scholarly journals Ecdysteroids

Encyclopedia ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 1267-1302
Author(s):  
René Lafont ◽  
Christine Balducci ◽  
Laurence Dinan
Keyword(s):  
Secondary Compounds ◽  
Affinity Binding ◽  
Invertebrate Predation ◽  
Ecdysteroid Receptor ◽  
Wide Range ◽  
Structural Analogues ◽  
Invertebrate Animals ◽  
Membrane Bound ◽  
Polyhydroxylated Steroids ◽  
Moulting Hormones

Ecdysteroid: member of a class of polyhydroxylated steroids found in invertebrate animals (zooecdysteroids; moulting hormones), plants (phytoecdysteroids) and fungi (mycoecdysteroids). Over 500 structural analogues are currently known. Biosynthetically, they derive from C27-, C28- or C29-sterols. The most frequently encountered analogue (in arthropods and plants) is 20-hydroxyecdysone (2β,3β,14α, 20R,22R,25-hexahydroxycholest-7-en-6-one). In arthropods, ecdysteroids occur universally and regulate development by inducing moulting and reproduction, where their action is mediated by high-affinity binding to an intracellular member of the class of nuclear receptor (NR) proteins (ecdysteroid receptor; EcR) dimerised with a second NR (USP/RxR). This receptor complex binds to specific DNA promoter sites and regulates gene expression. In plants, ecdysteroids are a class of secondary compounds, occurring in varying amounts in certain species, but not all in others. Phytoecdysteroids are believed to contribute to the reduction of invertebrate predation by acting as feeding deterrents or endocrine disruptors. Ecdysteroids also possess a wide range of positive pharmacological effects in mammals, where the mode of action involves moderate-affinity binding to plasma-membrane-bound receptors and not interaction with the classical NRs for vertebrate steroid hormones.

scholarly journals The Role of Exosomes in the Crosstalk between Adipocytes and Liver Cancer Cells

Cells ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 1988
Author(s):  
Leslimar Rios-Colon ◽  
Elena Arthur ◽  
Suryakant Niture ◽  
Qi Qi ◽  
John T. Moore ◽  
...  
Keyword(s):  
Liver Cancer ◽  
Cancer Cells ◽  
Bioactive Materials ◽  
Liver Cancer Cells ◽  
Secreted Factors ◽  
Wide Range ◽  
Pathophysiological Role ◽  
Inflammatory State ◽  
Membrane Bound

Exosomes are membrane-bound extracellular vesicles (EVs) that transport bioactive materials between cells and organs. The cargo delivered by exosomes can alter a wide range of cellular responses in recipient cells and play an important pathophysiological role in human cancers. In hepatocellular carcinoma (HCC), for example, adipocyte- and tumor-secreted factors contained in exosomes contribute to the creation of a chronic inflammatory state, which contributes to disease progression. The exosome-mediated crosstalk between adipocytes and liver cancer cells is a key aspect of a dynamic tumor microenvironment. In this review, we summarize the role of increased adiposity and the role of adipocyte-derived exosomes (AdExos) and HCC-derived exosomes (HCCExos) in the modulation of HCC progression. We also discuss recent advances regarding how malignant cells interact with the surrounding adipose tissue and employ exosomes to promote a more aggressive phenotype.

scholarly journals Correlated protein conformational states and membrane dynamics during attack by pore-forming toxins

2019 ◽  
Vol 116 (26) ◽  
pp. 12839-12844 ◽  
Author(s):  
Ilanila I. Ponmalar ◽  
Ramesh Cheerla ◽  
K. Ganapathy Ayappa ◽  
Jaydeep K. Basu
Keyword(s):  
Conformational Changes ◽  
Pore Formation ◽  
Bacterial Infections ◽  
Cell Lysis ◽  
Membrane Dynamics ◽  
Correlation Spectroscopy ◽  
Listeriolysin O ◽  
Conformational States ◽  
Wide Range ◽  
Membrane Bound

