scholarly journals Expression and Role of the Intermediate-Conductance Calcium-Activated Potassium Channel KCa3.1 in Glioblastoma

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Luigi Catacuzzeno ◽  
Bernard Fioretti ◽  
Fabio Franciolini
Keyword(s):  
Normal Brain ◽  
Glioblastoma Cells ◽  
Altered Expression ◽  
Functional Roles ◽  
Cell Functions ◽  
And Migration ◽  
And Function ◽  
Calcium Activated Potassium Channel ◽  
Proliferation And Migration

Glioblastomas are characterized by altered expression of several ion channels that have important consequences in cell functions associated with their aggressiveness, such as cell survival, proliferation, and migration. Data on the altered expression and function of the intermediate-conductance calcium-activated K (KCa3.1) channels in glioblastoma cells have only recently become available. This paper aims to (i) illustrate the main structural, biophysical, pharmacological, and modulatory properties of the KCa3.1 channel, (ii) provide a detailed account of data on the expression of this channel in glioblastoma cells, as compared to normal brain tissue, and (iii) critically discuss its major functional roles. Available data suggest that KCa3.1 channels (i) are highly expressed in glioblastoma cells but only scantly in the normal brain parenchima, (ii) play an important role in the control of glioblastoma cell migration. Altogether, these data suggest KCa3.1 channels as potential candidates for a targeted therapy against this tumor.

Abstract 517: The CYP4A-20-HETE System Regulation of Endothelial Progenitor Cell Functions that Associated with Angiogenesis

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Li Chen ◽  
Alexander Braverman ◽  
Frank Zhang ◽  
John Falck ◽  
Ali Syed Arbab ◽  
...  
Keyword(s):  
Progenitor Cell ◽  
Human Umbilical Cord Blood ◽  
Human Umbilical Cord ◽  
Vascular Effects ◽  
Endothelial Progenitor ◽  
Cell Functions ◽  
And Migration ◽  
Synthase Inhibitor ◽  
Proliferation And Migration

The CYP4A-20-HETE system regulates the neovascularization process via its potent vascular effects mainly on endothelial cells and vascular smooth muscle cells. Endothelial progenitor cells (EPC) also actively participate in physiological and pathological neovascularization. Our group first reported that the CYP4A-20-HETE system is present and functional in EPC derived from human umbilical cord blood (HUCB) and that EPC also respond to exogenous 20-HETE with increased proliferation and migration. We hypothesized that the angiogenic actions of the CYP4A-20-HETE system may involve regulation of EPC functions that associated with angiogenesis. In this study, we identified CYP4A11/22 as the main 20-HETE synthases in EPC derived from HUCB by real time PCR. We also examined the effects of exogenous 20-HETE on EPC adhesion since adhesion of EPC to extracellular matrix is an important aspect of EPC homing to the sites where angiogenesis is occurring. We found that 20-HETE (1 μM) increased EPC adhesion to fibronectin and SDF-1α coating by ∼40% and ∼35%, respectively. These increases in adhesion are completely abolished in the presence of 20-hydroxy-6, 15-eicosadienoic acid (20-HEDE), a 20-HETE antagonist. We further established the mouse ischemic hindlimb model to study the effects of pharmacological inhibition of the CYP4A/F-20-HETE system using the 20-HETE synthase inhibitor Dibromo-dodecenyl-methylsulfimide (DDMS) and 20-HEDE on compensatory angiogenesis in response to ischemia. Systemic treatment of animals with 10 mg/kg/day of either DDMS or 20-HEDE inhibited hindlimb compensatory angiogenesis by more than 50% without significant effects on the blood pressure. Specific targeting of the EPC-derived CYP4A-20-HETE system needs to be performed to further dissecting the role of systemic and EPC-derived 20-HETE on angiogenic processes. These findings implicates the CYP4A-20-HETE system as a novel regulator of EPC functions that are associated with angiogenesis and suggests that it can act as both an autocrine and paracrine regulatory factor.

