Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Commonly used in flow cytometry, multiplexed optical probes can diagnose multiple types of cell surface marker, potentially leading to improved diagnosis accuracy in vivo. Herein, we demonstrate the targeting of two different tumor markers in models of disseminated ovarian cancer. Two ovarian cancer cell lines (SKOV3 and SHIN3) were employed; both overexpress D-galactose receptor (D-galR), but only SKOV3 overexpresses HER2/neu. Additionally, fusion tumors composed of SKOV3 and SHIN3/RFP were evaluated. Both galactosyl serum albumin-rhodamine green (GSA-RhodG), which binds D-galR, and trastuzumab-Alexa680, which binds HER2/neu, were administered to tumor-bearing mice for in vivo fluorescence imaging and in situ fluorescence microscopy. In vivo fluorescence imaging depicted 64 of 69 SKOV3 tumors (94.2%) based on their dual spectra corresponding to both RhodG and Alexa680, while all 71 SHIN3 tumors (100%) were detected based on their single spectrum corresponding only to RhodG. All 59 SHIN3 and 36 SKOV3 tumors were correctly diagnosed with in situ microscopy. Additionally, in the mixed tumor model, all tumors could be depicted using the RhodG spectrum, but only SKOV3 components also showed the Alexa680 spectrum. In conclusion, multitargeted multicolor optical imaging enabled specific in vivo diagnosis of tumors expressing distinct patterns of receptors, leading to improved diagnostic accuracy.
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PMID:Multi-targeted multi-color in vivo optical imaging in a model of disseminated peritoneal ovarian cancer. 1925 11

Tissue engineering approaches for peripheral nerve regeneration employ biodegradable scaffolds coupled with growth factors for improved performance in regeneration of large nerve injuries. Electrospun nanofibers provide a versatile platform for fabrication of scaffolds with extracellular matrix like architecture and increased surface area. Incorporation of growth factors in nanofibers have been previously demonstrated using oil in water emulsion techniques but are associated with burst release and loss of valuable growth factor. Here, we show a novel blend of polycaprolactone and bovine serum albumin (BSA) to form nanofibers containing nerve growth factors. The BSA helps in overcoming the most common drawbacks associated with hydrophobic polymers such as reduced loading efficiency, long degradation periods, and burst release. The controlled release of nerve growth factor (NGF) from the nanofibers was evaluated using enzyme linked immune sorbent assay (ELISA) and PC12 based bioassay over a 28 day time period. A sustained release of NGF was obtained for at least 28 days. PC12 bioassays confirmed the bioactivity of the NGF, and showed that the released NGF was sufficient to induce neurite outgrowth from PC12 cells throughout the period of release, therefore, demonstrating the successful incorporation and controlled release potential of PCL BSA scaffolds.
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PMID:Polycaprolactone and bovine serum albumin based nanofibers for controlled release of nerve growth factor. 1932 10

Here we demonstrate the use of a twin screw extrusion/spiral winding (TSESW) process to generate protein-encapsulated tissue engineering scaffolds. Bovine serum albumin (BSA) was distributed into PCL matrix using both wet and hot melt extrusion methods. The encapsulation efficiency and the time-dependent release rate, as well as the tertiary structure of BSA (via circular dichroism), were investigated as a function of processing method and conditions. Within the relatively narrow processing window of this demonstration study it was determined that the wet extrusion method gave rise to greater stability of the BSA on the basis of circular dichroism data. The rate of proliferation of human fetal osteoblast (hFOB) cells and the rate of mineral deposition were found to be greater for wet extruded scaffolds, presumably due to the important differences in surface topographies (smoother scaffold surfaces upon wet extrusion). Overall, these findings suggest that the twin screw extrusion/spiral winding (TSESW) process offers significant advantages and flexibility in generating a wide variety of non-cytotoxic tissue engineering scaffolds with controllable distributions of porosity, physical and chemical properties and protein concentrations that can be tailored for the specific requirements of each tissue engineering application.
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PMID:Multifunctional protein-encapsulated polycaprolactone scaffolds: fabrication and in vitro assessment for tissue engineering. 1948 Dec 53

