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)

In this work, three-dimensional porous composite scaffolds, based on poly(epsilon-caprolactone) (PCL), were fabricated through the combination of a filament winding technique and a phase inversion/salt leaching process. Sodium chloride crystals were used as the porogen agent, and poly(lactic acid) (PLA) fibers and calcium phosphates as reinforcement. The aim of the current work is to assess the effective synergistic role of bioactive particles (i.e. alpha-tricalcium phosphates (alpha-TCP)) and PLA fibers on the morphology and mechanical response of the final scaffold. Morphological investigations performed on fiber-reinforced composite scaffolds with different PCL/alpha-TCP volume ratios (0%, 13%, 20% and 26%) show a high porosity degree (ca. 80%), pore interconnection and a homogeneous distribution of pores within the scaffold. More specifically, a bimodal pore size distribution was observed. This comprised microporosity (pores with radii ranging from 0.1 to 10 microm, which were strictly related to solvent extraction) and macroporosity (pores with radii from 10 to 300 microm, which were ascribable to the leaching of porogen elements). Static compressive tests showed that the effect of alpha-TCP on the mechanical response was to increase the elastic modulus up to a maximum value of 2.21+/-0.24 MPa, depending on the concentration of alpha-TCP added. This effect may be explained through the interaction of calcium-deficient hydroxyapatite crystals, formed as a consequence of a hydrolysis reaction of alpha-TCP, and the fiber-reinforced polymer matrix. The correct balance between chemical composition and spatial organization of reinforcement systems allows the attainment of an ideal compromise between mechanical response and bioactive potential, facilitating the development of composite scaffolds for bone tissue engineering applications.
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PMID:The synergic effect of polylactide fiber and calcium phosphate particle reinforcement in poly epsilon-caprolactone-based composite scaffolds. 1857 87

Previous studies from this laboratory have characterized RAW117-P murine large cell B-cell lymphoma and its in vivo selected highly malignant and liver metastatic RAW117-H10 subline for their biological and biochemical properties. In this study, to understand the molecular basis of low and high metastatic behavior of these variant sublines, we have investigated the molecular phenotypes of these cells using differential display techniques and cDNA array analysis. Differential display analysis indicated a significant difference in expression of several genes between these two metastatic variant lymphoma cells. Further analyses of these cells using microarray showed an increased expression of several genes including uPAR1, CRE-BP1, Chop-10, IGF, insulin-like growth factor-IA, STAT6, Cyclin-D1, Cyclin-E, ERBB-3, Alpha NGF, Kruppel-like factor LKLF, (P)19INK4 in metastatic RAW117-H10 cells compared to parental RAW117-P cells. On the other hand, MIP1beta, CD14 antigen, Cathepsin B and MOD are expressed more in RAW117-P cells compared to RAW117-H10 cells. Differential expression of the selected genes was confirmed using semiquantitative RT-PCR techniques. The combination of plasminogen activator and its receptor and IGF-like growth factors, cell cycle regulatory molecules and transcription factors might provide an ideal environment for RAW117-H10 cells to metastasize to distant organs and colonize. Thus these results identify certain differentially expressed genes that are involved in the metastatic properties of these lymphoma cells and lay foundation for further in depth analyses to use this information to develop therapy for metastatic lymphoma.
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PMID:Differential gene expression in murine large cell B-cell lymphoma metastatic variants. 1860 72

