scholarly journals MAPK-directed activation of the whitefly transcription factor CREB leads to P450-mediated imidacloprid resistance

2020 ◽  
Vol 117 (19) ◽  
pp. 10246-10253 ◽  
Author(s):  
Xin Yang ◽  
Shun Deng ◽  
Xuegao Wei ◽  
Jing Yang ◽  
Qiannan Zhao ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Signaling Pathway ◽  
Gene Families ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Bzip Transcription Factor ◽  
Camp Response Element ◽  
Response Element

The evolution of insect resistance to pesticides poses a continuing threat to agriculture and human health. While much is known about the proximate molecular and biochemical mechanisms that confer resistance, far less is known about the regulation of the specific genes/gene families involved, particularly by trans-acting factors such as signal-regulated transcription factors. Here we resolve in fine detail the trans-regulation of CYP6CM1, a cytochrome P450 that confers resistance to neonicotinoid insecticides in the whitefly Bemisia tabaci, by the mitogen-activated protein kinase (MAPK)-directed activation of the transcription factor cAMP-response element binding protein (CREB). Reporter gene assays were used to identify the putative promoter of CYP6CM1, but no consistent polymorphisms were observed in the promoter of a resistant strain of B. tabaci (imidacloprid-resistant, IMR), which overexpresses this gene, compared to a susceptible strain (imidacloprid-susceptible, IMS). Investigation of potential trans-acting factors using in vitro and in vivo assays demonstrated that the bZIP transcription factor CREB directly regulates CYP6CM1 expression by binding to a cAMP-response element (CRE)-like site in the promoter of this gene. CREB is overexpressed in the IMR strain, and inhibitor, luciferase, and RNA interference assays revealed that a signaling pathway of MAPKs mediates the activation of CREB, and thus the increased expression of CYP6CM1, by phosphorylation-mediated signal transduction. Collectively, these results provide mechanistic insights into the regulation of xenobiotic responses in insects and implicate both the MAPK-signaling pathway and a transcription factor in the development of pesticide resistance.

scholarly journals Thymoquinone, a Dietary Bioactive Compound, Exerts Anti-Inflammatory Effects in Colitis by Stimulating Expression of the Colonic Epithelial PPAR-γ Transcription Factor

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1343
Author(s):  
Balaji Venkataraman ◽  
Saeeda Almarzooqi ◽  
Vishnu Raj ◽  
Abdullah T. Alhassani ◽  
Ahmad S. Alhassani ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Activity Index ◽  
Nigella Sativa ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Ppar Γ ◽  
Anti Inflammatory ◽  
Ht 29

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders with increasing incidence and prevalence worldwide. Here, we investigated thymoquinone (TQ), a naturally occurring phytochemical present in Nigella sativa, for anti-inflammatory effects in colonic inflammation. To address this, we used in vivo (mice) and in vitro (HT-29 cells) models in this investigation. Our results showed that TQ treatment significantly reduced the disease activity index (DAI), myeloperoxidase (MPO) activity, and protected colon microscopic architecture. In addition, TQ also reduced the expression of proinflammatory cytokines and mediators at both the mRNA and protein levels. Further, TQ decreased phosphorylation of the activated mitogen-activated protein kinase (MAPK) signaling pathway and nuclear factor kappa B (NF-κB) proteins and enhanced colon epithelial PPAR-γ transcription factor expression. TQ significantly decreased proinflammatory chemokines (CXCL-1 and IL-8), and mediator (COX-2) mRNA expression in HT-29 cells treated with TNF-α. TQ also increased HT-29 PPAR-γ mRNA, PPAR-γ protein expression, and PPAR-γ promoter activity. These results indicate that TQ inhibits MAPK and NF-κB signaling pathways and transcriptionally regulates PPAR-γ expression to induce potent anti-inflammatory activity in vivo and in vitro models of colon inflammation.

scholarly journals The Ebola virus soluble glycoprotein contributes to viral pathogenesis by activating the MAP kinase signaling pathway

