scholarly journals Directional migration and transcriptional analysis of oligodendrocyte precursors subjected to stimulation of electrical signal

2015 ◽  
Vol 309 (8) ◽  
pp. C532-C540 ◽  
Author(s):  
Yongchao Li ◽  
Xinkun Wang ◽  
Li Yao
Keyword(s):  
Cell Migration ◽  
Electric Fields ◽  
Quantitative Polymerase Chain Reaction ◽  
Enrichment Analysis ◽  
Central Nervous System Disease ◽  
Electrical Signal ◽  
Neural Regeneration ◽  
Mitogen Activated Protein Kinase ◽  
Transcriptional Analysis ◽  
Directional Migration

Loss of oligodendrocytes as the result of central nervous system disease causes demyelination that impairs axon function. Effective directional migration of endogenous or grafted oligodendrocyte precursor cells (OPCs) to a lesion is crucial in the neural remyelination process. In this study, the migration of OPCs in electric fields (EFs) was investigated. We found that OPCs migrated anodally in applied EFs, and the directedness and displacement of anodal migration increased significantly when the EF strength increased from 50 to 200 mV/mm. However, EFs did not significantly affect the cell migration speed. The transcriptome of OPCs subjected to EF stimulation (100 and 200 mV/mm) was analyzed using RNA sequencing (RNA-Seq), and results were verified by the reverse transcription quantitative polymerase chain reaction. A Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that the mitogen-activated protein kinase pathway that signals cell migration was significantly upregulated in cells treated with an EF of 200 mV/mm compared with control cells. Gene ontology enrichment analysis showed the downregulation of differentially expressed genes in chemotaxis. This study suggests that an applied EF is an effective cue to guiding OPC migration in neural regeneration and that transcriptional analysis contributes to the understanding of the mechanism of EF-guided cell migration.

Epidermal growth factor receptor relocalization and kinase activity are necessary for directional migration of keratinocytes in DC electric fields

1999 ◽  
Vol 112 (12) ◽  
pp. 1967-1978 ◽  
Author(s):  
K.S. Fang ◽  
E. Ionides ◽  
G. Oster ◽  
R. Nuccitelli ◽  
R.R. Isseroff
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Electric Fields ◽  
Migration Rate ◽  
Kinase Activity ◽  
Directional Migration ◽  
Epidermal Growth ◽  
Egfr Kinase ◽  
Dc Electric Fields

Human keratinocytes migrate towards the negative pole in DC electric fields of physiological strength. This directional migration is promoted by epidermal growth factor (EGF). To investigate how EGF and its receptor (EGFR) regulate this directionality, we first examined the effect of protein tyrosine kinase inhibitors, including PD158780, a specific inhibitor for EGFR, on this response. At low concentrations, PD158780 inhibited keratinocyte migration directionality, but not the rate of migration; at higher concentrations, it reduced the migration rate as well. The less specific inhibitors, genistein, lavendustin A and tyrphostin B46, reduced the migration rate, but did not affect migration directionality. These data suggest that inhibition of EGFR kinase activity alone reduces directed motility, and inhibition of multiple tyrosine kinases, including EGFR, reduces the cell migration rate. EGFR redistribution also correlates with directional migration. EGFR concentrated on the cathodal face of the cell as early as 5 minutes after exposure to electric fields. PD158780 abolished EGFR localization to the cathodal face. These data suggest that EGFR kinase activity and redistribution in the plasma membrane are required for the directional migration of keratinocytes in DC electric fields. This study provides the first insights into the mechanisms of directed cell migration in electric fields.

scholarly journals Cannabis-Derived Compounds Cannabichromene and Δ9-Tetrahydrocannabinol Interact and Exhibit Cytotoxic Activity against Urothelial Cell Carcinoma Correlated with Inhibition of Cell Migration and Cytoskeleton Organization

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 465
Author(s):  
Omer Anis ◽  
Ajjampura C. Vinayaka ◽  
Nurit Shalev ◽  
Dvora Namdar ◽  
Stalin Nadarajan ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Migration ◽  
Cytotoxic Activity ◽  
Cell Lines ◽  
High Performance ◽  
Cannabis Sativa ◽  
Cannabinoid Receptor ◽  
Quantitative Polymerase Chain Reaction ◽  
Migration And Invasion ◽  
Xtt Assay