Increased inflammation, fibrinolytic factors, and lipoprotein(a) (LP[a]) were associated with increased cardiovascular events in patients with type 2 diabetes, whereas higher levels of cardiorespiratory fitness (CRF) were associated with a lower incidence of cardiovascular mortality. Whether CRF is associated with inflammatory markers, fibrinolytic factors, and LP(a) in patients with type 2 diabetes was investigated. A total of 425 men with type 2 diabetes (mean age 55 +/- 8 years) who participated in a medical screening program were studied. CRF was measured using peak oxygen uptake with expired gas analysis during a symptom-limited exercise test. CRF inversely correlated with C-reactive protein (CRP; r = -0.27, p <0.05), white blood cell count (r = -0.13, p <0.05), fibrinogen (r = -0.28, p <0.05), LP(a) (r = -0.53, p <0.05), tissue plasminogen activator (t-PA) antigen (r = -0.65, p <0.05), and plasminogen activator inhibitor-1 activity (r = -0.17, p <0.05). Men in the highest tertile of CRF had significantly lower CRP, white blood cell count, fibrinogen, LP(a), and t-PA than men in the lowest tertile of CRF (all p <0.05). In separate multivariable linear regression models that adjusted for age, body mass index, smoking, lipid profiles, glucose, and systolic blood pressure, CRP (beta = -0.23, p <0.05), white blood cell count (beta = -0.16, p <0.05), fibrinogen (beta = -0.24, p <0.05), LP(a) (beta = -0.28, p <0.05), and t-PA (beta = -0.69, p <0.05) were each inversely associated with CRF. Each MET increment higher peak oxygen uptake was associated with a lower odds ratio of having abnormal LP(a) (odds ratio 0.43, 95% confidence interval 0.20 to 0.91) in a multivariate logistic regression model. In conclusion, CRF was inversely associated with inflammatory markers, fibrinolytic factors, and LP(a) in men with type 2 diabetes.
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PMID:Relation of cardiorespiratory fitness to inflammatory markers, fibrinolytic factors, and lipoprotein(a) in patients with type 2 diabetes mellitus. 1877 91

The relationship between the plasminogen activator system and integrin function is well documented but incompletely understood. The mechanism of uPAR-mediated signaling across the membrane and the molecular basis of uPAR-dependent activation of integrins remain important issues. The present study was undertaken to identify the molecular intermediates involved in the uPAR signaling pathway controlling alpha5beta1-integrin activation and fibronectin polymerization. Disruption of lipid rafts with MbetaCD or depletion of caveolin-1 by siRNA led to the inhibition of uPAR-dependent integrin activation and stimulation of fibronectin polymerization in human dermal fibroblasts. The data indicate a dual role for caveolin-1 in the uPAR signaling pathway, leading to integrin activation. Caveolin-1 functions initially as a membrane adaptor or scaffold to mediate uPAR-dependent activation of Src and EGFR. Subsequently, in its phosphorylated form, caveolin-1 acts as an accessory molecule to direct trafficking of activated EGFR to focal adhesions. These studies provide a novel paradigm for the regulation of crosstalk among integrins, growth-factor receptors and uPAR.
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PMID:A dual role for caveolin-1 in the regulation of fibronectin matrix assembly by uPAR. 1895 16

The aim of the present study is to elucidate the signaling pathway involved in death of human neuroblastoma SK-N-SH cells induced by Naja naja atra phospholipase A(2) (PLA(2)). Upon exposure to PLA(2), p38 MAPK activation, ERK inactivation, ROS generation, increase in intracellular Ca(2+) concentration, and upregulation of Fas and FasL were found in SK-N-SH cells. SB202190 (p38MAPK inhibitor) suppressed upregulation of Fas and FasL. N-Acetylcysteine (ROS scavenger) and BAPTA-AM (Ca(2+) chelator) abrogated p38 MAPK activation and upregulation of Fas and FasL expression, but restored phosphorylation of ERK. Activated ERK was found to attenuate p38 MAPK-mediated upregulation of Fas and FasL. Deprivation of catalytic activity could not diminish PLA(2)-induced cell death and Fas/FasL upregulation. Moreover, the cytotoxicity of arachidonic acid and lysophosphatidylcholine was not related to the expression of Fas and FasL. Taken together, our results indicate that PLA(2)-induced cell death is, in part, elicited by upregulation of Fas and FasL, which is regulated by Ca(2+)- and ROS-evoked p38 MAPK activation, and suggest that non-catalytic PLA(2) plays a role for the signaling pathway.
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PMID:Upregulation of Fas and FasL in Taiwan cobra phospholipase A2-treated human neuroblastoma SK-N-SH cells through ROS- and Ca2+-mediated p38 MAPK activation. 1900 58