2021 ◽  
Vol 17 (9) ◽  
pp. e1009937
Author(s):  
Wakako Furuyama ◽  
Kyle Shifflett ◽  
Heinz Feldmann ◽  
Andrea Marzi
Keyword(s):  
Signaling Pathway ◽  
Ebola Virus ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Hek293 Cells ◽  
Huh7 Cells ◽  
Mitogen Activated Protein

Ebola virus (EBOV) expresses three different glycoproteins (GPs) from its GP gene. The primary product, soluble GP (sGP), is secreted in abundance during infection. EBOV sGP has been discussed as a potential pathogenicity factor, however, little is known regarding its functional role. Here, we analyzed the role of sGP in vitro and in vivo. We show that EBOV sGP has two different functions that contribute to infectivity in tissue culture. EBOV sGP increases the uptake of virus particles into late endosomes in HEK293 cells, and it activates the mitogen-activated protein kinase (MAPK) signaling pathway leading to increased viral replication in Huh7 cells. Furthermore, we analyzed the role of EBOV sGP on pathogenicity using a well-established mouse model. We found an sGP-dependent significant titer increase of EBOV in the liver of infected animals. These results provide new mechanistic insights into EBOV pathogenicity and highlight EBOV sGP as a possible therapeutic target.

scholarly journals The hallucinogenic serotonin2A receptor agonist, DOI, promotes CREB-dependent gene expression of specific plasticity-associated genes in the rodent neocortex

2021 ◽  
Author(s):  
Lynette A. Desouza ◽  
Madhurima Benekareddy ◽  
Sashaina E. Fanibunda ◽  
Farhan Mohammad ◽  
Tamar Gur ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Map Kinase ◽  
Neuronal Plasticity ◽  
Cortical Neurons ◽  
Receptor Agonist ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element

AbstractPsychedelic compounds that target the 5-HT2A receptor are reported to evoke psychoplastogenic effects, including enhanced dendritic arborization and synaptogenesis. Transcriptional regulation of neuronal plasticity-associated genes is implicated in the cytoarchitectural effects of serotonergic psychedelics, however the transcription factors that drive this regulation are poorly elucidated. Here, we addressed the contribution of the transcription factor cAMP response element binding protein (CREB) in the regulation of neuronal plasticity-associated genes by the hallucinogenic 5-HT2A receptor agonist, DOI. In vitro studies with rat cortical neurons indicated that DOI enhances the phosphorylation of CREB (pCREB) through the MAP kinase and CaMKII pathways, with both cascades contributing to the DOI-evoked upregulation of Arc, Bdnf1, Cebpb and Egr2 expression, whilst the upregulation of Egr1 and cFos mRNA involved the MAP kinase and CaMKII pathway respectively. We observed a robust DOI-evoked increase in the expression of several neuronal plasticity-associated genes in the rat neocortex in vivo. Further, 5-HT2A receptor stimulation enhanced pCREB enrichment at putative cAMP response element (CRE) binding sites in the Arc, Bdnf1, Cebpb, cFos, but not Egr1 and Egr2, promoters in the rodent neocortex. The DOI-mediated transcriptional induction of Arc, cFos and Cebpb was significantly attenuated in the neocortex of CREB deficient (CREBαδ KO) mice. Collectively, these results indicate that the hallucinogenic 5-HT2A receptor agonist DOI leads to a rapid transcriptional upregulation of several neuronal plasticity-associated genes, with a subset of them exhibiting a CREB-dependent regulation. Our findings raise the intriguing possibility that similar to slow-acting classical antidepressants, rapid-action serotonergic psychedelics that target the 5-HT2A receptor may also recruit the transcription factor CREB to enhance the expression of neuronal plasticity-associated genes in the neocortex, which could in turn contribute to the rapid psychoplastogenic changes evoked by these compounds.

scholarly journals Bu Shen Zhu Yun Decoction Improves Endometrial Receptivity via VEGFR-2-Mediated Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Li Li ◽  
Huabo Jiang ◽  
Xuecong Wei ◽  
Dandan Geng ◽  
Ming He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Embryo Implantation ◽  
Mapk Signaling ◽  
Endometrial Receptivity ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
Nuclear Antigen ◽  
Vitro Fertilization

