathways by regulating the expression of Bcl-2 and activating caspase-3 and p53. Conclusions: It has been, for the first time, confirmed that the ATM/ATR signaling pathway is a critical mechanism for G2/M arrest in pisosterol-induced glioma cell cycle arrest and suggests that this compound might be a promising anticancer candidate for further investigation.

scholarly journals A systems biology model of junctional localization and downstream signaling of the Ang–Tie signaling pathway

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yu Zhang ◽  
Christopher D. Kontos ◽  
Brian H. Annex ◽  
Aleksander S. Popel
Keyword(s):  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Reaction Network ◽  
Vascular Growth ◽  
Downstream Signaling ◽  
Signaling Axis ◽  
Agonistic Activity ◽  
Molecular Regulatory Mechanisms

AbstractThe Ang–Tie signaling pathway is an important vascular signaling pathway regulating vascular growth and stability. Dysregulation in the pathway is associated with vascular dysfunction and numerous diseases that involve abnormal vascular permeability and endothelial cell inflammation. The understanding of the molecular mechanisms of the Ang–Tie pathway has been limited due to the complex reaction network formed by the ligands, receptors, and molecular regulatory mechanisms. In this study, we developed a mechanistic computational model of the Ang–Tie signaling pathway validated against experimental data. The model captures and reproduces the experimentally observed junctional localization and downstream signaling of the Ang–Tie signaling axis, as well as the time-dependent role of receptor Tie1. The model predicts that Tie1 modulates Tie2’s response to the context-dependent agonist Ang2 by junctional interactions. Furthermore, modulation of Tie1’s junctional localization, inhibition of Tie2 extracellular domain cleavage, and inhibition of VE-PTP are identified as potential molecular strategies for potentiating Ang2’s agonistic activity and rescuing Tie2 signaling in inflammatory endothelial cells.

scholarly journals Mycobacterium tuberculosis Infection Up-Regulates Sialyl Lewis X Expression in the Lung Epithelium

2021 ◽  
Vol 9 (1) ◽  
pp. 99
Author(s):  
Rita Matos ◽  
Kaori L. Fonseca ◽  
Stefan Mereiter ◽  
Ana Raquel Maceiras ◽  
Joana Gomes ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Biosynthetic Pathway ◽  
Molecular Mechanisms ◽  
Tuberculosis Infection ◽  
Host Susceptibility ◽  
Sialyl Lewis X ◽  
Lung Pathology ◽  
Lung Epithelium ◽  
Lewis X ◽  
Sialyl Lewis

Glycans display increasingly recognized roles in pathological contexts, however, their impact in the host-pathogen interplay in many infectious diseases remains largely unknown. This is the case for tuberculosis (TB), one of the ten most fatal diseases worldwide, caused by infection of the bacteria Mycobacterium tuberculosis. We have recently reported that perturbing the core-2 O-glycans biosynthetic pathway increases the host susceptibility to M. tuberculosis infection, by disrupting the neutrophil homeostasis and enhancing lung pathology. In the present study, we show an increased expression of the sialylated glycan structure Sialyl-Lewis X (SLeX) in the lung epithelium upon M. tuberculosis infection. This increase in SLeX glycan epitope is accompanied by an altered lung tissue transcriptomic signature, with up-regulation of genes codifying enzymes that are involved in the SLeX core-2 O-glycans biosynthetic pathway. This study provides novel insights into previously unappreciated molecular mechanisms involving glycosylation, which modulate the host response to M. tuberculosis infection, possibly contributing to shape TB disease outcome.

scholarly journals DNA methylation mediated RSPO2 to promote follicular development in mammals

2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Xiaofeng Zhou ◽  
Yingting He ◽  
Nian Li ◽  
Guofeng Bai ◽  
Xiangchun Pan ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Wnt Signaling ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Molecular Mechanisms ◽  
Cpg Island ◽  
Wnt Signaling Pathway ◽  
Follicular Development ◽  
Expression Level

AbstractIn female mammals, the proliferation, apoptosis, and estradiol-17β (E2) secretion of granulosa cells (GCs) have come to decide the fate of follicles. DNA methylation and RSPO2 gene of Wnt signaling pathway have been reported to involve in the survival of GCs and follicular development. However, the molecular mechanisms for how DNA methylation regulates the expression of RSPO2 and participates in the follicular development are not clear. In this study, we found that the mRNA and protein levels of RSPO2 significantly increased during follicular development, but the DNA methylation level of RSPO2 promoter decreased gradually. Inhibition of DNA methylation or DNMT1 knockdown could decrease the methylation level of CpG island (CGI) in RSPO2 promoter and upregulate the expression level of RSPO2 in porcine GCs. The hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of transcription factor E2F1 and promoted the transcriptional activity of RSPO2. Moreover, RSPO2 promoted the proliferation of GCs with increasing the expression level of PCNA, CDK1, and CCND1 and promoted the E2 secretion of GCs with increasing the expression level of CYP19A1 and HSD17B1 and inhibited the apoptosis of GCs with decreasing the expression level of Caspase3, cleaved Caspase3, cleaved Caspase8, cleaved Caspase9, cleaved PARP, and BAX. In addition, RSPO2 knockdown promoted the apoptosis of GCs, blocked the development of follicles, and delayed the onset of puberty with decreasing the expression level of Wnt signaling pathway-related genes (LGR4 and CTNNB1) in vivo. Taken together, the hypomethylation of −758/−749 and −563/−553 regions in RSPO2 promoter facilitated the occupancy of E2F1 and enhanced the transcription of RSPO2, which further promoted the proliferation and E2 secretion of GCs, inhibited the apoptosis of GCs, and ultimately ameliorated the development of follicles through Wnt signaling pathway. This study will provide useful information for further exploration on DNA-methylation-mediated RSPO2 pathway during follicular development.