scholarly journals Involvement of F-Actin in Chaperonin-Containing t-Complex 1 Beta Regulating Mouse Mesangial Cell Functions in a Glucose-Induction Cell Model

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Jin-Shuen Chen ◽  
Li-Chien Chang ◽  
Chia-Chao Wu ◽  
Lai-King Yeung ◽  
Yuh-Feng Lin
Keyword(s):  
Mesangial Cell ◽  
Cell Model ◽  
Cell Contraction ◽  
Small Interference Rna ◽  
Cell Functions ◽  
T Complex ◽  
Glucose Induction ◽  
And Migration ◽  
Proliferation And Migration

The aim of this study is to investigate the role of chaperonin-containing t-complex polypeptide 1 beta (CCT2) in the regulation of mouse mesangial cell (mMC) contraction, proliferation, and migration with filamentous/globular-(F/G-) actin ratio under high glucose induction. A low CCT2 mMC model induced by treatment of small interference RNA was established. Groups with and without low CCT2 induction examined in normal and high (H) glucose conditions revealed the following major results: (1) low CCT2 or H glucose showed the ability to attenuate F/G-actin ratio; (2) groups with low F/G-actin ratio all showed less cell contraction; (3) suppression of CCT2 may reduce the proliferation and migration which were originally induced by H glucose. In conclusion, CCT2 can be used as a specific regulator for mMC contraction, proliferation, and migration affected by glucose, which mechanism may involve the alteration of F-actin, particularly for cell contraction.

Differential role of Rho small GTPases in proliferation and migration of human cytomegalovirus (HCMV)-infected glioblastoma cells

2015 ◽  
Vol 70 ◽  
pp. S121-S122
Author(s):  
Melina Tseliou ◽  
Saud A. Alarifi ◽  
Saad H. Alkahtani ◽  
Ahmed Al-Qahtani ◽  
Christos Stournaras ◽  
...  
Keyword(s):  
Human Cytomegalovirus ◽  
Small Gtpases ◽  
Glioblastoma Cells ◽  
And Migration ◽  
Proliferation And Migration

scholarly journals lncRNA IGHCγ1 Acts as a ceRNA to Regulate Macrophage Inflammation via the miR-6891-3p/TLR4 Axis in Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Pengjun Zhang ◽  
Jianmei Sun ◽  
Caihong Liang ◽  
Bingjie Gu ◽  
Yang Xu ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Noncoding Rna ◽  
Luciferase Reporter ◽  
Mirna Sponge ◽  
And Migration ◽  
And Function ◽  
Competitive Endogenous Rna ◽  
Proliferation And Migration

Accumulating data have implicated that long noncoding RNA (lncRNA) plays an important role in osteoarthritis (OA), which may function as a competitive endogenous RNA (ceRNA) of microRNAs (miRNAs). lncRNA IGHCγ1 has been demonstrated to regulate inflammation and autoimmunity. Nonetheless, the altering effect of IGHCγ1 in OA remains unclear. This study is aimed at investigating the mechanism and function of lncRNA IGHCγ1 in OA. CCK-8, EdU, and transwell assays were used to estimate macrophage proliferation and migration. Fluorescence in situ hybridization (FISH) was performed to estimate the local expression of lncRNA IGHCγ1 in macrophages. Luciferase reporter assay was adopted to validate the ceRNA role of IGHCγ1 as miRNA sponge. lncRNA IGHCγ1 was primarily localized in macrophage cytoplasm and upregulated in OA. miR-6891-3p inhibited macrophage proliferation, migration, and inflammatory response by targeting TLR4, while lncRNA IGHCγ1 promoted TLR4 expression by functioning as a ceRNA for miR-6891-3p through the NF-κB signal in macrophages. This study strongly supports that lncRNA IGHCγ1 regulates inflammatory response via regulating the miR-6891-3p/TLR4/NF-κB axis in macrophages.

