Transmembrane Control of the Mobility of Surface Receptors by Cytoskeletal Structures

1982 ◽  
pp. 79-95 ◽  
Author(s):  
Ichiro Yahara
Keyword(s):  
Surface Receptors

Intralysosomal Accumulation of Colloidal Gold-Low Density Lipoprotein Conjugates in Chloroquine-Treated Fibroblasts

1985 ◽  
Vol 43 ◽  
pp. 546-547 ◽  
Author(s):  
Dean A. Handley ◽  
Cynthia M. Arbeeny ◽  
Larry D. Witte
Keyword(s):  
Colloidal Gold ◽  
Cultured Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Coated Vesicle ◽  
Low Density ◽  
Cholesterol Esters ◽  
Cultured Fibroblasts ◽  
Surface Receptors ◽  
Ldl Particles

Low density lipoproteins (LDL) are the major cholesterol carrying particles in the blood. Using cultured cells, it has been shown that LDL particles interact with specific surface receptors and are internalized via a coated pit-coated vesicle pathway for lysosomal catabolism. This (Pathway has been visualized using LDL labeled to ferritin or colloidal gold. It is now recognized that certain lysomotropic agents, such as chloroquine, inhibit lysosomal enzymes that degrade protein and cholesterol esters. By interrupting cholesterol ester hydrolysis, chloroquine treatment results in lysosomal accumulation of cholesterol esters from internalized LDL. Using LDL conjugated to colloidal gold, we have examined the ultrastructural effects of chloroquine on lipoprotein uptake by normal cultured fibroblasts.

Ultra high resolution SEM at high voltage images individual fab fragments applied as molecular label to cell surface receptors

1989 ◽  
Vol 47 ◽  
pp. 70-71
Author(s):  
Klaus-Ruediger Peters
Keyword(s):  
High Resolution ◽  
High Energy ◽  
Metal Coating ◽  
Beam Diameter ◽  
Surface Receptors ◽  
Surface Mobility ◽  
Metal Atoms ◽  
Shadowing Effect ◽  
Imaging Mode ◽  
Deposition Techniques

Topographic ultra high resolution can now routinely be established on bulk samples in cold field emission scanning electron microscopy with a second generation of microscopes (FSEM) designed to provide 0.5 nm probe diameters. If such small probes are used for high magnification imaging, topographic contrast is so high that remarkably fine details can be imaged on 2DMSO/osmium-impregnated specimens at ribosome surfaces even without a metal coating. On TCH/osmium-impregnated specimens topographic resolution can be increased further if the SE-I imaging mode is applied. This requires that beam diameter and metal coating thickness be made smaller than the SE range of ~1 nm and background signal contributions be reduced. Subnanometer small probes can be obtained (only) at high accelerating voltages. Subnanometer thin continuous metal films can be produced under the following conditions: self-shadowing effect between metal atoms must be reduced through appropriate deposition techniques and surface mobility of metal atoms must be diminished through high energy sputtering and/or specimen cooling.

Extracellular matrix: the gatekeeper of tumor angiogenesis

2019 ◽  
Vol 47 (5) ◽  
pp. 1543-1555 ◽  
Author(s):  
Maurizio Mongiat ◽  
Simone Buraschi ◽  
Eva Andreuzzi ◽  
Thomas Neill ◽  
Renato V. Iozzo
Keyword(s):  
Extracellular Matrix ◽  
Tumor Angiogenesis ◽  
Signaling Cascades ◽  
Cancer Growth ◽  
Cell Behavior ◽  
Metastatic Progression ◽  
Surface Receptors ◽  
The Matrix ◽  
Multiple Signaling

Abstract The extracellular matrix is a network of secreted macromolecules that provides a harmonious meshwork for the growth and homeostatic development of organisms. It conveys multiple signaling cascades affecting specific surface receptors that impact cell behavior. During cancer growth, this bioactive meshwork is remodeled and enriched in newly formed blood vessels, which provide nutrients and oxygen to the growing tumor cells. Remodeling of the tumor microenvironment leads to the formation of bioactive fragments that may have a distinct function from their parent molecules, and the balance among these factors directly influence cell viability and metastatic progression. Indeed, the matrix acts as a gatekeeper by regulating the access of cancer cells to nutrients. Here, we will critically evaluate the role of selected matrix constituents in regulating tumor angiogenesis and provide up-to-date information concerning their primary mechanisms of action.

