Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of thrombomodulin (TM), an antithrombotic factor, was investigated during neutrophilic differentiation of the HL-60 human myeloblastic cell line treated with all-trans retinoic acid (ATRA) or dimethyl sulfoxide (DMSO). Differentiation of the cells into neutrophilic cells progressed in a time- and dose-dependent fashion with ATRA or DMSO, as confirmed by the characteristic appearance of nitroblue tetrazolium (NBT) reduction and phagocytic activities, without induction of nonspecific esterase activity. TM antigen and cofactor activity for thrombin-dependent protein C activation were not detected in untreated HL-60 cells and the cells cultured with DMSO, but were expressed in a time-dependent manner in the cells cultured with ATRA. The level of TM expression in the HL-60 cells was not dose-dependent on ATRA concentrations, but maximum TM expression was obtained at 10(-7) M ATRA. TM expression levels decreased in cells cultured with greater than 10(-6) M ATRA, although the extent of cell differentiation into neutrophilic cells progressed at the higher ATRA concentrations. Since the TM antigen levels in the ATRA-treated cells also paralleled the TM mRNA levels, the data suggests that TM induction in the HL-60 cells cultured with ATRA reflected the levels of TM biosynthesis and was independent of HL-60 differentiation into neutrophilic cells. It was postulated that the appearance of TM with cofactor activity in neutrophilic cells differentiated from leukemic cells may contribute to prevention of vascular thrombosis in differentiation therapy of patients with acute promyelocytic leukemia by ATRA.
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PMID:Thrombomodulin induction by all-trans retinoic acid is independent of HL-60 cells differentiation to neutrophilic cells. 787 35

Chemical chaperones, first defined in studies of mutant cystic fibrosis transmembrane conductance regulator proteins, are small molecules that act as stabilizers of proteins in their native state and have the ability in some cases to rescue protein-folding mutants within cells. HLA-DM is an MHC II-specific molecular chaperone that facilitates peptide loading onto MHC II proteins and also stabilizes empty MHC II molecules prior to their acquisition of antigenic peptides. APC that lack HLA-DM exhibit quantitative defects in protein Ag as well as superantigen presentation. Here we show that both the superantigen and protein presentation defect in MHC II-transfected, HLA-DM-deficient T2 cells can be partially overcome by treating the APC with the chemical chaperones glycerol, DMSO, or trimethylamine oxide. These chemical chaperones also enhance superantigen and conventional Ag presentation by wild-type APC. In vivo, glycerol was found to act as an adjuvant and resulted in enhanced IgG2a production to trinitrophenyl-keyhole limpet hemocyanin (TNP-KLH). In vitro, the enhancement of Ag presentation by chemical chaperones was found to take place at the level of the APC and took several hours to develop. Subcellular fractionation experiments show that HLA-DM enhances presentation of peptides by dense endosome fractions whereas chemical chaperones enhance presentation by light membrane fractions (early endosome or plasma membrane). The mechanism by which these chemical chaperones augment Ag presentation is not defined, but flow cytometric analysis suggests that the enhancement may be due to a subtle effect on the stability of several different proteins at the cell surface.
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PMID:Chemical chaperones enhance superantigen and conventional antigen presentation by HLA-DM-deficient as well as HLA-DM-sufficient antigen-presenting cells and enhance IgG2a production in vivo. 975 41