Neuroprotective effect of NDEELNK from sea cucumber ovum against scopolamine-induced PC12 cells damage through enhancing energy metabolism and upregulation of PKA/BDNF/NGF signaling pathway

2021 ◽  
Author(s):  
Yue Zhao ◽  
Yifei Dong ◽  
Qi Ge ◽  
Pengbo Cui ◽  
Na Sun ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Sea Cucumber ◽  
Molecular Mechanisms ◽  
Neuroprotective Effect ◽  
Ngf Signaling ◽  
Neuroprotective Function

The aim of study was to evaluate the neuroprotective function of sea cucumber ovum peptides-derived NDEELNK and explore underlying molecular mechanisms. NDEELNK exerted neuroprotective effect by improving the acetylcholine (ACh)...

scholarly journals Neuron-specific activation of necroptosis signaling in multiple sclerosis cortical grey matter

2021 ◽  
Vol 141 (4) ◽  
pp. 585-604 ◽  
Author(s):  
Carmen Picon ◽  
Anusha Jayaraman ◽  
Rachel James ◽  
Catriona Beck ◽  
Patricia Gallego ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Grey Matter ◽  
Molecular Mechanisms ◽  
Fold Increase ◽  
Cell Types ◽  
Meningeal Inflammation ◽  
Cortical Grey Matter

AbstractSustained exposure to pro-inflammatory cytokines in the leptomeninges is thought to play a major role in the pathogenetic mechanisms leading to cortical pathology in multiple sclerosis (MS). Although the molecular mechanisms underlying neurodegeneration in the grey matter remain unclear, several lines of evidence suggest a prominent role for tumour necrosis factor (TNF). Using cortical grey matter tissue blocks from post-mortem brains from 28 secondary progressive MS subjects and ten non-neurological controls, we describe an increase in expression of multiple steps in the TNF/TNF receptor 1 signaling pathway leading to necroptosis, including the key proteins TNFR1, FADD, RIPK1, RIPK3 and MLKL. Activation of this pathway was indicated by the phosphorylation of RIPK3 and MLKL and the formation of protein oligomers characteristic of necrosomes. In contrast, caspase-8 dependent apoptotic signaling was decreased. Upregulation of necroptotic signaling occurred predominantly in macroneurons in cortical layers II–III, with little expression in other cell types. The presence of activated necroptotic proteins in neurons was increased in MS cases with prominent meningeal inflammation, with a 30-fold increase in phosphoMLKL+ neurons in layers I–III. The density of phosphoMLKL+ neurons correlated inversely with age at death, age at progression and disease duration. In vivo induction of chronically elevated TNF and INFγ levels in the CSF in a rat model via lentiviral transduction in the meninges, triggered inflammation and neurodegeneration in the underlying cortical grey matter that was associated with increased neuronal expression of TNFR1 and activated necroptotic signaling proteins. Exposure of cultured primary rat cortical neurons to TNF induced necroptosis when apoptosis was inhibited. Our data suggest that neurons in the MS cortex are dying via TNF/TNFR1 stimulated necroptosis rather than apoptosis, possibly initiated in part by chronic meningeal inflammation. Neuronal necroptosis represents a pathogenetic mechanism that is amenable to therapeutic intervention at several points in the signaling pathway.

scholarly journals The OsOXO2, OsOXO3 and OsOXO4 Positively Regulate Panicle Blast Resistance in Rice

Rice ◽  
2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jingfang Dong ◽  
Lian Zhou ◽  
Aiqing Feng ◽  
Shaohong Zhang ◽  
Hua Fu ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Blast Resistance ◽  
Aba Signaling ◽  
Leaf Blast ◽  
Expression Levels ◽  
Panicle Blast ◽  
Localization Analysis ◽  
Sa Signaling

Abstract Background Although panicle blast is more destructive to yield loss than leaf blast in rice, the cloned genes that function in panicle blast resistance are still very limited and the molecular mechanisms underlying panicle blast resistance remain largely unknown. Results In the present study, we have confirmed that the three Oxalate oxidase (OXO) genes, OsOXO2, OsOXO3 and OsOXO4 from a blast-resistant cultivar BC10 function in panicle blast resistance in rice. The expression of OsOXO2, OsOXO3 and OsOXO4 were induced by panicle blast inoculation. Subcellular localization analysis revealed that the three OXO proteins are all localized in the nucleus and cytoplasm. Simultaneous silencing of OsOXO2, OsOXO3 and OsOXO4 decreased rice resistance to panicle blast, whereas the OsOXO2, OsOXO3 and OsOXO4 overexpression rice plants individually showed enhanced panicle blast resistance. More H2O2 and higher expression levels of PR genes were observed in the overexpressing plants than in the control plants, while the silencing plants exhibited less H2O2 and lower expression levels of PR genes compared to the control plants. Moreover, phytohormone treatment and the phytohormone signaling related gene expression analysis showed that panicle blast resistance mediated by the three OXO genes was associated with the activation of JA and ABA signaling pathways but suppression of SA signaling pathway. Conclusion OsOXO2, OsOXO3 and OsOXO4 positively regulate panicle blast resistance in rice. The OXO genes could modulate the accumulation of H2O2 and expression levels of PR gene in plants. Moreover, the OXO genes mediated panicle blast resistance could be regulated by ABA, SA and JA, and may be associated with the activation of JA and ABA signaling pathways but suppression of the SA signaling pathway.

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