Nanotheranostic agents for neurodegenerative diseases

2020 ◽  
Vol 4 (6) ◽  
pp. 645-675
Author(s):  
Parasuraman Padmanabhan ◽  
Mathangi Palanivel ◽  
Ajay Kumar ◽  
Domokos Máthé ◽  
George K. Radda ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Neurodegenerative Diseases ◽  
Cell Types ◽  
Specific Cell ◽  
Ageing Population ◽  
Target Tissue ◽  
Therapeutic Approaches ◽  
Surface Receptors ◽  
Theranostic Agents ◽  
Preclinical Animal Models

Neurodegenerative diseases (NDDs), including Alzheimer's disease (AD) and Parkinson's disease (PD), affect the ageing population worldwide and while severely impairing the quality of life of millions, they also cause a massive economic burden to countries with progressively ageing populations. Parallel with the search for biomarkers for early detection and prediction, the pursuit for therapeutic approaches has become growingly intensive in recent years. Various prospective therapeutic approaches have been explored with an emphasis on early prevention and protection, including, but not limited to, gene therapy, stem cell therapy, immunotherapy and radiotherapy. Many pharmacological interventions have proved to be promising novel avenues, but successful applications are often hampered by the poor delivery of the therapeutics across the blood-brain-barrier (BBB). To overcome this challenge, nanoparticle (NP)-mediated drug delivery has been considered as a promising option, as NP-based drug delivery systems can be functionalized to target specific cell surface receptors and to achieve controlled and long-term release of therapeutics to the target tissue. The usefulness of NPs for loading and delivering of drugs has been extensively studied in the context of NDDs, and their biological efficacy has been demonstrated in numerous preclinical animal models. Efforts have also been made towards the development of NPs which can be used for targeting the BBB and various cell types in the brain. The main focus of this review is to briefly discuss the advantages of functionalized NPs as promising theranostic agents for the diagnosis and therapy of NDDs. We also summarize the results of diverse studies that specifically investigated the usage of different NPs for the treatment of NDDs, with a specific emphasis on AD and PD, and the associated pathophysiological changes. Finally, we offer perspectives on the existing challenges of using NPs as theranostic agents and possible futuristic approaches to improve them.

Partial Inhibition of Platelet Aggregation and Fibrinogen Binding by a Murine Monoclonal Antibody to GPIIIa: Requirement for Antibody Bivalency

1994 ◽  
Vol 72 (06) ◽  
pp. 964-972 ◽  
Author(s):  
Jeffery L Kutok ◽  
Barry S Coller
Keyword(s):  
Monoclonal Antibody ◽  
Platelet Aggregation ◽  
Murine Monoclonal Antibody ◽  
Platelet Glycoprotein ◽  
Igg Antibody ◽  
Surface Receptors ◽  
Partial Inhibition ◽  
Fibrinogen Binding ◽  
Igg Binding ◽  
Agonist Concentration

SummaryWe produced a murine monoclonal antibody, 7H2, and localized its epitope to one or more small regions on platelet glycoprotein (GP) Ilia. 7H2-IgG and 7H2-F(ab’)2 completely inhibit platelet aggregation and fibrinogen binding at low agonist concentrations, but only partially inhibit aggregation and fibrinogen binding at high agonist concentrations; 7H2-Fab has no effect on aggregation or fibrinogen binding at any agonist concentration. 7H2-IgG binds to the entire platelet population as judged by flow cytometry. At near saturating concentrations, ∼40,000 7H2-IgG antibody molecules bind per platelet. In contrast, ∼80,000 7H2 Fab molecules bind per platelet, suggesting that 7H2-IgG binding is bivalent. 7H2 was unable to inhibit fibrinogen binding to purified, immobilized GPIIb/IIIa. These data indicate that the bivalent binding of 7H2 to GPIIIa is required for its partial inhibition of fibrinogen binding to platelets, perhaps through dimerization of GPIIb/IIIa surface receptors (or more complex GPIIb/IIIa redistribution triggered by 7H2 binding) resulting in limited accessibility of fibrinogen to its binding site(s).

Role of Matrix Metalloproteinases in Degenerative Kidney Disorders

2018 ◽  
Vol 25 (15) ◽  
pp. 1805-1816 ◽  
Author(s):  
Shifa Narula ◽  
Chanderdeep Tandon ◽  
Simran Tandon
Keyword(s):  
Matrix Metalloproteinases ◽  
Transforming Growth Factor ◽  
Kidney Diseases ◽  
Transforming Growth Factor Β1 ◽  
Bioactive Molecules ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Ecm Remodeling ◽  
Surface Receptors ◽  
Calcium Dependent ◽  
Ecm Degradation

Matrix metalloproteinases (MMPs) are members of calcium dependent-zinc containing endopeptidases that play a pivotal role in extracellular matrix (ECM) remodeling. MMPs are also known to cleave non-matrix proteins, including cell surface receptors, TNF-α, angiotensin-II, growth factors, (especially transforming growth factor-β1, ΤGF- β1) plasminogen, endothelin and other bioactive molecules. The tissue inhibitors of metalloproteinases (TIMPs) inhibit the activity of MMPs and decrease ECM degradation. Various patho-physiological conditions have been linked with the imbalance of ECM synthesis and degradation. Numerous studies have reported the significance of MMPs and TIMPs in the progression of kidney pathologies, including glomerulonephritis, diabetic nephropathy, renal cancer, and nephrolithiasis. Although dysregulated activity of MMPs could directly or indirectly lead to pathological morbidities, their contribution in disease progression is still understated. Specifically, MMP activity in the kidneys and it's relation to kidney diseases has been the subject of a limited number of investigations. Therefore, the aim of the present review is to provide an updated insight of the involvement of MMPs and TIMPs in the pathogenesis of inflammatory and degenerative kidney disorders.

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