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

---

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

Mn(2+) was found to induce adhesion of HT29-D4 adenoma carcinoma cells to fibrinogen (Fb). This was independent of the expression of the beta3 integrin subunit and involved endogenous alphavbeta6 but not alphavbeta5 integrin. Thus, addition of Mn(2+) led to a change in integrin alphavbeta6 specificity. Furthermore, Mn(2+) was found to strongly activate the extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in the HT29-D4 cell line. As a MAPK inhibitor strongly reduced the Mn(2+)-induced cell adhesion to Fb, it is suggested that a link between MAPK activation and cell adhesion to Fb exists. Both expression and activity of matrix metalloproteinase-9 (MMP-9) were enhanced by Mn(2+) and this led to Fb processing. MMP inhibitors prevented Mn(2+)-mediated cell adhesion to Fb, leading us to suggest that Mn(2+) promoted convergent changes in integrin alphavbeta6 conformation and Fb structure through activation of ERK/MAPK and MMP-9. Finally, we found that Mn(2+) and activators of the ERK pathway cooperated in HT29-D4 cell adhesion to Fb. Such a process may be involved in bone metastasis of some cancer cells.
...
PMID:Integrin alphavbeta6 mediates HT29-D4 cell adhesion to MMP-processed fibrinogen in the presence of Mn2+. 1727 49

To date, only 1 report describes an anaplastic large cell lymphoma (ALCL) associated with hemophagocytosis in the pediatric population. To better characterize this unusual manifestation of ALCL, we identified 2 additional cases. Both patients had fever, cytopenia, decreased fibrinogen level, mediastinal or hilar adenopathy, minimal to no peripheral adenopathy, and lung infiltrates. Bone marrow biopsies and aspirates revealed striking hemophagocytosis but no ALCL. One patient fulfilled the criteria for hemophagocytic syndrome, but the other lacked 1 criterion. Both patients were initially given a misdiagnosis of infection-associated hemophagocytosis. Definitive diagnosis required lymph node biopsies that showed CD30+, anaplastic lymphoma kinase-l+ ALCL. Both tumors responded to standard lymphoma chemotherapy. One patient achieved complete remission, whereas the other patient died of complications after 2 cycles of therapy. These findings are similar to the first reported case and indicate that pediatric ALCL can manifest with an unusual constellation of symptoms consisting of hemophagocytosis, mediastinal or hilar adenopathy, and lung infiltrates.
...
PMID:Mediastinal adenopathy, lung infiltrates, and hemophagocytosis: unusual manifestation of pediatric anaplastic large cell lymphoma: report of two cases. 1727 37

Endothelial progenitor cells (EPCs) have been implicated in vascular repair and found to be functionally impaired in patients with diabetes. We evaluated the effects of the anti-diabetic drug pioglitazone on human EPC function and the involvement of PPAR-gamma and TGF-beta1. EPCs in culture were characterized at day 7 by the development of colony-forming units (CFUs) and flow cytometry assessment of differentiation marker (DiI-ac-LDL/lectin, KDR and CD31). Adhesion on fibronectin and fibrinogen in flow was analyzed as functional parameter. Treatment with pioglitazone for 72 hours increased the number of EPC-CFUs, DiI-ac-LDL(+)/lectin(+), CD31(+) and KDR(+) EPCs at 1 microM but not at 10 microM. Since pioglitazone did not significantly alter proliferation and apoptosis in cultured EPCs, the increase in EPC number was most likely attributable to augmented adhesion and differentiation. Indeed, pioglitazone increased EPC adhesion in flow at 1 microM, an effect prevented by PPAR-gamma and beta2-integrin blockade. In contrast, pioglitazone did not promote EPC adhesion at 10 microM; however, increased adhesion became evident by co-incubation with a blocking TGF-beta1 antibody. As determined by ELISA, pioglitazone induced a persistent increase in TGF-beta1 secretion only at 10 microM when a significantly elevated expression of endoglin, the accessory receptor for TGF-beta1, was also observed. Taken together, pioglitazone exerts biphasic effects on the function of isolated EPCs, causing a PPAR-gamma-dependent stimulation at 1 microM and a TGF-beta1-mediated suppression at 10 microM. These results may help to define optimal therapeutic doses of pioglitazone for improving endothelial dysfunction.
...
PMID:Biphasic effect of pioglitazone on isolated human endothelial progenitor cells: involvement of peroxisome proliferator-activated receptor-gamma and transforming growth factor-beta1. 1754 1