Cannabis sativa contains more than 500 constituents, yet the anticancer properties of the vast majority of cannabis compounds remains unknown. We aimed to identify cannabis compounds and their combinations presenting cytotoxicity against bladder urothelial carcinoma (UC), the most common urinary system cancer. An XTT assay was used to determine cytotoxic activity of C. sativa extracts on T24 and HBT-9 cell lines. Extract chemical content was identified by high-performance liquid chromatography (HPLC). Fluorescence-activated cell sorting (FACS) was used to determine apoptosis and cell cycle, using stained F-actin and nuclei. Scratch and transwell assays were used to determine cell migration and invasion, respectively. Gene expression was determined by quantitative Polymerase chain reaction (PCR). The most active decarboxylated extract fraction (F7) of high-cannabidiol (CBD) C. sativa was found to contain cannabichromene (CBC) and Δ9-tetrahydrocannabinol (THC). Synergistic interaction was demonstrated between CBC + THC whereas cannabinoid receptor (CB) type 1 and type 2 inverse agonists reduced cytotoxic activity. Treatments with CBC + THC or CBD led to cell cycle arrest and cell apoptosis. CBC + THC or CBD treatments inhibited cell migration and affected F-actin integrity. Identification of active plant ingredients (API) from cannabis that induce apoptosis and affect cell migration in UC cell lines forms a basis for pre-clinical trials for UC treatment.

scholarly journals Involvement of the ERK/HIF-1α/EMT Pathway in XCL1-Induced Migration of MDA-MB-231 and SK-BR-3 Breast Cancer Cells

2020 ◽  
Vol 22 (1) ◽  
pp. 89
Author(s):  
Ha Thi Thu Do ◽  
Jungsook Cho
Keyword(s):  
Breast Cancer ◽  
Cell Migration ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Chemokine Receptor ◽  
Intracellular Signaling ◽  
Breast Cancer Cells ◽  
Epithelial Mesenchymal Transition ◽  
Mitogen Activated Protein Kinase ◽  
Mesenchymal Transition

Chemokine–receptor interactions play multiple roles in cancer progression. It was reported that the overexpression of X-C motif chemokine receptor 1 (XCR1), a specific receptor for chemokine X-C motif chemokine ligand 1 (XCL1), stimulates the migration of MDA-MB-231 triple-negative breast cancer cells. However, the exact mechanisms of this process remain to be elucidated. Our study found that XCL1 treatment markedly enhanced MDA-MB-231 cell migration. Additionally, XCL1 treatment enhanced epithelial–mesenchymal transition (EMT) of MDA-MB-231 cells via E-cadherin downregulation and upregulation of N-cadherin and vimentin as well as increases in β-catenin nucleus translocation. Furthermore, XCL1 enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and phosphorylation of extracellular signal-regulated kinase (ERK) 1/2. Notably, the effects of XCL1 on cell migration and intracellular signaling were negated by knockdown of XCR1 using siRNA, confirming XCR1-mediated actions. Treating MDA-MB-231 cells with U0126, a specific mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor, blocked XCL1-induced HIF-1α accumulation and cell migration. The effect of XCL1 on cell migration was also evaluated in ER-/HER2+ SK-BR-3 cells. XCL1 also promoted cell migration, EMT induction, HIF-1α accumulation, and ERK phosphorylation in SK-BR-3 cells. While XCL1 did not exhibit any significant impact on the matrix metalloproteinase (MMP)-2 and -9 expressions in MDA-MB-231 cells, it increased the expression of these enzymes in SK-BR-3 cells. Collectively, our results demonstrate that activation of the ERK/HIF-1α/EMT pathway is involved in the XCL1-induced migration of both MDA-MB-231 and SK-BR-3 breast cancer cells. Based on our findings, the XCL1–XCR1 interaction and its associated signaling molecules may serve as specific targets for the prevention of breast cancer cell migration and metastasis.

scholarly journals α-Synuclein, a chemoattractant, directs microglial migration via H2O2-dependent Lyn phosphorylation