Vascular endothelial growth factor receptor-2 (VEGFR-2) regulates the mitogen-activated protein kinase (MAPK) signaling pathway and plays an important role in angiogenesis. Bu Shen Zhu Yun decoction (BSZYD) can improve endometrial receptivity and embryo implantation rates in patients undergoing in vitro fertilization. However, whether BSZYD improves endometrial receptivity via angiogenesis remains unclear. Here, we investigated the effects of BSZYD on the proliferation, migration, and angiogenesis of human endometrial microvascular endothelial cells (HEMECs) and found that BSZYD upregulated the expression of cyclin D1, matrix metalloproteinase 9 (MMP9), and proliferating cell nuclear antigen (PCNA) in HEMECs. Cell Counting Kit 8 assay, scratch-wound assay, and Tube Formation Assay results showed that BSZYD promoted the proliferation, migration, and angiogenesis of HEMECs. Western blot analysis results revealed the activation of the MAPK signaling pathway by BSZYD through the upregulation of VEGF and VEGFR-2 expression. Together, these findings highlight the novel mechanism underlying BSZYD-mediated improvement in endometrial receptivity through the MAPK signaling pathway.

scholarly journals Role for the Ran Binding Protein, Mog1p, in Saccharomyces cerevisiae SLN1-SKN7 Signal Transduction

2004 ◽  
Vol 3 (6) ◽  
pp. 1544-1556 ◽  
Author(s):  
Jade Mei-Yeh Lu ◽  
Robert J. Deschenes ◽  
Jan S. Fassler
Keyword(s):  
Signal Transduction ◽  
Transcription Factor ◽  
Osmotic Stress ◽  
Kinase Activity ◽  
Mitogen Activated Protein Kinase ◽  
Osmotic Response ◽  
Mitogen Activated Protein ◽  
Kinase Pathway

ABSTRACT Yeast Sln1p is an osmotic stress sensor with histidine kinase activity. Modulation of Sln1 kinase activity in response to changes in the osmotic environment regulates the activity of the osmotic response mitogen-activated protein kinase pathway and the activity of the Skn7p transcription factor, both important for adaptation to changing osmotic stress conditions. Many aspects of Sln1 function, such as how kinase activity is regulated to allow a rapid response to the continually changing osmotic environment, are not understood. To gain insight into Sln1p function, we conducted a two-hybrid screen to identify interactors. Mog1p, a protein that interacts with the yeast Ran1 homolog, Gsp1p, was identified in this screen. The interaction with Mog1p was characterized in vitro, and its importance was assessed in vivo. mog1 mutants exhibit defects in SLN1-SKN7 signal transduction and mislocalization of the Skn7p transcription factor. The requirement for Mog1p in normal localization of Skn7p to the nucleus does not fully account for the mog1-related defects in SLN1-SKN7 signal transduction, raising the possibility that Mog1p may play a role in Skn7 binding and activation of osmotic response genes.

scholarly journals YY1-modulated Long Non-coding RNA SNHG12 Predicts and Promotes Gastric Cancer Metastasis via Activating miR-218-5p/YWHAZ-dependent β-catenin: A Bed to Bench Approach

2020 ◽  
Author(s):  
Tian Qi Zhang ◽  
Qingqiang Dai ◽  
Maneesh Kumarsing Beeharry ◽  
Zhenqiang Wang ◽  
Liping Su ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Peritoneal Carcinomatosis ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Reverse Transcription ◽  
Reverse Transcription Pcr ◽  
Reporter Assays