Serine/arginine-rich splicing factor 7 plays oncogenic roles through specific regulation of m6A RNA modification

2021 ◽  
Author(s):  
Yixian Cun ◽  
Sanqi An ◽  
Haiqing Zheng ◽  
Jing Lan ◽  
Wenfang Chen ◽  
...  
Keyword(s):  
Rna Binding ◽  
Splicing Factor ◽  
Rna Modification ◽  
Glioblastoma Cells ◽  
Single Nucleotide ◽  
Cell Proliferation And Migration ◽  
Specific Regulation ◽  
And Migration ◽  
Proliferation And Migration

Serine/Arginine-Rich Splicing Factor 7 (SRSF7), which is previously recognized as a splicing factor, has been revealed to play oncogenic roles in multiple cancers. However, the mechanisms underlying its oncogenic roles have not been well addressed. Here, based on N6-methyladenosine (m6A) co-methylation network analysis across diverse cell lines, we found SRSF7 positively correlated with glioblastoma cell-specific m6A methylation. We then proved SRSF7 is a novel m6A regulator that specifically facilitates the m6A methylation near its binding sites on the mRNAs involved in cell proliferation and migration through recruiting methyltransferase complex. Moreover, SRSF7 promotes the proliferation and migration of glioblastoma cells largely dependent on the m6A methyltransferase. The two single-nucleotide m6A sites on PBK are regulated by SRSF7 and partially mediate the effects of SRSF7 on glioblastoma cells through recognition by IGF2BP2. Together, our discovery revealed a novel role of SRSF7 in regulating m6A and timely confirmed the existence and functional importance of RNA binding protein (RBP) mediated specific regulation of m6A.

Role of microenvironment on proliferation and migration of an SDHB silenced murine Pheochromocytoma cell line

2017 ◽  
Author(s):  
Serena Martinelli ◽  
Vanessa D'Antongiovanni ◽  
Susan Richter ◽  
Letizia Canu ◽  
Tonino Ercolino ◽  
...  
Keyword(s):  
Cell Line ◽  
Pheochromocytoma Cell ◽  
And Migration ◽  
Proliferation And Migration

Glioblastoma invasion and NMDA receptors: A novel prospect

2019 ◽  
Vol 106 (3) ◽  
pp. 250-260 ◽  
Author(s):  
DN Nandakumar ◽  
P Ramaswamy ◽  
C Prasad ◽  
D Srinivas ◽  
K Goswami
Keyword(s):  
Glutamate Receptors ◽  
Cell Lines ◽  
Intracellular Signaling ◽  
Transcript Level ◽  
Glioblastoma Cells ◽  
Invasion And Migration ◽  
Matrigel Invasion ◽  
Nmdar Activation ◽  
And Migration

Purpose Glioblastoma cells create glutamate-rich tumor microenvironment, which initiates activation of ion channels and modulates downstream intracellular signaling. N-methyl-D-aspartate receptors (NMDARs; a type of glutamate receptors) have a high affinity for glutamate. The role of NMDAR activation on invasion of glioblastoma cells and the crosstalk with α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is yet to be explored. Main methods LN18, U251MG, and patient-derived glioblastoma cells were stimulated with NMDA to activate NMDAR glutamate receptors. The role of NMDAR activation on invasion and migration and its crosstalk with AMPAR were evaluated. Invasion and migration of glioblastoma cells were investigated by in vitro trans-well Matrigel invasion and trans-well migration assays, respectively. Expression of NMDARs and AMPARs at transcript level was evaluated by quantitative real-time polymerase chain reaction. Results We determined that NMDA stimulation leads to enhanced invasion in LN18, U251MG, and patient-derived glioblastoma cells, whereas inhibition of NMDAR using MK-801, a non-competitive antagonist of the NMDAR, significantly decreased the invasive capacity. Concordant with these findings, migration was significantly augmented by NMDAR in both cell lines. Furthermore, NMDA stimulation upregulated the expression of GluN2 and GluA1 subunits at the transcript level. Conclusions This study demonstrated the previously unexplored role of NMDAR in invasion of glioblastoma cells. Furthermore, the expression of the GluN2 subunit of NMDAR and the differential overexpression of the GluA1 subunit of AMPAR in both cell lines provide a plausible rationale of crosstalk between these calcium-permeable subunits in the glutamate-rich microenvironment of glioblastoma.