In the present study, low doses (0.5, 1, and 2 microM) of cobalt protoporphyrin (CoPP), but not ferric protoporphyrin (FePP) or tin protoporphyrin (SnPP), significantly inhibited lipopolysaccharide (LPS) or lipoteichoic acid (LTA)-induced inducible nitric oxide (iNOS) and nitric oxide (NO) production with an increase in heme oxygenase 1 (HO-1) protein in RAW264.7 macrophages under serum-free conditions. IC(50) values of CoPP inhibition of NO and iNOS protein individually induced by LPS and LTA were around 0.25 and 1.7 microM, respectively. This suggests that CoPP is more sensitive at inhibiting NO production than iNOS protein in response to separate LPS and LTA stimulation. NO inhibition and HO-1 induction by CoPP were blocked by the separate addition of fetal bovine serum (FBS) and bovine serum albumin (BSA). Decreasing iNOS/NO production and increasing HO-1 protein by CoPP were observed with CoPP pretreatment, CoPP co-treatment, and CoPP post-treatment with LPS and LTA stimulation. LPS- and LTA-induced NOS/NO productions were significantly suppressed by the JNK inhibitor, SP600125, but not by the ERK inhibitor, PD98059, through a reduction in JNK protein phosphorylation. Transfection of a dominant negative JNK plasmid inhibited LPS- and LTA-induced iNOS/NO production and JNK protein phosphorylation, suggesting that JNK activation is involved in LPS- and LTA-induced iNOS/NO production. Additionally, CoPP inhibition of LPS- and LTA-induced JNK, but not ERK, protein phosphorylation was identified in RAW264.7 cells. Furthermore, CoPP significantly reduced NO production in a cell-mediated, but not cell-free, iNOS enzyme activity assay accompanied by HO-1 induction. However, attenuation of HO-1 protein stimulated by CoPP via transfection of HO-1 siRNA did not affect NO's inhibition of CoPP against LPS stimulation. CoPP effectively suppressing LPS- and LTA-induced iNOS/NO production through blocking JNK activation and iNOS enzyme activity via a HO-1 independent manner is first demonstrated herein.
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PMID:Cobalt protoporphyrin inhibition of lipopolysaccharide or lipoteichoic acid-induced nitric oxide production via blocking c-Jun N-terminal kinase activation and nitric oxide enzyme activity. 1949 18

On the basis of the synthesis of novel biodegradable amphiphilic MPEG-b-PCL-grafted chitooligosaccharide (COS-g-PCL-b-MPEG) copolymers, supramolecular hydrogels were fabricated rapidly via their inclusion complexation with alpha-cyclodextrin (alpha-CD) in aqueous solutions. The graft copolymers were characterized by (1)H NMR spectroscopy, gel permeation chromatography (GPC), and fluorescence measurement, and the supramolecular structure of the resultant hydrogels was confirmed by X-ray diffraction measurements. Rheological studies of as-obtained hydrogels indicate that the physical properties could be modulated by controlling the concentration and the graft content of the graft copolymers as well as the molar feed ratio of the graft to alpha-CD. The in vitro release kinetics studies of bovine serum albumin (BSA) entrapped in the hydrogels show that the drug release profiles are dependent on the supramolecular hydrogel compositions.
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PMID:Supramolecular hydrogels formed from biodegradable ternary COS-g-PCL-b-MPEG copolymer with alpha-cyclodextrin and their drug release. 1974 45

