scholarly journals Long-Term Enhancement of NMDA Receptor Function in Inhibitory Neurons Preferentially Modulates Potassium Channels and Cell Adhesion Molecules

2022 ◽  
Vol 12 ◽  
Author(s):  
Dan Xia ◽  
Xinyang Zhang ◽  
Di Deng ◽  
Xiaoyan Ma ◽  
Samer Masri ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Primary Auditory Cortex ◽  
Inhibitory Neurons ◽  
Brain Diseases ◽  
The Impact

Effectively enhancing the activity of inhibitory neurons has great therapeutic potentials since their reduced function/activity has significant contributions to pathology in various brain diseases. We showed previously that NMDAR positive allosteric modulator GNE-8324 and M-8324 selectively increase NMDAR activity on the inhibitory neurons and elevates their activity in vitro and in vivo. Here we examined the impact of long-term administering M-8324 on the functions and transcriptional profiling of parvalbumin-containing neurons in two representative brain regions, primary auditory cortex (Au1) and prelimbic prefrontal cortex (PrL-PFC). We found small changes in key electrophysiological parameters and RNA levels of neurotransmitter receptors, Na+ and Ca2+ channels. In contrast, large differences in cell adhesion molecules and K+ channels were found between Au1 and PrL-PFC in drug-naïve mice, and differences in cell adhesion molecules became much smaller after M-8324 treatment. There was also minor impact of M-8324 on cell cycle and apoptosis, suggesting a fine safety profile.

scholarly journals Ultrastructural localization of E-cadherin cell adhesion molecule on the cytoplasmic membrane of keratinocytes in vivo and in vitro.

1994 ◽  
Vol 42 (10) ◽  
pp. 1333-1340 ◽  
Author(s):  
Y Horiguchi ◽  
F Furukawa ◽  
M Fujita ◽  
S Imamura
Keyword(s):  
Cell Adhesion ◽  
Free Surface ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Cytoplasmic Membrane ◽  
Ultrastructural Localization ◽  
In Vivo Studies ◽  
E Cadherin

We examined the ultrastructural localization of E (epithelial)-cadherin cell adhesion molecules by immunoperoxidase electron microscopy on the epithelium of mouse intestine, epidermis of human skin, and cultured human keratinocytes. The in vivo studies demonstrated that E-cadherin was present at the intermediate junction but not at the desmosome of the mouse intestinal single epithelium, and was found on the cytoplasmic membranes of keratinocytes with condensation in the intercellular space of the desmosomes, except for the basal surface of the basal cells. In vitro studies demonstrated that keratinocytes cultured in medium containing a low Ca2+ concentration (0.1 mM) lacked the tight connection through desmosomes, and that E-cadherin showed diffuse distribution and dot-like accumulation around the free surface of the cytoplasmic membrane. In culture medium containing a high concentration of Ca2+ (0.6 mM), keratinocytes formed desmosomal adhesion structures in which E-cadherin was accumulated. The free surface of the keratinocytes in this medium showed weaker distribution and a lesser amount of dot-like accumulation of E-cadherin than that in a low Ca2+ condition. These findings suggest that the distribution pattern of the E-cadherin cell adhesion molecules on the keratinocytes is different from that on the single epithelium of the intestine, and that E-cadherin on the cytoplasmic membrane of the keratinocytes shifts to the desmosomes under physiological conditions, participating in adhesion in association with other desmosomal cadherins.

scholarly journals The Role of Epithelial and Vascular-Endothelial Cadherin in the Differentiation and Maintance of Tissue Integrity

2001 ◽  
Vol 44 (3) ◽  
pp. 83-87 ◽  
Author(s):  
Petr Nachtigal ◽  
Andrea Gojová ◽  
Vladimír Semecký
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Cell Signalling ◽  
Intercellular Junctions ◽  
Inflammatory Cells ◽  
Normal Function ◽  
E Cadherin