An efficient living ring-opening polymerization (ROP) of a permethoxylated epsilon-caprolactone [(OMe)CL] catalyzed by yttrium(III) isopropoxide was developed for the synthesis of degradable protein-resistant polymers [P(OMe)CL]. The lactone monomer was efficiently prepared from a reduced sugar, D-dulcitol. Kinetic studies of the ROP revealed a linear dependence of ln[M]0/[M] on polymerization time as well as a linear correlation between the number-averaged molecular weight (M(n)) and monomer conversion; both support it is a living polymerization. A series of block copolymers of our permethoxylated lactone with epsilon-caprolactone [P(OMe)CL-b-PCL] were synthesized and fully characterized. In thermal analyses only single T(g)s were observed in all the block copolymers, suggesting that P(OMe)CL and PCL blocks are fully miscible. Finally, surface plasmon resonance (SPR) sensograms demonstrated that both P(OMe)CL and the P(OMe)CL-b-PCL block copolymers exhibit excellent resistance to fibrinogen and lysozyme.
...
PMID:Living ring-opening polymerization of a carbohydrate-derived lactone for the synthesis of protein-resistant biomaterials. 1822 Mar 47

Smooth muscle cells (SMC) were cultured for up to 6 days on copolymer films fabricated from a PCL-PEG-PCL block copolymer or P(epsilon-CL-co-D,L-LA)-PEG-P(epsilon-CL-co-D,L-LA), named P(100/0) and P(70/30), respectively. The films were modified by aminolysis using 1,6-hexanediamine, and fibronectin, fibrinogen, or fibrin layers were subsequently immobilized by physisorption or by covalent coupling using imidoester chemistry. Immobilization of all the tested proteins resulted in significantly enhanced cell adhesion on these polymers. Moreover, we found that covalently immobilized proteins supported significantly greater cell proliferation than physisorbed proteins over 6 days. SMC cultured on P(100/0) films modified by covalently attached fibronectin or fibrin layers proliferated at a rate comparable to that observed on control tissue culture polystyrene. The proposed surface modification schemes were much less efficient in improving cell attachment and proliferation on P(70/30) films. However, prewetting P(70/30) with a phosphate buffer prior to aminolysis significantly improved cell numbers following immobilization of fibronectin. Immunostaining of smooth muscle-specific alpha-actin of SMC grown on protein-modified P(100/0) 8 h and 48 h after cell seeding, confirmed preserved SMC phenotype on all modified surfaces.
...
PMID:Enhanced smooth muscle cell adhesion and proliferation on protein-modified polycaprolactone-based copolymers. 1830 10

By sequential ring-opening polymerization of ethylene oxide and epsilon-caprolactone, poly(ethylene oxide) (PEO)-poly(epsilon-caprolactone) (PCL) di-block co-polymers with a phosphoryl choline (PC)-terminated group were synthesized. Using FT-IR, NMR, DSC and SEC, the products were characterized and the results proved the successful synthesis of functionalized di-block co-polymer. After blending the products with polyurethane (PU) and casting the result as film, the PEO segments migrated to the surface of the blend and the PCL segments acted as an anchor to fix the co-polymer on PU matrix, while the PEO segments provided PU the hydrophibility to prevent the fibrinogen adsorption on PU. This specific di-block co-polymer and the method of processing are hoped to be applied in the biomedical field to improve the biocompatibility of polymer materials.
...
PMID:Synthesis and characterization of phosphoryl-choline-capped poly(epsilon-caprolactone)-poly(ethylene oxide) di-block co-polymers and its surface modification on polyurethanes. 1831 62