Pore-forming toxins (PFTs) are a class of proteins implicated in a wide range of virulent bacterial infections and diseases. These toxins bind to target membranes and subsequently oligomerize to form functional pores that eventually lead to cell lysis. While the protein undergoes large conformational changes on the bilayer, the connection between intermediate oligomeric states and lipid reorganization during pore formation is largely unexplored. Cholesterol-dependent cytolysins (CDCs) are a subclass of PFTs widely implicated in food poisoning and other related infections. Using a prototypical CDC, listeriolysin O (LLO), we provide a microscopic connection between pore formation, lipid dynamics, and leakage kinetics by using a combination of Förster resonance energy transfer (FRET) and fluorescence correlation spectroscopy (FCS) measurements on single giant unilamellar vesicles (GUVs). Upon exposure to LLO, two distinct populations of GUVs with widely different leakage kinetics emerge. We attribute these differences to the existence of oligomeric intermediates, sampling various membrane-bound conformational states of the protein, and their intimate coupling to lipid rearrangement and dynamics. Molecular dynamics simulations capture the influence of various membrane-bound conformational states on the lipid and cholesterol dynamics, providing molecular interpretations to the FRET and FCS experiments. Our study establishes a microscopic connection between membrane binding and conformational changes and their influence on lipid reorganization during PFT-mediated cell lysis. Additionally, our study provides insights into membrane-mediated protein interactions widely implicated in cell signaling, fusion, folding, and other biomolecular processes.

scholarly journals Human placental microvilli contain high-affinity binding sites for folate

1984 ◽  
Vol 218 (1) ◽  
pp. 75-80 ◽  
Author(s):  
T Green ◽  
H C Ford
Keyword(s):  
Binding Sites ◽  
High Capacity ◽  
Maternal Plasma ◽  
Affinity Binding ◽  
Human Term Placenta ◽  
High Affinity Binding ◽  
High Affinity ◽  
Placental Transport ◽  
Wide Range ◽  
Pteroylglutamic Acid

Uptake of [3H]pteroylglutamic acid [(3H]PteGlu) was studied in microvilli isolated from the syncytiotrophoblast of the human term placenta. The effect of changes in medium osmolality on the equilibrium uptake of [3H]PteGlu was negligible, which suggested that the observed uptake represented binding to proteins on or within the microvilli rather than translocation of the vitamin from the incubation medium to a free state in the intravesicular fluid. Equilibrium uptake experiments performed over a wide range of [3H]PteGlu concentrations disclosed a class of binding sites with an association constant of 0.3 nM-1 as well as a second class of sites with high capacity and low affinity. Binding of [3H]PteGlu at the high-affinity sites was inhibited by tetrahydrofolate and N5-methyltetrahydrofolate, but not by several other structural analogues. It is likely that the high-affinity binding sites are receptors for maternal plasma folate; however, their role in placental transport or storage of the vitamin was not delineated in these studies.

Difference in secondary compounds and chlorophylls between fibrils and main stems in the lichen Usnea longissima suggests different functional roles

2007 ◽  
Vol 39 (5) ◽  
pp. 491-494 ◽  
Author(s):  
Line Nybakken ◽  
Yngvar Gauslaa
Keyword(s):  
Quantitative Data ◽  
Usnic Acid ◽  
Secondary Compounds ◽  
Forest Canopies ◽  
Functional Roles ◽  
Wide Range ◽  
Usnea Longissima ◽  
Lichen Compounds ◽  
Fungal Genus

Usnea is a species-rich and widespread lichenized fungal genus of well-lit parts of forest canopies (Motyka 1936, 1947; Clerc 1998). The bright greenish colour of these beard lichens reflects the presence of usnic acid in the cortex, which forms a thin, but dense sleeve around the trebouxioid photobiont in the outermost parts of the medulla. Usnic acid, a widely distributed dibenzofuran derivative produced by various mycobiont genera, strongly absorbs UV-B, but also the shortest PAR wavelengths (e.g. McEvoy et al. 2006, M. McEvoy, K. A. Solhaug and Y Gauslaa unpublished). Depending on species (Halonen et al. 1998), Usnea also contains a wide range of UV-B absorbing depsidones and depsides, though these are usually assumed to be confined to the medulla. Quantitative data on lichen compounds are rare in Usnea species, particularly with respect to the intrathalline variation.

scholarly journals Two dimensional ruthenium carbide: structural and electronic features

2020 ◽  
Vol 22 (27) ◽  
pp. 15488-15495
Author(s):  
T. Gorkan ◽  
S. Demirci ◽  
S. Jahangirov ◽  
G. Gökoğlu ◽  
E. Aktürk
Keyword(s):  
Electronic Properties ◽  
Two Dimensional ◽  
Wide Range ◽  
Structural Analogues