The present review has focused on the cell adhesion molecules from the cadherin superfamily, in particular on E- and VE-cadherin. In general, cadherins are a large group of cell adhesion molecules located at intercellular junctions called adherent junctions. They play an important role in embryogenesis and morphogenesis in animals and humans due to their adhesive and cell-signalling functions. Disturbances of the expression or function of cadherins and their associated proteins called catenins are crucial for the initiation and development of many pathological states. E-cadherin is an epithelium-specific cadherin that is required for the development and maintenance of the normal function of all epithelial cells in tissues. The loss or down-regulation of E-cadherin is a key event in the process of tumour invasion and metastasis. The assessment of E-cadherin immunoreactivity may be a useful prognostic marker in some cancers, complementary to the established prognostic factors. VE-cadherin is an endothelium-specific cadherin, which plays a relevant role in vascular homeostasis. It has been demonstrated that VE-cadherin is required for normal vasculogenesis, angiogenesis, and for the maintenance of vascular integrity. Disruption of VE-cadherin-catenin complexes by some inflammatory agents such as thrombin, by inflammatory cells, or shear stress is accompanied by an increase in vascular permeabilityin vivoandin vitro.

scholarly journals Targeting cell adhesion molecules with nanoparticles using in vivo and flow-based in vitro models of atherosclerosis

2017 ◽  
Vol 242 (8) ◽  
pp. 799-812 ◽  
Author(s):  
Khosrow Khodabandehlou ◽  
Jacqueline J Masehi-Lano ◽  
Christopher Poon ◽  
Jonathan Wang ◽  
Eun Ji Chung
Keyword(s):  
Cell Adhesion ◽  
Endothelial Cell ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Target Cell ◽  
Cell Adhesion Molecules ◽  
Cell Adhesion Molecule ◽  
In Vitro Models

Atherosclerosis is a leading cause of death worldwide; in addition to lipid dysfunction, chronic arterial wall inflammation is a key component of atherosclerosis. Techniques that target cell adhesion molecules, which are overexpressed during inflammation, are effective methods to detect and treat atherosclerosis. Specifically, research groups have identified vascular cell adhesion molecule-1, intercellular adhesion molecule-1, platelet endothelial cell adhesion molecule, and selectins (E-selectin and P-selectin) as correlated to atherogenesis. In this review, we discuss recent strategies both in vivo and in vitro that target cell adhesion molecules. First, we discuss peptide-based and antibody (Ab)-based nanoparticles utilized in vivo for diagnostic, therapeutic, and theranostic applications. Second, we discuss flow-based in vitro models that serve to reduce the traditional disadvantages of in vivo studies such as variability, time to develop the disease, and ethical burden, but preserve physiological relevance. The knowledge gained from these targeting studies can be translated into clinical solutions for improved detection, prevention, and treatment of atherosclerosis. Impact statement As atherosclerosis remains the leading cause of death, there is an urgent need to develop better tools for treatment of the disease. The ability to improve current treatments relies on enhancing the accuracy of in vitro and in vivo atherosclerotic models. While in vivo models provide all the relevant testing parameters, variability between animals and among models used is a barrier to reproducible results and comparability of NP efficacy. In vitro cultures isolate cells into microenvironments that fail to take into account flow separation and shear stress, which are characteristics of atherosclerotic lesions. Flow-based in vitro models provide more physiologically relevant platforms, bridging the gap between in vivo and 2D in vitro models. This is the first review that presents recent advances regarding endothelial cell-targeting using adhesion molecules in light of in vivo and flow-based in vitro models, providing insights for future development of optimal strategies against atherosclerosis.

scholarly journals Expression of cell adhesion molecules, chemokines and chemokine receptors involved in leukocyte traffic in rats undergoing autoimmune orchitis

Reproduction ◽  
2012 ◽  
Vol 143 (5) ◽  
pp. 651-662 ◽  
Author(s):  
V A Guazzone ◽  
P Jacobo ◽  
B Denduchis ◽  
L Lustig
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Chemokine Receptors ◽  
Inflammatory Diseases ◽  
Autoimmune Attack ◽  
Inflammatory Processes ◽  
Autoimmune Orchitis