Abstract Background: Gastric Cancer (GC) is one of the leading causes of cancer-related deaths and mortality. Long non-coding RNAs (lncRNAs) such as SNHG12 play important roles in the pathogenesis and progression of cancers. However, the role and significanve of SNHG12 in the metastasis of GC has not yet been thoroughly investigated.Methods: The SNHG12 expression pattern was detected in GC tissue samples from our faculty and cell lines using quantitative reverse transcription PCR. In vivo and in vitro gain and loss assays were conducted to observe the effects of SNHG12 regulation on GC cell metastasis potential. The underlying mechanisms of SNHG12 regulation on EMT and metastatic potential of GC cells were further determined by quantitative reverse transcription PCR, western blotting, dual luciferase reporter assays, co-immunoprecipitation, immunoprecipitation, RIP assays, TOPFlash/FOPFlash reporter assays and Ch-IP assays.Results: SNHG12 was upregulated in GC tissues and cell lines. The expression levels of SNHG12 in GC samples was significantly related to tumor invasion depth, TNM staging and lymph node metastasis, and was associated with poorer DFS and OS in the GC patients. SNHG12 was significantly highly expressed in peritoneal metastatic tissues from GC patients and mice subjects, suggesting a possible role of SNHG12 in peritoneal carcinomatosis from GC. Further in vivo and in vitro gain and loss assays indicated that SNHG12 promoted GC metastasis and EMT. Based on hypothetical bioinformatic analysis findings, our mechanistic analyses revealed that miR-218-5p was a direct target of SNHG12 and suggested that both SNHG12 and miR-218-5p could collectively regulate YWHAZ, forming the SNHG12/ miR-218-5p/YWHAZ axis, hereby decreasing the ubiquitination of β-catenin, thus activating the β-catenin signaling pathway and facilitating metastasis and EMT. Further analysis also revealed that the transcription factor YY1 could negatively modulate SNHG12 transcription.Conclusions: Our findings demonstrate that SNHG12 is be a potential prognostic marker and therapeutic target for GC. Negatively modulated by transcription factor YYI, SNHG12 promotes GC metastasis and EMT by regulating the miR-218-5p/YWHAZ axis and hence activating the β-catenin signaling pathway. Furthermore, we discovered high SNHG12 expression could be related to peritoneal carcinomatosis from GC but this requires further validation.

scholarly journals An Integration of Network Pharmacology and Experimental Verification to Investigate the Mechanism of Guizhi to Treat Nephrotic Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Dan He ◽  
Qiang Li ◽  
Guangli Du ◽  
Guofeng Meng ◽  
Jijia Sun ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Molecular Docking ◽  
Protein Expression ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Experimental Verification ◽  
Active Component ◽  
Mapk Signaling

Background: Guizhi has the pharmacological activity of anti-inflammatory. However, the effect mechanism of Guizhi against nephrotic syndrome (NS) remains unclear. A network pharmacological approach with experimental verification in vitro and in vivo was performed to investigate the potential mechanisms of Guizhi to treat NS.Methods: Active compounds and potential targets of Guizhi, as well as the related targets of NS were obtained from the public databases. The intersecting targets of Guizhi and NS were obtained through Venny 2.1.0. The key targets and signaling pathways were determined by protein-protein interaction (PPI), genes ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) analysis. And the overall network was constructed with Cytoscape. Molecular docking verification was carried out by AutoDock Vina. Finally, in vitro and in vivo experiments were performed to verify the mechanism of Guizhi to treat NS.Results: 63 intersecting targets were obtained, and the top five key targets mainly involed in NF- Kappa B and MAPK signaling pathway. In the overall network, cinnamaldehyde (CA) was the top one active compound with the highest degree value. The molecular docking showed that the top five key targets were of good binding activity with the active components of Guizhi. To in vitro experiment, CA, the main active component of Guizhi, inhibited the secretion of IL-1β, IL-6, TNF-α in LPS challenged RAW264.7 cells, and down regulated the protein expression of p-NF-κB p65 and p-p38 MAPK in LPS challenged RAW264.7 cells. In vitro experiment showed that, 24 urinary protein and renal function were increased in ADR group. To western blot, CA down regulated the protein expression of p-p38 MAPK in rats of adriamycin-induced nephropathy.Conclusion: CA might be the main active component of Guizhi to treat NS, and the underlying mechanism might mainly be achieved by inhibiting MAPK signaling pathway.

