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Discrete Subset (discrete + subset)

Distribution by Scientific Domains

Life Sciences	50%
Chemistry	50%

Selected Abstracts

Gas6 and protein S

FEBS JOURNAL, Issue 23 2006
Vitamin K-dependent ligands for the Axl receptor tyrosine kinase subfamily
Gas6 and protein S are two homologous secreted proteins that depend on vitamin K for their execution of a range of biological functions. A discrete subset of these functions is mediated through their binding to and activation of the receptor tyrosine kinases Axl, Sky and Mer. Furthermore, a hallmark of the Gas6,Axl system is the unique ability of Gas6 and protein S to tether their non receptor-binding regions to the negatively charged membranes of apoptotic cells. Numerous studies have shown the Gas6,Axl system to regulate cell survival, proliferation, migration, adhesion and phagocytosis. Consequently, altered activity/expression of its components has been detected in a variety of pathologies such as cancer and vascular, autoimmune and kidney disorders. Moreover, Axl overactivation can equally occur without ligand binding, which has implications for tumorigenesis. Further knowledge of this exquisite ligand,receptor system and the circumstances of its activation should provide the basis for development of novel therapies for the above diseases. [source]

Epidermal growth factor stimulates proton efflux from chondrocytic cells

JOURNAL OF CELLULAR PHYSIOLOGY, Issue 1 2002
Kevin E.H. Lui
Proton efflux from chondrocytes alters the extracellular pH and ionic composition of cartilage, and influences the synthesis and degradation of extracellular matrix. Epidermal growth factor (EGF) promotes chondrocyte proliferation during skeletal development and accumulates in the synovial fluid in rheumatoid arthritis. The purpose of this study was to investigate the effect of EGF on proton efflux from chondrocytes. When monitored using a Cytosensor microphysiometer, EGF was found to rapidly activate proton efflux from CFK2 chondrocytic cells and rat articular chondrocytes. The actions of EGF were concentration-dependent with half-maximal effects at 0.3,0.7 ng/ml. Partial desensitization and time-dependent recovery of the response were observed following repeated exposures to EGF. EGF-induced proton efflux was dependent on extracellular glucose, and inhibitors of Na+/H+ exchange (NHE) markedly attenuated the initial increase in proton efflux. The response was diminished by inhibitors of phosphatidylinositol 3-kinase and phospholipase C, but not by inhibitors of MEK (MAPK/ERK kinase) or protein kinase A or C. Thus, EGF-induced proton efflux involves glucose metabolism and NHE, and is regulated by a discrete subset of EGF-activated signaling pathways. In vivo, proton efflux induced by EGF may lead to an acidic environment, enhancing turnover of cartilage matrix during development and in rheumatoid arthritis. © 2002 Wiley-Liss, Inc. [source]

Superoxide dismutase content and fatty acid composition in subsets of human spermatozoa from normozoospermic, asthenozoospermic, and polyzoospermic semen samples

MOLECULAR REPRODUCTION & DEVELOPMENT, Issue 4 2003
J. Calamera
Abstract Human ejaculated sperm comprised discrete subsets of spermatozoa, with different degrees of maturation. These subpopulations can be isolated through density gradient centrifugation. Sperm from the lowest density layer show the highest content of docosahexaenoic acid and sterols, and produce the highest levels of reactive oxygen species. The main objective of this study was to determine the superoxide dismutase (SOD) content and fatty acid composition of subsets of spermatozoa isolated from normozoospermic, asthenozoospermic, and polyzoospermic semen samples. Four sperm fractions (1,4) were obtained using ISolate gradient centrifugation. Morphology, motion parameters, SOD content, and fatty acid composition were assessed in the original samples and their fractions. Overall, sperm from normozoospermic samples had higher SOD content than those of asthenozoospermic or polyzoospermic samples. Once fractionated in subsets, the sperm SOD content decreased significantly (P,<,0.0001) from fraction 1 (top) to 4 (bottom) in all three groups of samples. Fatty acid content as well as the oxidation coefficient followed the same pattern, decreasing from fraction 1 to 4 (F1,F4). Normo- and polyzoospermic samples showed similar amounts of fatty acids, while asthenozoospermic samples mostly revealed increased levels. Normozoospermic samples displayed the lowest unsaturated fatty acid (UFA)/SOD ratio. Spermatozoa from astheno- and polyzoospermic samples, two common seminal pathologies, showed higher UFA and lower SOD content than normal sperm, therefore exhibiting a higher susceptibility to peroxidative damage. F4 from all groups, containing the most mature spermatozoa, displayed the lowest polyunsaturated fatty acid and SOD content of all subsets, suggesting that excessive SOD activity as well as abundant peroxidative targets may both be deleterious to sperm function. Mol. Reprod. Dev. 66: 422,430, 2003. © 2003 Wiley-Liss, Inc. [source]

A mass spectrometry-based strategy for detecting and characterizing endogenous proteinase activities in complex biological samples

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 3 2008
Sarah Robinson
Abstract Endogenous proteinases in biological fluids such as human saliva produce a rich peptide repertoire that reflects a unique combination of enzymes, substrates, and inhibitors/activators. Accordingly, this subproteome is an interesting source of biomarkers for disease processes that either directly or indirectly involve proteolysis. However, the relevant proteinases, typically very low abundance molecules, are difficult to classify and identify. We hypothesized that a sensitive technique for monitoring accumulated peptide products in an unbiased, global manner would be very useful for detecting and profiling proteolytic activities in complex biological samples. Building on the longstanding use of 18O isotope-based approaches for the classification of proteolytic and other enzymatic processes we devised a new method for evaluating endogenous proteinases. Specifically, we showed that upon ex vivo incubation endogenous proteinases in human parotid saliva introduced 18O from isotopically enriched water into the C-terminal carboxylic groups of their peptide products. Subsequent peptide sequence determination and inhibitor profiling enabled the detection of discrete subsets of proteolytic products that were generated by different enzymes. As a proof-of-principle we used one of these fingerprints to identify the relevant activity as tissue kallikrein. We termed this technique PALeO. Our results suggest that PALeO is a rapid and highly sensitive method for globally assessing proteinase activities in complex biological samples. [source]