Honeycomb monolayer structure of RuC and its structural analogues with Li coverage display peculiar electronic properties which promise wide range of applications.

scholarly journals P012 α4β7 Receptor occupancy by vedolizumab at trough time-point occurs at the membranal level and is not associated with endoscopic healing in inflammatory bowel disease patients

2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S135-S136
Author(s):  
B Ungar ◽  
Z Ben-Shatach ◽  
O Haj-Natour ◽  
M Yavzori ◽  
E Fudim ◽  
...  
Keyword(s):  
T Cells ◽  
Receptor Occupancy ◽  
Effector Memory ◽  
Median Percentage ◽  
Drug Levels ◽  
Wide Range ◽  
Significant Difference ◽  
Membrane Bound ◽  
Time Point ◽  
Receptor Saturation

Abstract Background Previous studies have shown inconclusive associations between vedolizumab trough levels and therapy outcomes. A near-complete occupancy of blood and intestinal α4β7 was exerted by vedolizumab through a wide-range of drug levels, regardless of clinical outcomes. However, these observations were not conducted specifically at the time of trough drug levels, did not include α4β7 highly expressing eosinophils and did not establish whether occupancy is in fact due to fully internalised VDZ- α4β7 complex in the target T-cell. Methods Peripheral blood (PB) and intestinal lamina propria (LP) were collected from IBD patients undergoing lower endoscopies on the day of vedolizumab infusion (trough time-point). Clinical and endoscopic scores were prospectively recorded. FACS analysis was performed using fluorescent conjugated-vedolizumab to investigate α4β7 occupancy on effector-memory T cells (CD3+CD45RO+ cells) and on eosinophils (CD49d+CD294+) in PB. Using a newly-developed dissociation assay, we also assessed the degree of membrane-bound VDZ-mediated blocked- α4β7. Results Forty-five IBD patients (16, 35% Crohn’s patients, 18, 40% in endoscopic remission) underwent clinical and endoscopic assessment just before their scheduled vedolizumab infusions. The median percentage of free α4β7 receptors at trough was 1.3% (IQR 0.5–3.7%) for PB T cells and 7.2% (IQR 3.6–23.4%) for LP T cells. No statistically significant difference was detected in α4β7 receptor saturation between patients with and without mucosal healing, both for PB (free α4β7 receptors: median 0.5%, 1.46%, IQR 0.3–1.4%, 0.9–3.5% respectively, p = 0.15) and for LP (free α4β7 receptors, median: 11.5%, 7%, IQR 3.5–24.2%, 5.8–20.9%, p = 0.88). Similarly, almost complete α4β7 receptor saturation at trough was detected among PB eosinophils (1.5% free α4β7 receptors, IQR 0.9–2.6%). Upon dissociation assay, a significant number of membrane-bound α4β7 receptors became detectable both on PB and LP T cells, with medians of 31% (IQR 24–41%), 22.2% (IQR 15–31%) respectively, and also for eosinophils, with a median of 83% (IQR 67–89%). When compared with values before dissociation, the proportion of unbound receptors was considerably lower (p < 0.001 for all analyses, respectively). Conclusion Even at trough, almost complete α4β7 receptor saturation is reached, both for PB and LP T cells, as well as for PB eosinophils, regardless of endoscopic activity status. This receptor occupancy is unrelated to receptor-internalisation and reflects a complete and continuous antigen-binding at the membranal level.

Cell growth-promoting activity of tissue inhibitor of metalloproteinases-2 (TIMP-2)

1994 ◽  
Vol 107 (9) ◽  
pp. 2373-2379 ◽  
Author(s):  
T. Hayakawa ◽  
K. Yamashita ◽  
E. Ohuchi ◽  
A. Shinagawa
Keyword(s):  
Cell Proliferation ◽  
Cell Growth ◽  
Inhibitory Activity ◽  
Affinity Binding ◽  
Tissue Inhibitor Of Metalloproteinases ◽  
Tissue Inhibitor ◽  
Raji Cells ◽  
Wide Range ◽  
Burkitt Lymphoma Cell Line ◽  
Growth Promoting