The testis is considered an immunologically privileged site where germ cell antigens are protected from autoimmune attack. Yet in response to infections, inflammatory diseases, or trauma, there is an influx of leukocytes to testicular interstitium. Interactions between endothelial cells (EC) and circulating leukocytes are implicated in the initiation and evolution of inflammatory processes. Chemokines are a family of chemoattractant cytokines characterized by their ability to both recruit and activate cells. Thus, we investigated the expression of CCL3, its receptors, and adhesion molecules CD31 and CD106 in an in vivo model of experimental autoimmune orchitis (EAO). In EAO, the highest content of CCL3 in testicular fluid coincides with onset of the disease. However, CCL3 released in vitro by testicular macrophages is higher during the immunization period. The specific chemokine receptors, CCR1 and CCR5, were expressed by testicular monocytes/macrophages and an increased number of CCR5+ cells was associated with the degree of testicular lesion. EC also play an essential role by facilitating leukocyte recruitment via their ability to express cell surface adhesion molecules that mediate interactions with leukocytes in the bloodstream. Rats with EAO showed a significant increase in the percentage of CD31+ EC that upregulate the expression of CD106. The percentage of leukocytes isolated from peripheral blood and lymph nodes expressing CD49d (CD106 ligand) also increases during orchitis. These data suggest that cell adhesion molecules, in conjunction with chemokines, contribute to the formation of a chemotactic gradient within the testis, causing the leukocyte infiltration characteristic of EAO histopathology.

Hippocampal long-term potentiation and neural cell adhesion molecules L1 and NCAM

Nature ◽  
1994 ◽  
Vol 372 (6508) ◽  
pp. 777-779 ◽  
Author(s):  
Andreas Lüthi ◽  
Jean-Paul Laurent ◽  
Alexander Figurovt ◽  
Dominique Mullert ◽  
Melitta Schachnert
Keyword(s):  
Cell Adhesion ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Long Term Potentiation ◽  
Neural Cell ◽  
Neural Cell Adhesion Molecules ◽  
Term Potentiation ◽  
Neural Cell Adhesion

scholarly journals Tyrosine Phosphorylation at a Site Highly Conserved in the L1 Family of Cell Adhesion Molecules Abolishes Ankyrin Binding and Increases Lateral Mobility of Neurofascin

1997 ◽  
Vol 137 (3) ◽  
pp. 703-714 ◽  
Author(s):  
Timothy D. Garver ◽  
Qun Ren ◽  
Shmuel Tuvia ◽  
Vann Bennett
Keyword(s):  
Cell Adhesion ◽  
Tyrosine Phosphorylation ◽  
Adhesion Molecules ◽  
Tyrosine Kinases ◽  
Cell Adhesion Molecules ◽  
Protein Tyrosine Kinase ◽  
Neuroblastoma Cells ◽  
Cytoplasmic Domain ◽  
Lateral Mobility

This paper presents evidence that a member of the L1 family of ankyrin-binding cell adhesion molecules is a substrate for protein tyrosine kinase(s) and phosphatase(s), identifies the highly conserved FIGQY tyrosine in the cytoplasmic domain as the principal site of phosphorylation, and demonstrates that phosphorylation of the FIGQY tyrosine abolishes ankyrin-binding activity. Neurofascin expressed in neuroblastoma cells is subject to tyrosine phosphorylation after activation of tyrosine kinases by NGF or bFGF or inactivation of tyrosine phosphatases with vanadate or dephostatin. Furthermore, both neurofascin and the related molecule Nr-CAM are tyrosine phosphorylated in a developmentally regulated pattern in rat brain. The FIGQY sequence is present in the cytoplasmic domains of all members of the L1 family of neural cell adhesion molecules. Phosphorylation of the FIGQY tyrosine abolishes ankyrin binding, as determined by coimmunoprecipitation of endogenous ankyrin and in vitro ankyrin-binding assays. Measurements of fluorescence recovery after photobleaching demonstrate that phosphorylation of the FIGQY tyrosine also increases lateral mobility of neurofascin expressed in neuroblastoma cells to the same extent as removal of the cytoplasmic domain. Ankyrin binding, therefore, appears to regulate the dynamic behavior of neurofascin and is the target for regulation by tyrosine phosphorylation in response to external signals. These findings suggest that tyrosine phosphorylation at the FIGQY site represents a highly conserved mechanism, used by the entire class of L1-related cell adhesion molecules, for regulation of ankyrin-dependent connections to the spectrin skeleton.