Exosomal miR-214-5p Released from Glioblastoma Cells Modulates Inflammatory Response of Microglia after Lipopolysaccharide Stimulation through Targeting CXCR5

2019 ◽  
Vol 18 (1) ◽  
pp. 78-87 ◽  
Author(s):  
Jian-kai Yang ◽  
Hong-jiang Liu ◽  
Yuanyu Wang ◽  
Chen Li ◽  
Ji-peng Yang ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Critical Role ◽  
Luciferase Reporter ◽  
Clinical Prognosis ◽  
Direct Target ◽  
And Migration ◽  
High Level ◽  
Cxcr5 Expression ◽  
Proliferation And Migration

Background and Objective: Exosomes communicate inter-cellularly and miRNAs play critical roles in this scenario. MiR-214-5p was implicated in multiple tumors with diverse functions uncovered. However, whether miR-214-5p is mechanistically involved in glioblastoma, especially via exosomal pathway, is still elusive. Here we sought to comprehensively address the critical role of exosomal miR-214-5p in glioblastoma (GBM) microenvironment.Methods:The relative expression of miR-214-5p was determined by real-time PCR. Cell viability and migration were measured by MTT and transwell chamber assays, respectively. The secretory cytokines were measured with ELISA kits. The regulatory effect of miR-214-5p on CXCR5 expression was interrogated by luciferase reporter assay. Protein level was analyzed by Western blot.Results:We demonstrated that miR-214-5p was aberrantly overexpressed in GBM and associated with poorer clinical prognosis. High level of miR-214-5p significantly contributed to cell proliferation and migration. GBM-derived exosomal miR-214-5p promoted inflammatory response in primary microglia upon lipopolysaccharide challenge. We further identified CXCR5 as the direct target of miR-214- 5p in this setting.Conclusion:Overexpression of miR-214-5p in GBM modulated the inflammatory response in microglia via exosomal transfer.

The role of GABAA receptor biogenesis, structure and function in epilepsy

2006 ◽  
Vol 34 (5) ◽  
pp. 863-867 ◽  
Author(s):  
S. Mizielinska ◽  
S. Greenwood ◽  
C.N. Connolly
Keyword(s):  
Gabaa Receptor ◽  
Structure And Function ◽  
Inhibitory Synapses ◽  
Normal Brain ◽  
Synaptic Targeting ◽  
Acid Type ◽  
Normal Brain Function ◽  
And Function ◽  
The Brain

Maintaining the correct balance in neuronal activation is of paramount importance to normal brain function. Imbalances due to changes in excitation or inhibition can lead to a variety of disorders ranging from the clinically extreme (e.g. epilepsy) to the more subtle (e.g. anxiety). In the brain, the most common inhibitory synapses are regulated by GABAA (γ-aminobutyric acid type A) receptors, a role commensurate with their importance as therapeutic targets. Remarkably, we still know relatively little about GABAA receptor biogenesis. Receptors are constructed as pentameric ion channels, with α and β subunits being the minimal requirement, and the incorporation of a γ subunit being necessary for benzodiazepine modulation and synaptic targeting. Insights have been provided by the discovery of several specific assembly signals within different GABAA receptor subunits. Moreover, a number of recent studies on GABAA receptor mutations associated with epilepsy have further enhanced our understanding of GABAA receptor biogenesis, structure and function.

Sign in / Sign up

Export Citation Format

Share Document