2015 ◽  
Vol 112 (15) ◽  
pp. E1926-E1935 ◽  
Author(s):  
Shijun Wang ◽  
Chun-Hsien Chu ◽  
Tessandra Stewart ◽  
Carmen Ginghina ◽  
Yifei Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Migration ◽  
Neuronal Damage ◽  
Directional Migration ◽  
Chronic Neuroinflammation ◽  
Tyrosine Protein Kinase ◽  
Microglial Migration ◽  
Directional Cell Migration ◽  
Cytoskeleton Rearrangement

Malformed α-Synuclein (α-syn) aggregates in neurons are released into the extracellular space, activating microglia to induce chronic neuroinflammation that further enhances neuronal damage in α-synucleinopathies, such as Parkinson’s disease. The mechanisms by which α-syn aggregates activate and recruit microglia remain unclear, however. Here we show that α-syn aggregates act as chemoattractants to direct microglia toward damaged neurons. In addition, we describe a mechanism underlying this directional migration of microglia. Specifically, chemotaxis occurs when α-syn binds to integrin CD11b, leading to H2O2 production by NADPH oxidase. H2O2 directly attracts microglia via a process in which extracellularly generated H2O2 diffuses into the cytoplasm and tyrosine protein kinase Lyn, phosphorylates the F-actin–associated protein cortactin after sensing changes in the microglial intracellular concentration of H2O2. Finally, phosphorylated cortactin mediates actin cytoskeleton rearrangement and facilitates directional cell migration. These findings have significant implications, given that α-syn–mediated microglial migration reaches beyond Parkinson’s disease.

scholarly journals Specific Activation of Mitogen-activated Protein Kinase by Transforming Growth Factor-β Receptors in Lipid Rafts Is Required for Epithelial Cell Plasticity

2009 ◽  
Vol 20 (3) ◽  
pp. 1020-1029 ◽  
Author(s):  
Wei Zuo ◽  
Ye-Guang Chen
Keyword(s):  
Cell Migration ◽  
Growth Factor ◽  
Protein Kinase ◽  
Lipid Rafts ◽  
Transforming Growth Factor ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Coated Pits ◽  
Mapk Activation ◽  
Mitogen Activated Protein

Transforming growth factor (TGF)-β regulates a spectrum of cellular events, including cell proliferation, differentiation, and migration. In addition to the canonical Smad pathway, TGF-β can also activate mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K)/Akt, and small GTPases in a cell-specific manner. Here, we report that cholesterol depletion interfered with TGF-β–induced epithelial-mesenchymal transition (EMT) and cell migration. This interference is due to impaired activation of MAPK mediated by cholesterol-rich lipid rafts. Cholesterol-depleting agents specifically inhibited TGF-β–induced activation of extracellular signal-regulated kinase (ERK) and p38, but not Smad2/3 or Akt. Activation of ERK or p38 is required for both TGF-β–induced EMT and cell migration, whereas PI3K/Akt is necessary only for TGF-β–promoted cell migration but not for EMT. Although receptor heterocomplexes could be formed in both lipid raft and nonraft membrane compartments in response to TGF-β, receptor localization in lipid rafts, but not in clathrin-coated pits, is important for TGF-β–induced MAPK activation. Requirement of lipid rafts for MAPK activation was further confirmed by specific targeting of the intracellular domain of TGF-β type I receptor to different membrane locations. Together, our findings establish a novel link between cholesterol and EMT and cell migration, that is, cholesterol-rich lipid rafts are required for TGF-β–mediated MAPK activation, an event necessary for TGF-β–directed epithelial plasticity.

Abstract P748: Transcriptome Profiling of the Neural Stem Cell Niche and the Effect of Exercise in Restoring Neurogenesis in Type II Diabetic Mice

Stroke ◽  
2021 ◽  
Vol 52 (Suppl_1) ◽  
Author(s):  
Gratianne Rabiller ◽  
Atsushi Kanoke ◽  
Jialing Liu
Keyword(s):  
Oxidative Stress ◽  
Deleterious Effect ◽  
Wheel Running ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Cell Types ◽  
Neural Regeneration ◽  
Diabetic Mice ◽  
Middle Aged ◽  
Neurogenic Niche

