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At least 343 records · Page 19Linked to original sources
PubMed1986

Differential inhibition of human T-lymphocyte activation by maleimide probes.

Cellular thiols are known to be involved in lymphocyte activation, differentiation, and growth. In theory, alkylation of selective cellular thiols could be used to regulate specific processes in the activation sequence by inactivating particular enzymes or structural proteins, although to date specific alkylating probes have not been reported. N-Ethylmaleimide (NEM) is a lipophilic sulfhydryl-alkylating agent that is known to block the in vitro proliferative response of T lymphocytes. NEM (10 microM) was found to be fully inhibitory in PHA, Con A, and MLC assays only when added prior to or simultaneously with the mitogens or allogeneic cells; the addition of NEM only 15 sec after stimulating the cells with PHA resulted in a loss of greater than 50% of the inhibitory activity. The addition of 50 microM 2-ME 10 min after treating the cells with NEM failed to block the inhibitory effect. NEM (10-20 microM) had no adverse effect on lymphocyte viability, but completely blocked lymphocyte agglutination in response to mitogens or allogeneic cells. The lymphocytes overcame the inhibitory effects of NEM after 48 hr in both the PHA and MLC experiments. Resumption of the proliferative response was associated with the onset of agglutination in the PHA assay. In experiments using various analogs of NEM, we noted that the presence of a nonpolar N-linked side group was necessary for inhibitory activity. Pretreatment of PBMC with NEM decreased the total cellular thiols by 50% and blocked proliferation by 99%, whereas N-hydroxymaleimide decreased the total cellular thiols by 38% but had no effect on the proliferative response. The additional 12% of the cellular thiols that react with NEM, but not NHM, account for the inhibitory effect of NEM on lymphocyte proliferation. These findings suggest that selective cellular thiols are critical for T-cell activation.

Cytotoxicity, Immunologic↗
PubMed1988

Regulation of membrane permeability by vasopressin; activation of the water permeability pathway in toad urinary bladder by N-ethyl-maleimide.

1. Vasopressin induces a rapid increase in water permeability and stimulates net sodium transport in responsive epithelia through the mediation of cAMP. 2. In amphibian urinary bladder, the increase in water permeability is dependent on an intact cytoskeleton and is associated with the exocytotic insertion of tubular vesicles containing particle aggregates (the putative water channels) into the apical membrane of the granular epithelial cells. 3. In the toad bladder, mucosal addition of NEM, 0.1 mM, elicits a slow and irreversible increase in transepithelial water flow, whilst decreasing net sodium transport. 4. The hydrosmotic response to mucosal NEM is inhibited by cellular acidification, by pretreatment with cytoskeleton-disruptive drugs, and by agents that increase cytosolic calcium. 5. Mucosal NEM potentiates the hydrosmotic response to a submaximal, but not a maximal, dose of vasopressin. 6. Mucosal NEM, like vasopressin, induces both vesicle fusion and the appearance of particle aggregates at the granular cell apical surface. 7. NEM, unlike vasopressin, does not increase cellular cAMP content. 8. Mucosal NEM appears to increase transcellular water flow by activating cellular processes normally triggered by vasopressin, at a step beyond cAMP.

Animals↗
PubMed1995

Expression and complex formation of soluble N-ethyl-maleimide-sensitive factor attachment protein (SNAP) receptors in clonal rat endocrine cells.

Syntaxin, synaptosome-associated protein 25 (SNAP-25) and synaptobrevin are neuronal receptors of N-ethylmaleimide-sensitive factor (NSF) and soluble NSF attachment protein (SNAP), cytosolic proteins essential for membrane transport. The expression of these SNAP receptors was investigated by immunoblotting in clonal endocrine cells; catecholamine-secreting adrenal medullary cells (PC12), growth hormone-secreting pituitary cells (GH3), and insulin-secreting pancreatic beta-cells (RINr and RINm5F). All of these receptors as well as NSF and SNAP are expressed in these cells and, co-immunoprecipitation experiments indicate that syntaxin is associated with SNAP-25 and synaptobrevin after solubilization. These results suggest that syntaxin, SNAP-25, and synaptobrevin form a complex and are involved in the secretion of hormones from endocrine cells by exocytosis.

Amino Acid Sequence↗
PubMed2005

Determination of WR-1065 in human blood by high-performance liquid chromatography following fluorescent derivatization by a maleimide reagent ThioGlo3.

In order to improve the sensitivity and stability of human blood samples containing WR-1065 (i.e., active metabolite of the cytoprotective agent amifostine), a high-performance liquid chromatographic method was developed and validated using fluorescent derivatization with ThioGlo3. Using a sample volume of only 100 microl, the method was specific, sensitive (limit of quantitation=10 nM in deproteinized blood or 20 nM in whole blood), accurate (error < or = 3.2%) and reproducible (CV < or = 8.7%). In addition, the stability of WR-1065 in deproteinized and derivatized blood samples was assured for at least four weeks at -20 degrees C. This method should be particularly valuable in translating the kinetic-dynamic relationship of WR-1065 in preclinical models to that in cancer patients.

Amifostine↗
PubMed1989

Selective labeling of the erythrocyte hexose carrier with a maleimide derivative of glucosamine: relationship of an exofacial sulfhydryl to carrier conformation and structure.

Sulfhydryl-reactive derivatives of glucosamine were synthesized as potentially transportable affinity labels of the human erythrocyte hexose carrier. N-Maleoylglycyl derivatives of either 6- or 2-amino-2-deoxy-D-glucopyranose were the most potent inhibitors of 3-O-methylglucose uptake, with concentrations of half-maximal irreversible inhibition of about 1 mM. Surprisingly, these derivatives were very poorly transported into erythrocytes. They reacted rather with an exofacial sulfhydryl on the carrier following a reversible binding step, the latter possibly to the exofacial substrate binding site. However, their reactivity was determined primarily by access to the exofacial sulfhydryl, which, as predicted by the one-site model of transport, required a carrier conformation with the exofacial substrate binding site exposed. Once reacted, the carrier was "locked" in a conformation unable to reorient inwardly and bind cytochalasin B. In intact erythrocytes the N-maleoylglycyl derivative of 2-[3H]glucosamine labeled predominantly an Mr 45,000-66,000 protein on gel electrophoresis in a quantitative and cytochalasin B inhibitable fashion. By use of changes in carrier conformation induced by competitive transport inhibitors in a "double" differential labeling method, virtually complete selectivity of labeling of the carrier protein was achieved, the latter permitting localization of the reactive exofacial sulfhydryl to an Mr 18,000-20,000 tryptic fragment of the carrier.

3-O-Methylglucose↗