scholarly journals Transcriptional Regulation of ZNF638 in Thermogenic Cells by the cAMP Response Element Binding Protein in Male Mice

2019 ◽  
Vol 3 (12) ◽  
pp. 2326-2340 ◽  
Author(s):  
Luce Perie ◽  
Narendra Verma ◽  
Lingyan Xu ◽  
Xinran Ma ◽  
Elisabetta Mueller
Keyword(s):  
Zinc Finger ◽  
Binding Protein ◽  
Regulatory Region ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Element Binding Protein ◽  
Thermogenic Adipocytes

Abstract Zinc finger factors are implicated in a variety of cellular processes, including adipose tissue differentiation and thermogenesis. We have previously demonstrated that zinc finger protein 638 (ZNF638) is a transcriptional coactivator acting as an early regulator of adipogenesis in vitro. In this study, we show, to our knowledge for the first time, that, in vivo, ZNF638 abounds selectively in mature brown and subcutaneous fat tissues and in fully differentiated thermogenic adipocytes. Furthermore, gene expression studies revealed that ZNF638 is upregulated by cAMP modulators in vitro and by cold exposure and by pharmacological stimulation of β-adrenergic signaling in vivo. In silico analysis of the upstream regulatory region of the ZNF638 gene identified two putative cAMP response elements within 500 bp of the ZNF638 transcription start site. Detailed molecular analysis involving EMSA and chromatin immunoprecipitation assays demonstrated that cAMP response element binding protein (CREB) binds to these cAMP response element regions of the ZNF638 promoter, and functional studies revealed that CREB is necessary and sufficient to regulate the levels of ZNF638 transcripts. Taken together, these results demonstrate that ZNF638 is selectively expressed in mature thermogenic adipocytes and tissues and that its induction in response to classic stimuli that promote heat generation is mediated via CREB signaling, pointing to a possible novel role of ZNF638 in brown and beige fat tissues.

scholarly journals Anti-Breast Cancer Effect of 2-Dodecyl-6-Methoxycyclohexa-2,5-Diene-1,4-Dione in vivo and in vitro Through MAPK Signaling Pathway

2020 ◽  
Vol Volume 14 ◽  
pp. 2667-2684 ◽  
Author(s):  
Xing Zhou ◽  
Xingchun Wu ◽  
Luhui Qin ◽  
Shunyu Lu ◽  
Hongliang Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway

scholarly journals Icariin Promotes the Migration of BMSCs In Vitro and In Vivo via the MAPK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Feng Jiao ◽  
Wang Tang ◽  
He Huang ◽  
Zhaofei Zhang ◽  
Donghua Liu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mapk Signaling ◽  
Stress Fiber ◽  
Fiber Formation ◽  
Mapk Signaling Pathway ◽  
Actin Stress Fiber ◽  
Stress Fiber Formation ◽  
Actin Stress Fiber Formation

Bone marrow-derived mesenchymal stem cells (BMSCs) are widely used in tissue engineering for regenerative medicine due to their multipotent differentiation potential. However, their poor migration ability limits repair effects. Icariin (ICA), a major component of the Chinese medical herb Herba Epimedii, has been reported to accelerate the proliferation, osteogenic, and chondrogenic differentiation of BMSCs. However, it remains unknown whether ICA can enhance BMSC migration, and the possible underlying mechanisms need to be elucidated. In this study, we found that ICA significantly increased the migration capacity of BMSCs, with an optimal concentration of 1 μmol/L. Moreover, we found that ICA stimulated actin stress fiber formation in BMSCs. Our work revealed that activation of the MAPK signaling pathway was required for ICA-induced migration and actin stress fiber formation. In vivo, ICA promoted the recruitment of BMSCs to the cartilage defect region. Taken together, these results show that ICA promotes BMSC migration in vivo and in vitro by inducing actin stress fiber formation via the MAPK signaling pathway. Thus, combined administration of ICA with BMSCs has great potential in cartilage defect therapy.

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