Introduction: Previously we found that mice with type 2 diabetes (T2DM) exhibited an accelerated age-associated decline in neurogenesis during baseline and after ischemic stroke compared to age-matched control mice. The current study sought to delineate the transcriptome landscape involved in the impaired neurogenesis and determine if exercise can prevent the deleterious effect of T2DM on neural regeneration. Hypothesis: We hypothesize that T2DM alters signaling pathways regulating neurogenesis and daily exercise mitigates the deleterious effect on neurogenesis in the T2DM mice. Methods: Transcriptome profiling was performed by single cell RNA sequencing (scRNAseq) of SVZ and DG cells in stroke and non-stroke mice using the 10X Genomics platform. T2DM-induced differential gene expression was analyzed by ClusterProfiler and Wikipathways enrichment analysis. Middle-aged (~260 days old) and old (~700 days old) db/+ or db/db mice were subjected to daily wheel-running exercise for one month. BrdU at 50 mg/kg twice daily for 2 consecutive days was injected i.p. at the end of the experiment to track proliferating neuroprogenitor cells. DCX+ cells and BrDU+ cells were quantified in the dentate gyrus of the hippocampus. Results: The scRNAseq analysis revealed multiple cell types co-existing in the neurogenic niche. GO and Wikipathways enrichment analysis showed that under diabetic condition, genes such as Qdpr, Hsp90ab1, Hsp90aa1, and Sox9 were downregulated in pathways involving eNOS activation; whereas Junb, C1qc, C1qb and C1qa were upregulated in the pathways related to oxidative stress. Exercise, known to increase eNOS expression and reduce oxidative stress-induced cell death, significantly restored the number of DCX+ immature neurons in 8-months-old diabetic mice almost to the level of the control mice without exercise Conclusions: Exercise restores neurogenesis by increasing the number of neuroblasts in the middle-aged diabetic mice. Ongoing experiment will investigate whether exercise promotes neurogenesis by enhancing eNOS and improved blood flow, and inducing genes involved in the survival of the NSC niche of the diabetic mice.

scholarly journals Fibroblast growth factors activate mitogen-activated protein kinase pathways to promote migration in ovine trophoblast cells

Reproduction ◽  
2011 ◽  
Vol 141 (5) ◽  
pp. 707-714 ◽  
Author(s):  
Qi En Yang ◽  
Mariana I Giassetti ◽  
Alan D Ealy
Keyword(s):  
Cell Migration ◽  
Growth Factors ◽  
Fibroblast Growth Factors ◽  
Mitogen Activated Protein Kinase ◽  
Fibroblast Growth ◽  
Trophoblast Cells ◽  
Migratory Activity ◽  
Mapk Cascades ◽  
Mitogen Activated Protein ◽  
Cattle And Sheep

Fibroblast growth factors (FGFs) 2 and FGF10 are uterine- and conceptus-derived factors that mediate trophoblast activities in cattle and sheep. To extend our understanding of how FGFs may control peri-implantation development in ruminants, we determined whether FGF2 and FGF10 impact trophoblast cell migration. Transwell inserts containing 8 μm pores were used to examine whether FGF2 or FGF10 supplementation increased oTr1 cell migration. Supplementation with 0.5 ng/ml FGF2 or FGF10 did not affect oTr1 cell migration number, but exposure to 5 or 50 ng/ml FGF2 or FGF10 increased (P<0.05) oTr1 cell migration when compared with controls. The involvement of specific MAP kinase (MAPK) cascades in mediating this FGF response was examined by using pharmacological inhibitors of specific MAPKs. Western blot analysis indicated that FGF2 and FGF10 increased phosphorylation status of MAPKs 1, 3, 8, 9, and 14. Exposure to specific inhibitors blocked FGF induction of each MAPK. Exposure to inhibitors before supplementation with FGF2 or FGF10 prevented FGF induction of cell migration, indicating that each of these signaling molecules was required for FGF effects. A final series of studies examined whether FGF2 and FGF10 also mediated the migration of a bovine trophoblast line (CT1 cell). Increases in migration were detected in each cell line by supplementing 5 or 50 ng/ml FGF2 or FGF10 (P<0.05). In summary, FGF2 and FGF10 regulate migratory activity of ovine trophoblast cells through MAPK-dependent pathways. These outcomes provide further evidence that FGFs function as mediators of peri-implantation conceptus development in cattle and sheep.

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