Human tissue inhibitor of metalloproteinases-2 (TIMP-2) has a potent growth-promoting activity for wide range of human, bovine and mouse cells, having an optimal concentration (10 ng/ml, 0.46 nM) that is ten-times lower than that of TIMP-1 (Hayakawa et al. (1992) FEBS Lett. 298, 29). Neither TIMP-1 complexed with progelatinase B nor TIMP-2 complexed with progelatinase A, both of which have full inhibitory activity against active forms of matrix metalloproteinases (MMPs), showed any cell growth-promoting activity. On the contrary, both reductively alkylated TIMPs had no MMP inhibitory activity, but significantly stimulated cell proliferation. These facts clearly indicate that the cell-proliferation. These facts clearly indicate that the cell-proliferating activity of TIMPs is independent of MMP inhibitory activity. We also demonstrated that [3H]thymidine was significantly incorporated into Raji cells, a Burkitt lymphoma cell line, in the presence of either 4 ng/ml of TIMP-1 or 0.1 ng/ml of TIMP-2. Under steady-state conditions at 4 degrees C, high-(Kd = 0.15 nM) and low-(35 nM) affinity binding sites for TIMP-2 were identified on Raji cells with 20,000 and 1.4 × 10(5) sites/cell, respectively. Both high- and low-affinity binding of 125I-TIMP-2 to Raji cells were competitively inhibited by unlabeled TIMP-2 but not by unlabeled TIMP-1, suggesting the presence of receptors for TIMP-2 independent from those for TIMP-1. TIMP-2 seems to be another new TIMP cell-growth factor in serum, besides TIMP-1.

scholarly journals THE INFLUENCE OF OXYGEN TENSION UPON METABOLIC RATE IN INVERTEBRATES

1924 ◽  
Vol 7 (1) ◽  
pp. 171-176 ◽  
Author(s):  
W. R. Amberson ◽  
H. S. Mayerson ◽  
W. J. Scott
Keyword(s):  
Oxygen Consumption ◽  
Metabolic Rate ◽  
Oxygen Tension ◽  
Sea Water ◽  
Wide Range ◽  
Invertebrate Animals

It is shown that in several of the higher invertebrate animals, oxygen consumption is directly proportional to the oxygen tension in the sea water, over a wide range.

NADPH oxidases and cancer

2015 ◽  
Vol 128 (12) ◽  
pp. 863-875 ◽  
Author(s):  
Krishnendu Roy ◽  
Yongzhong Wu ◽  
Jennifer L. Meitzler ◽  
Agnes Juhasz ◽  
Han Liu ◽  
...  
Keyword(s):  
Tissue Injury ◽  
Interferon Γ ◽  
Nadph Oxidases ◽  
Inflammatory Stress ◽  
Over Expression ◽  
Wide Range ◽  
Membrane Bound ◽  
Inflammatory Bowel ◽  
Factor Α ◽  
Respiratory Burst Oxidase

The mechanism by which reactive oxygen species (ROS) are produced by tumour cells remained incompletely understood until the discovery over the last 15 years of the family of NADPH oxidases (NOXs 1–5 and dual oxidases DUOX1/2) which are structural homologues of gp91phox, the major membrane-bound component of the respiratory burst oxidase of leucocytes. Knowledge of the roles of the NOX isoforms in cancer is rapidly expanding. Recent evidence suggests that both NOX1 and DUOX2 species produce ROS in the gastrointestinal tract as a result of chronic inflammatory stress; cytokine induction (by interferon-γ, tumour necrosis factor α, and interleukins IL-4 and IL-13) of NOX1 and DUOX2 may contribute to the development of colorectal and pancreatic carcinomas in patients with inflammatory bowel disease and chronic pancreatitis, respectively. NOX4 expression is increased in pre-malignant fibrotic states which may lead to carcinomas of the lung and liver. NOX5 is highly expressed in malignant melanomas, prostate cancer and Barrett's oesophagus-associated adenocarcinomas, and in the last it is related to chronic gastro-oesophageal reflux and inflammation. Over-expression of functional NOX proteins in many tissues helps to explain tissue injury and DNA damage from ROS that accompany pre-malignant conditions, as well as elucidating the potential mechanisms of NOX-related damage that contribute to both the initiation and the progression of a wide range of solid and haematopoietic malignancies.

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