The infrared (4000-200 cm(-1)) spectrum for 4-amino-5-pyrimidinecarbonitrile (APC, C5H4N4) was acquired in the solid phase. In addition, the (1)H and (13)C NMR spectra of APC were obtained in DMSO-d6 along with its mass spectrum. Initially, six isomers were hypothesized and then investigated by means of DFT/B3LYP and MP2(full) quantum mechanical calculations using a 6-31G(d) basis set. Moreover, the (1)H and (13)C NMR chemical shifts were predicted using a GIAO approximation at the 6-311+G(d,p) basis set and the B3LYP method with (and without) solvent effects using PCM method. The correlation coefficients showed good agreement between the experimental/theoretical chemical shift values of amino tautomers (1 and 2) rather than the eliminated imino tautomers (3-6), in agreement with the current quantum mechanical calculations. Structures 3-6 are less stable than the amino tautomers (1 and 2) by about 5206-8673 cm(-1) (62.3-103.7 kJ/mol). The MP2(full)/6-31G(d) computational results favor the amino structure 1 with a pyramidal NH2 moiety and calculated real vibrational frequencies, however; structure 2 is considered a transition state owing to the calculated imaginary frequency. It is worth mentioning that, the calculated structural parameters suggest a strong conjugation between the amino nitrogen and pyrimidine ring. Aided by frequency calculations, normal coordinate analysis, force constants and potential energy distributions (PEDs), a complete vibrational assignment for the observed bands is proposed herein. Finally, NH2 internal rotation barriers for the stable non-planar isomer (1) were carried out using MP2(full)/6-31G(d) optimized structural parameters. Our results are discussed herein and compared to structural parameters for similar molecules whenever appropriate.
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PMID:Infrared and NMR spectra, tautomerism, vibrational assignment, normal coordinate analysis, and quantum mechanical calculations of 4-amino-5-pyrimidinecarbonitrile. 2366 6

Elevated mammalian target of rapamycin (mTOR) signaling contributes to the pathogenesis of diabetes, with increased morbidity and mortality, mainly because of cardiovascular complications. Because mTOR inhibition with rapamycin protects against ischemia/reperfusion injury, we hypothesized that rapamycin would prevent cardiac dysfunction associated with type 2 diabetes (T2D). We also investigated the possible mechanisms and novel protein targets involved in rapamycin-induced preservation of cardiac function in T2D mice. Adult male leptin receptor null, homozygous db/db, or wild type mice were treated daily for 28 days with vehicle (5% DMSO) or rapamycin (0.25 mg/kg, intraperitoneally). Cardiac function was monitored by echocardiography, and protein targets were identified by proteomics analysis. Rapamycin treatment significantly reduced body weight, heart weight, plasma glucose, triglyceride, and insulin levels in db/db mice. Fractional shortening was improved by rapamycin treatment in db/db mice. Oxidative stress as measured by glutathione levels and lipid peroxidation was significantly reduced in rapamycin-treated db/db hearts. Rapamycin blocked the enhanced phosphorylation of mTOR and S6, but not AKT in db/db hearts. Proteomic (by two-dimensional gel and mass spectrometry) and Western blot analyses identified significant changes in several cytoskeletal/contractile proteins (myosin light chain MLY2, myosin heavy chain 6, myosin-binding protein C), glucose metabolism proteins (pyruvate dehydrogenase E1, PYGB, Pgm2), and antioxidant proteins (peroxiredoxin 5, ferritin heavy chain 1) following rapamycin treatment in db/db heart. These results show that chronic rapamycin treatment prevents cardiac dysfunction in T2D mice, possibly through attenuation of oxidative stress and alteration of antioxidants and contractile as well as glucose metabolic protein expression.
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PMID:Mammalian target of rapamycin (mTOR) inhibition with rapamycin improves cardiac function in type 2 diabetic mice: potential role of attenuated oxidative stress and altered contractile protein expression. 2437 Nov 38

Electrospray ionization mass spectrometry is a valuable tool to probe noncovalent interactions. However, the integrity of the interactions in the gas-phase is heavily influenced by the ionization process. Investigating oligomerization and ligand binding of transthyretin (TTR) and the chaperone domain from prosurfactant protein C, we found that dimethyl sulfoxide (DMSO) can improve the stability of the noncovalent interactions during the electrospray process, both regarding ligand binding and the protein quaternary structure. Low amounts of DMSO can reduce in-source dissociation of native protein oligomers and their interactions with hydrophobic ligands, even under destabilizing conditions. We interpret the effects of DMSO as being derived from its enrichment in the electrospray droplets during evaporation. Protection of labile interactions can arise from the decrease in ion charges to reduce the contributions from Coulomb repulsions, as well as from the cooling effect of adduct dissociation. The protective effects of DMSO on labile protein interactions are an important property given its widespread use in protein analysis by electrospray ionization mass spectrometry (ESI-MS).
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PMID:Protective effects of dimethyl sulfoxide on labile protein interactions during electrospray ionization. 2475 26