scholarly journals Cell Adhesion Molecules in Inflammation and Immunity: Relevance to Periodontal Diseases

1994 ◽  
Vol 5 (2) ◽  
pp. 91-123 ◽  
Author(s):  
John M. Crawford ◽  
Keiko Watanabe
Keyword(s):  
Cell Adhesion ◽  
Immune Responses ◽  
Adhesion Molecules ◽  
Cell Adhesion Molecules ◽  
Current Knowledge ◽  
Close Contact ◽  
Periodontal Diseases ◽  
Inflammatory Reactions ◽  
Adhesive Interactions

Inflammatory and immune responses involve close contact between different populations of cells. These adhesive interactions mediate migration of cells to sites of inflammation and the effector functions of cells within the lesions. Recently, there has been significant progress in understanding the molecular basis of these intercellular contacts. Blocking interactions between cell adhesion molecules and their ligands has successfully suppressed inflammatory reactions in a variety of animal models in vivo. The role of the host response in periodontal disease is receiving renewed attention, but little is known of the function of cell adhesion molecules in these diseases. In this review we summarize the structure, distribution, and function of cell adhesion molecules involved in inflammatory/immune responses. The current knowledge of the distribution of cell adhesion molecules is described and the potential for modulation of cell adhesion molecule function is discussed.

scholarly journals In Vitro and In Vivo Studies of Biodegradability and Biocompatibility of Poly(εCL)-b-Poly(EtOEP)-Based Films

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 3039
Author(s):  
Ilya Nifant’ev ◽  
Andrey Shlyakhtin ◽  
Pavel Komarov ◽  
Alexander Tavtorkin ◽  
Evgeniya Kananykhina ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Block Copolymers ◽  
Polymer Films ◽  
Hydrolytic Stability ◽  
Polymer Materials ◽  
In Vivo Studies ◽  
Cytotoxicity Test ◽  
The Impact

The control of surface bioadhesive properties of the subcutaneous implants is essential for the development of biosensors and controlled drug release devices. Poly(alkyl ethylene phosphate)-based (co)polymers are structurally versatile, biocompatible and biodegradable, and may be regarded as an alternative to poly(ethylene glycol) (PEG) copolymers in the creation of antiadhesive materials. The present work reports the synthesis of block copolymers of ε-caprolactone (εCL) and 2-ethoxy-1,3,2-dioxaphospholane-2-oxide (ethyl ethylene phosphate, EtOEP) with different content of EtOEP fragments, preparation of polymer films, and the results of the study of the impact of EtOEP/εCL ratio on the hydrophilicity (contact angle of wetting), hydrolytic stability, cytotoxicity, protein and cell adhesion, and cell proliferation using umbilical cord multipotent stem cells. It was found that the increase of EtOEP/εCL ratio results in increase of hydrophilicity of the polymer films with lowering of the protein and cell adhesion. MTT cytotoxicity test showed no significant deviations in toxicity of poly(εCL) and poly(εCL)-b-poly(EtOEP)-based films. The influence of the length of poly(EtOEP)chain in block-copolymers on fibrotic reactions was analyzed using subcutaneous implantation experiments (Wistar line rats), the increase of the width of the fibrous capsule correlated with higher EtOEP/εCL ratio. However, the copolymer-based film with highest content of polyphosphate had been subjected to faster degradation with a formation of developed contact surface of poly(εCL). The rate of the degradation of polyphosphate in vivo was significantly higher than the rate of the degradation of polyphosphate in vitro, which only confirms an objective value of in vivo experiments in the development of polymer materials for biomedical applications.

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