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)

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.
...
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.
...
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.
...
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.
...
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.
...
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.
...
PMID:Mitogen-activated protein kinase-mediated phosphorylation of peroxiredoxin 6 regulates its phospholipase A(2) activity. 1914 Aug 3

The aim of the present study is to explore the signaling pathway associated with Naja naja atra phospholipase A(2) (PLA(2))-induced apoptotic death of human leukemia U937 cells. Degradation of procaspases, production of tBid, loss of mitochondrial membrane potential, and cytochrome c release were observed in PLA(2)-treated cells. PLA(2) treatment increased Fas and FasL protein expression, and upregulated transcription of Fas and FasL mRNA. Upon exposure to PLA(2), ROS generation, p38 MAPK activation, and ERK inactivation were found in U937 cells. Abolition of PLA(2)-induced ROS generation abrogated p38 MAPK activation and upregulation of Fas and FasL expression, but restored ERK activation and viability of PLA(2)-treated cells. Block of p38 MAPK by SB202190 abolished PLA(2)-induced Fas/FasL upregulation and ERK inactivation, but not ROS generation. Activated ERK suppressed p38 MAPK activation and Fas/FasL protein expression. Selective inactivation or overexpression of p38alpha MAPK proved that upregulation of Fas/FasL and ERK inactivation were related to p38alpha MAPK activation. Deprivation of catalytic activity with PLA(2) blocked completely PLA(2)-induced Fas/FasL upregulation. Downregulation of FADD abolished PLA(2)-induced procaspase-8 degradation and rescued viability of PLA(2)-treated cells. Taken together, our results indicate that Fas/FasL upregulation in PLA(2)-treated U937 cells is elicited by ROS-mediated p38alpha MAPK activation and ERK inactivation, and suggest that autocrine Fas/FasL apoptotic mechanism is involved in PLA(2)-induced cell death. J. Cell. Physiol. 219: 642-651, 2009. (c) 2009 Wiley-Liss, Inc.
...
PMID:ROS-mediated p38alpha MAPK activation and ERK inactivation responsible for upregulation of Fas and FasL and autocrine Fas-mediated cell death in Taiwan cobra phospholipase A(2)-treated U937 cells. 1918 May 63

Based on the strong penetration capacity of near infrared lights (NIRs) and different absorption of oxyhemoglobin and deoxyhemoglobin in NIRs region, a novel noninvasive method, with the aid of an airproof-equilibrium apparatus, was developed to determine the oxygen binding-releasing capacity, including oxygen dissociation curve (ODC) and P(50), of the hemoglobin-loaded polymeric nanoparticles (HbP) in this study. The measured ODC of the PLA-PEG HbP was very close to that of the native hemoglobin, and the corresponding P(50) (26.1 mmHg) was also near to the native precursor protein (27.3 mmHg), indicative of the validity of the method proposed. To further verify the method proposed, the oxygen binding-releasing capacity of the HbPs prepared by PCL, PCL-PEG, PLA were also investigated with human blood as control. These results indicated that the method developed here enabled accurate and noninvasive determination of the oxygen binding-releasing capacity of the biodegradable polymeric oxygen carriers.
...
PMID:A noninvasive method for measuring the oxygen binding-releasing capacity of hemoglobin-loaded polymeric nanoparticles as oxygen carrier. 1919 10

We report the synthesis of fully biodegradable polymeric nanoparticles presenting mannose residues at their surface and their interaction with lectins. A simple and versatile method was used to reach the surface functionalization of poly(D,L-lactic acid) (PLA) nanoparticles by mannose moieties: It consists in using an amphiphilic mannosylated poly(ethylene oxide)-b-poly(E-caprolactone) (PEO-b-PCL) diblock copolymer as a bioresorbable surface modifier in a simple nanoprecipitation-evaporation procedure. The size and zeta potential of the nanoparticles were found to depend on the molar copolymer/PLA ratio, demonstrating the influence of the copolymer on the formation of the nanoparticles. The bioavailability of the mannose residues as specific recognition sites on the nanoparticle surface could be demonstrated by a modified enzyme-linked lectin assay (ELLA) using biotin-labeled lectins which interact specifically with alpha-D-mannopyrannoside derivatives. Besides specific interaction by lectin-mannose complex formation, nonspecific adsorption of the proteins on the nanoparticle surface was observed. These results were fully supported by isothermal titration calorimetry experiments which suggested that the balance between specific and nonspecific interactions can be controlled by the amount of glycosylated polymer used for the preparation of the nanoparticles. Such nanoparticles are expected to be specifically recognized by mannose receptors, which are highly expressed in cells of the immune system. The targeting properties of these carrier systems combined with their potential adjuvant effects due to their size in the range of 200-300 nm make them attractive candidates as vaccine delivery systems.
...
PMID:Polyester nanoparticles presenting mannose residues: toward the development of new vaccine delivery systems combining biodegradability and targeting properties. 1920 84

SG1-based poly(d,l-lactide) (PLA) or poly(epsilon-caprolactone) (PCL) macro-alkoxyamines were synthesized and further used as macroinitiators for nitroxide-mediated polymerization (NMP) of 2-hydroxyethyl (meth)acrylate (HE(M)A) to obtain the corresponding PLA- or PCL-PHE(M)A block copolymers. First, a PLA-SG1 macro-alkoxyamine was prepared by 1,2-intermolecular radical addition (IRA) of the MAMA-SG1 (BlocBuilder) alkoxyamine onto acrylate end-capped PLA previously prepared by ring-opening polymerization. The NMP of HEA monomer from the PLA-SG1 macro-alkoxyamine appeared to be well controlled in the presence of free SG1 nitroxide, contrary to that of HEMA. In the latter case, adjustable molecular weights could be obtained by varying the HEMA to macro-alkoxyamine ratio. The versatility of our approach was then further applied to the preparation of PHEMA-b-PCL-b-PHEMA copolymers from a alpha,omega-di-SG1 functionalized PCL macro-alkoxyamine previously obtained from a PCL diacrylate by IRA. Preliminary studies of neuroblast cultures on these PCL-based copolymer films showed acceptable cyto-compatibility, demonstrating their potential for nerve repair applications.
...
PMID:Convenient access to biocompatible block copolymers from SG1-based aliphatic polyester macro-alkoxyamines. 1939 59


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

---