Sphingosine 1-phosphate (S1P) is a bioactive lipid, stored and released from activated platelets, macrophages, and other mammalian cells. We previously reported that S1P induces esophageal smooth muscle contraction in freshly isolated intact cells. Here, we measured S1P-induced ERK1/2 activation and upstream signaling in cultured feline esophageal smooth muscle cells. Activation of ERK1/2 by S1P peaked at 5 min, was sustained up to 30 min, and was blocked by PTX. In contrast, S1P did not activate p38 MAPK or JNK. PTX inhibited S1P-induced ERK1/2 activation. We then used phospholipase inhibitors, DEDA for PLA(2), U73122 for PLC, and rhoCMB for PLD, to determine that ERK1/2 activation was downstream of PLC activation. The PKC inhibitors, GF109203X and chelerythrine, also suppressed ERK1/2 activation. Whereas the PTK inhibitor, genistein, partially inhibited ERK1/2 activation, the EGFR tyrosine kinase inhibitor, tyrphostin 51, had no effect. Taken together, S1P-induced ERK1/2 activation in cultured ESMCs requires a PTX-sensitive G protein, stimulation of the PLC pathway, and subsequent activation of the PKC and PTK pathways.
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PMID:Signaling mechanisms of sphingosine 1-phosphate-induced ERK1/2 activation in cultured feline esophageal smooth muscle cells. 1902 40

Several techniques have been proposed for producing porous structures or scaffolds for tissue engineering but, as yet, with no optimal solution. With regard to this topic, this paper focuses on the preparation of biocompatible nanometric filler-polymer composites organized in a network of fibers. Titanium dioxide (TiO2) or hydroxyapatite (HAP) nanopowders as the guest particles and poly(lactic acid) (L-PLA) or the blend poly(methylmethacrylate)/poly(epsilon-caprolactone) (PMMA/PCL) as the polymer carrier were selected as model systems for this purpose. A supercritical antisolvent technique was used to produce the composites. In the process developed, the non-soluble particulate filler was suspended in a polymer solution, and both components were sprayed simultaneously into supercritical carbon dioxide (scCO2). Using this technique, polymeric matrices were loaded with approximately 10-20 wt.% of inorganic phase distributed throughout the composite. Two different hybrid materials were prepared: a PMMA/PCL+TiO2 system where either fibers or microparticles were prepared by varying the molecular weight of the used PMMA; and fibers in the case of L-PLA+HAP system. After further post-processing in a three-dimensional network, these nanofibers can potentially be used as scaffolds for tissue engineering.
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PMID:Composite fibrous biomaterials for tissue engineering obtained using a supercritical CO2 antisolvent process. 1904 Dec 88

Ceramide and the metabolites including ceramide-1-phosphate (C1P) and sphingosine are reported to regulate the release of arachidonic acid (AA) and/or phospholipase A(2) (PLA(2)) activity in many cell types including lymphocytes. Recent studies established that C1P, a product of ceramide kinase, interacts directly with Ca(2+) binding regions in the C2 domain of alpha type cytosolic PLA(2) (cPLA(2)alpha), leading to translocation of the enzyme from the cytosol to the perinuclear region in cells. However, a precise mechanism for C1P-induced activation of cPLA(2)alpha has not been well elucidated; such as the phosphorylation signal caused by the extracellular signal-regulated kinases (ERK1/2) pathway, a downstream of the protein kinase C activation with 4beta-phorbol myristate acetate (PMA), is required or not. In the present study, we showed that the increase in intracellular ceramide levels (exogenously added cell permeable ceramides and an inhibition of ceramidase by (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol and the increase in C1P formation by transfection with the vector for human ceramide kinase significantly enhanced the Ca(2+) ionophore (A23187) -induced release of AA via cPLA(2)alpha's activation in CHO cells. Ceramides did not show additional effects on the release from the cells treated with the inhibitor of ceramidase. Ceramides and C2-C1P neither had effect on the intracellular mobilization of Ca(2+) nor the phosphorylation of cPLA(2)alpha in cells. A23187/PMA-induced release of AA was enhanced by ceramides and C2-C1P and by expression of ceramide kinase. Our findings suggest that C1P is a stimulatory factor on cPLA(2)alpha that is independent of the Ca(2+) signal and the PKC-ERK-mediated phosphorylation signal.
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PMID:Effects of ceramide, ceramidase inhibition and expression of ceramide kinase on cytosolic phospholipase A2alpha; additional role of ceramide-1-phosphate in phosphorylation and Ca2+ signaling. 1910 26