Tyrosine hydroxylase (TH) promoter activity is induced by 17beta-estradiol (E(2)) in PC12 cells expressing estradiol receptor-alpha (ERalpha) requiring a cAMP/calcium response element (CRE/CaRE) at -45. To examine whether membrane-initiated estradiol signaling is underlying this induction, cells co-transfected with TH reporter construct and ERalpha expression vector were exposed to membrane-impermeant estradiol conjugate (beta-estradiol-6-(O-carboxy-methyl) oxime-bovine serum albumin, E(2)BSA). TH promoter activity was elevated by E(2)BSA in dose- and time-dependent manner. E(2)BSA also elicited rapid phosphorylation of CRE binding protein (CREB) and increased CRE-driven promoter activity. Over-expression of dominant negative forms of CREB, with mutations in DNA binding or phosphorylation site, prevented TH promoter response to E(2)BSA. Pre-treatment with protein kinase A (PKA) and MEK inhibitors reduced E(2) dependent phosphorylation of CREB and ERK, and also decreased induction of TH promoter activity by E(2) or E(2)BSA. Blocking S-palmitoylation of ERalpha with C451A mutation and/or pre-treatment with 2-Bromopalmitate did not prevent but instead enhanced E(2) or E(2)BSA-elicited induction of TH promoter activity. These findings reveal, for the first time, that estradiol induction of TH gene transcription with ERalpha in PC12 cells involves membrane-initiated estradiol signaling, rapid activation of dual PKA/MEK signaling pathways, leading to CREB phosphorylation, acting at CRE/CaRE. The data demonstrate possible mechanism whereby estradiol affects catecholaminergic systems in vivo.
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PMID:Membrane-initiated estradiol signaling increases tyrosine hydroxylase promoter activity with ER alpha in PC12 cells. 1981 1

Mast cells are immune effector cells that are involved in allergies and inflammation through the release of mediators such as histamine, PGs, and cytokines. Uncoupling protein 2 (UCP2) is a mitochondrial protein that inhibits insulin secretion from beta cells, possibly through down-regulation of reactive oxygen species production. We hypothesized that UCP2 could also regulate mast cell activation. In this study, we show that mouse bone marrow mast cells (BMMCs) and human leukemic LAD2 mast cells express UCP2. BMMCs from Ucp2(-/-) mice exhibited greater histamine release, whereas overexpression of UCP2 in LAD2 cells reduced histamine release after both allergic and nonallergic triggers. Ucp2(-/-) BMMCs also had elevated histamine content and histidine decarboxylase expression. Histamine content was reduced by overexpression of UCP2 or treatment with the mitochondrial-targeted superoxide dismutase-mimetic (TBAP) tetrakis(4-benzoic acid) porphyrin manganese(III). Furthermore, Ucp2(-/-) BMMCs also had greater production of both IL-6 and PGD(2) as well as ERK phosphorylation, which is known to regulate PG synthesis. Intradermal administration of substance P, an activator of skin mast cells, and challenge with DNP-human serum albumin after passive sensitization induced significantly greater vascular permeability in the skin of Ucp2(-/-) mice in vivo. Our results suggest that UCP2 can regulate mast cell activation.
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PMID:Mitochondrial uncoupling protein 2 inhibits mast cell activation and reduces histamine content. 1984 69

To investigate whether vascular endothelial growth factor (VEGF) enhances cancer cell adhesion to normal microvessels, we used in vivo video microscopy to measure adhesion rates of MDA-MB-435s human breast cancer cells and ErbB2-transformed mouse mammary carcinomas in the postcapillary venules of rat mesentery. An individual postcapillary venule in the mesentery was injected via a glass micropipette with cancer cells either in a perfusate of mammalian Ringer solution containing 1% bovine serum albumin as a control, or with the addition of 1 nm VEGF for test measurements. Cell adhesion was measured as either the number of adherent cells or the fluorescence intensity of adherent cells in a vessel segment for 60 min. Our results showed that during both control and VEGF treatments, the number of adherent cells increased almost linearly with time over 60 min. The VEGF treatment increased the adhesion rates of human tumour cells and mouse carcinomas 1.9-fold and 1.8-fold, respectively, over those in control conditions. We also measured cancer cell adhesion after pretreatment of cells with an antibody blocking VEGF or an antibody blocking alpha 6 integrin, and pretreatment of the microvessel with VEGF receptor (KDR/Flk-1) inhibitor, SU1498, or anti-integrin extracellular matrix ligand antibody, anti-laminin-5. All antibodies and inhibitor significantly reduced adhesion, with anti-VEGF and SU1498 reducing it the most. Our results indicate that VEGF enhances cancer cell adhesion to the normal microvessel wall, and further suggest that VEGF and its receptor, KDR/Flk-1, as well as integrins of tumour cells and their ligands at the endothelium, contribute to mammary cancer cell adhesion to vascular endothelium in vivo.
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PMID:Vascular endothelial growth factor enhances cancer cell adhesion to microvascular endothelium in vivo. 1988 May 35