This work describes the preparation, physicochemical characterization, mechanical properties and in vitro biological properties of two bioresorbable aliphatic segmented poly(esterurethane urea)s (SPEUU) based on poly(epsilon-caprolactone) diol (PCL diol), 1,6-hexamethylene diisocyanate and two novel urea-diol chain extenders. To strengthen the interactions through hydrogen bonding in the hard segments of SPEUU, novel chain extenders containing urea groups were synthesized and used in the SPEUU formulation. The different chemical structures of the chain extenders modulated the phase separation of soft and hard segments, as demonstrated by the thermal behavior. The hard segment association was enhanced using a diurea-diol chain extender. The biological interactions between the obtained materials and blood were studied by in vitro methods. Research on the protein adsorption, platelet adhesion and thrombus formation is presented. Studies of protein adsorption onto polymeric surfaces showed that SPEUU adsorbed more albumin than fibrinogen. Studies on platelet adhesion and thrombus formation of SPEUU-coated coverslips indicated the antithrombogenic behavior of these surfaces. The synthesized SPEUU revealed no signs of cytotoxicity to Chinese hamster ovary cells, showing satisfactory cytocompatibility.
...
PMID:Segmented poly(esterurethane urea)s from novel urea-diol chain extenders: synthesis, characterization and in vitro biological properties. 1835 73

In two-dimensional (2-D) culture systems, we have previously shown that cleaved two-chain high-molecular-weight kininogen (HKa) or its domain 5 induced apoptosis by disrupting urokinase plasminogen activator (uPA) receptor (uPAR)-integrin signal complex formation. In the present study, we used a three-dimensional (3-D) collagen-fibrinogen culture system to monitor the effects of HKa on tube formation. In a 3-D system, HKa significantly inhibited tube and vacuole formation as low as 10 nM, which represents 1.5% of the physiological concentration of high-molecular-weigh kininogen (660 nM), without apparent apoptosis. However, HKa (300 nM) completely inhibited tube formation and increased apoptotic cells about 2-fold by 20-24 h of incubation. uPA-dependent ERK activation and uPAR internalization regulate cell survival and migration. In a 2-D system, we found that exogenous uPA-induced ERK phosphorylation and uPAR internalization were blocked by HKa. In a 3-D system, we found that not only uPA-uPAR association but also the activation of ERK were inhibited by HKa. HKa disrupts the uPA-uPAR complex, inhibiting the signaling pathways, and also inhibits uPAR internalization and regeneration to the cell surface, thereby interfering with uPAR-mediated cell migration, proliferation, and survival. Thus, our data suggest that the suppression of ERK activation and uPAR internalization by HKa contributes to the inhibition of tube formation. We conclude that in this 3-D collagen-fibrinogen gel, HKa modulates the multiple functions of uPAR in endothelial cell tube formation, a process that is closely related to in vivo angiogenesis.
...
PMID:The inhibitory effect of HKa in endothelial cell tube formation is mediated by disrupting the uPA-uPAR complex and inhibiting its signaling and internalization. 1849 8

Fibrinogen has been implicated in atherosclerosis; in part by activating the lipopolysaccharide (LPS) receptor Toll-like receptor 4 (TLR4). The fibrinogen-TLR4 signalling pathway remains uncharacterised. In human macrophages fibrinogen stimulated interleukin (IL)6 expression and ERK (extracellular signal-related kinase) phosphorylation. In HEK293-CD14-MD2 cells expressing TLR4, fibrinogen induced robust phosphorylation of ERK1, p38alpha and JNK and activated transcription factors NFkappaB, Elk-1 and AP-1 (activator protein-1). The net effect of this signalling pathway was a pro-inflammatory response characterised by IL6 and TNFalpha synthesis and increased IL8, matrix metalloproteinase (MMP)1, MMP9, and MCP-1 promoter activity. Two common TLR4 mutations, D299G and T399I, render the receptor LPS hyporesponsive. The effect of fibrinogen on polymorphic variant TLR4s was markedly different; enhancing activation of kinases, transcription factors, cytokine synthesis and promoter activity. This study indicates that fibrinogen activates TLR4, explaining how fibrinogen promotes inflammatory protein expression.
...
PMID:Functional Toll-like receptor 4 mutations modulate the response to fibrinogen. 1869 Mar 51

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.
...
PMID:Relation of cardiorespiratory fitness to inflammatory markers, fibrinolytic factors, and lipoprotein(a) in patients with type 2 diabetes mellitus. 1877 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---