Poly(epsilon-caprolactone)/polylactide blend (PCL/PLA) is an interesting biomaterial because PCL and PLA present good complementarity in their physical properties and biodegradability. However, the thermodynamic incompatibility between two component polymers restricts further applications of their blend. In this work, we used functionalized multiwalled carbon nanotube (MWCNT) to control the morphology of immiscible PCL/PLA blend. The ternary PCL/PLA/MWCNTs composites were hence prepared by melt mixing for the morphology and the properties investigation. It is interesting to find that the functionalized MWCNTs are selectively dispersed in the matrix PCL phase and on the interface between two polymer phases, leading to simultaneous occurrence of thermodynamically and kinetically driven compatibility. Those interface-localized MWCNTs prevent coalescence of the discrete domains and enhance the phase interfacial adhesion as well. As a result, the phase morphology of the ternary composites is improved remarkably in contrast to that of the blank PCL/PLA blend. Owing to that unique selective interface-localization and improved phase morphology, the ternary composites present far lower rheological and conductive percolation thresholds than those of the binary composites, and also present extraordinary mechanical properties even at very low loading levels of the MWCNTs. Therefore, the amphiphilic MWCNTs are believed to act as the reinforcements as well as the compatibilizer in the immiscible PCL/PLA blend.
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PMID:Selective localization of multiwalled carbon nanotubes in poly(epsilon-caprolactone)/polylactide blend. 1914 Jul 30

Prdx6 (peroxiredoxin 6), a bifunctional protein with both GSH peroxidase and PLA(2) (phospholipase A(2)) [aiPLA(2) (acidic calcium-independent PLA(2))] activities, is responsible for the metabolism of lung surfactant phospholipids. We propose that the aiPLA(2) activity of the enzyme is regulated through phosphorylation. Incubation of isolated rat alveolar type II cells (AECII) with PMA, a PKC (protein kinase C) agonist, had no effect on Prdx6 expression but led to approximately 75% increase in aiPLA(2) activity that was abolished by pretreatment of cells with the MAPK (mitogen-activated protein kinase) inhibitors, SB202190 or PD98059. Prdx6 phosphorylation after incubation of AECII with PMA was demonstrated by autoradiography after immunoprecipitation with either anti-phosphothreonine o-phosphoserine antibodies. in vitro, several active isoforms of ERK (extracellular-signal-regulated kinase) and p38 phosphorylated Prdx6, resulting in an 11-fold increase in aiPLA(2) activity. The increased activity was calcium-independent and was abolished by the aiPLA(2) inhibitors, surfactant protein A and hexadecyl-3-trifluorethylglycero-sn-2-phospho-methanol (MJ33). The peroxidase activity of Prdx6 was unaffected by phosphorylation. Mass spectroscopic analysis of in vitro phosphorylated Prdx6 showed a unique phosphorylation site at Thr-177 and mutation of this residue abolished protein phosphorylation and the increase in MAPK-mediated activity. These results show that the MAPKs can mediate phosphorylation of Prdx6 at Thr-177 with a consequent marked increase in its aiPLA(2) activity.
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PMID:Mitogen-activated protein kinase-mediated phosphorylation of peroxiredoxin 6 regulates its phospholipase A(2) activity. 1914 Aug 3


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