Thermo-sensitive semi-IPN hydrogels were prepared via in situ copolymerization of N-isopropylacrylamide (NIPAAm) with poly(ethylene glycol)-co-poly(epsilon-caprolactone) (PEG-co-PCL) macromer in the presence of sodium alginate by UV irradiation technology. The effects of the sodium alginate content, temperature, and salt on the swelling behavior of the as-obtained hydrogels were studied. The results showed that the swelling ratio of the hydrogels increased with the increasing sodium alginate content at the same temperature, and decreased with the increase in temperature. The salt sensitivity of the semi-IPN hydrogels was dependent on the content of sodium alginate introduced in the hydrogels. The mechanical rheology of the hydrogels and in vitro release behavior of bovine serum albumin (BSA) in situ encapsulated within the hydrogels were also investigated. It was found that the introduction of sodium alginate with semi-IPN structure improved mechanical strength of the hydrogels and the cumulative release percentage of BSA from the hydrogels. Such double-sensitive semi-IPN hydrogel materials could be exploited as potential candidates for drug delivery carriers.
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PMID:Synthesis and characterization of thermo-sensitive semi-IPN hydrogels based on poly(ethylene glycol)-co-poly(epsilon-caprolactone) macromer, N-isopropylacrylamide, and sodium alginate. 2003 Nov 20

Fucosylated glycans on pathogens are known to shape the immune response through their interaction with pattern recognition receptors, such as C-type lectin receptors (CLRs), on dendritic cells (DCs). Similar fucosylated structures are also commonly found in a variety of allergens, but their functional significance remains unclear. To test a hypothesis that allergen-associated glycans serve as the molecular patterns in functional interaction with CLRs, an enzyme-linked immunosorbent assay-based binding assay was performed to determine the binding activity of purified allergens and allergen extracts. THP-1 cells and monocyte-derived DCs (MDDCs) were investigated as a model for testing the functional effects of allergen-CLR interaction using enzyme-linked immunosorbent assay, Western blotting, and flow cytometry. Significant and saturable bindings of allergens and allergen extracts with variable binding activities to DC-specific ICAM3-grabbing non-integrin (DC-SIGN) and its related receptor, L-SIGN, were found. These include bovine serum albumin coupled with a common glycoform (fucosylated glycan lacking the alpha1,3-linked mannose) of allergens and a panel of purified allergens, including BG60 (Cyn dBG-60; Bermuda grass pollen) and Der p2 (house dust mite). The binding activity was calcium-dependent and inhibitable by fucose and Lewis-x trisaccharides (Le(x)). In THP-1 cells and human MDDCs, BG60-DC-SIGN interaction led to the activation of Raf-1 and ERK kinases and the induction of tumor necrosis factor-alpha expression. This effect could be blocked, in part, by Raf-1 inhibitor or anti-DC-SIGN antibodies and was significantly reduced in cells with DC-SIGN knockdown. These results suggest that allergens are able to interact with DC-SIGN and induce tumor necrosis factor-alpha expression in MDDCs via, in part, Raf-1 signaling pathways.
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PMID:Functional interaction of common allergens and a C-type lectin receptor, dendritic cell-specific ICAM3-grabbing non-integrin (DC-SIGN), on human dendritic cells. 2008 Sep 62


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