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)

To become fertilization competent, mammalian sperm undergo changes in the female reproductive tract termed capacitation. Capacitation correlates with an increase in tyrosine phosphorylation; however, less is known about the role of serine/threonine phosphorylation in this process. Proline-directed phosphorylation is one of the major regulatory phosphorylation events in many cellular processes such as cell proliferation and differentiation. Using mitotic phosphoprotein monoclonal-2 (MPM-2) antibody in this study, we observed that several mouse sperm proteins in the range of 70-250 kDa underwent increased serine/threonine-proline phosphorylation during capacitation. In contrast to the time course of tyrosine phosphorylation, proline-directed phosphorylation could be observed at shorter time points of sperm incubation, and it was found to be independent of NaHCO(3) and adenosine 3'5'-cyclic monophosphate (cAMP). Similar to the regulation of the increase in tyrosine phosphorylation, cholesterol acceptors such as bovine serum albumin (BSA) or 2-hydroxypropyl-beta-cyclodextrin (2-OH-propyl-beta-CD) were essential for the regulation of proline-directed phosphorylation in mouse sperm. Furthermore, it was also found to be BSA dependent in human sperm. Among proline-directed kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) is present in mammalian sperm; nevertheless, U0126 and PD098059, two inhibitors of the ERK pathway, did not block this phosphorylation in mouse sperm. In conclusion, capacitation is associated with an increase in proline-directed phosphorylation linked to cholesterol efflux in the sperm.
...
PMID:Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation. 1705 Jul 74

Growth factors are increasingly employed to promote tissue regeneration with various biomaterial scaffolds. In vitro release kinetics of protein growth factors from tissue engineering scaffolds are often investigated in aqueous environment, which is significantly different from in vivo environment. This study investigates the release of model proteins with net-positive (histone) and net-negative charge (bovine serum albumin, BSA) from various scaffolding surfaces and from encapsulated microspheres in the presence of ions, proteins, and cells. The release kinetics of proteins in media with varying concentrations of ions (NaCl) suggests stronger electrostatic interaction between the positively charged histone with the negatively charged substrates. While both proteins released slowly from hydrophobic PCL surfaces, plasma etching resulted in rapid release of BSA, but not histone. Interestingly, although negatively charged BSA released readily from negatively charged collagen (col), BSA released slowly from col-coated PCL scaffolds. Such electrostatic interaction effects were abolished in the presence of serum proteins and cells as evidenced by the rapid release of proteins from col-coated scaffolds. To achieve sustained release in the complex environment of serum proteins and cells, the model proteins were encapsulated into poly(D,L-lactic-co-glycolic acid) (PLGA) microspheres, which were embedded within col-coated PCL scaffolds. Protein release from microspheres was modulated by changing the lactide-to-glycolide ratio of PLGA polymer. BSA adsorbed to col released faster than histone encapsulated in microspheres in the presence of serum and cells. Collectively, the data suggest that growth factor release is highly influenced by scaffold surface and the presence of ions, proteins, and cells in the media. Strategies to deliver multiple growth factors and studies which investigate their release should consider these important variables.
...
PMID:Modulation of protein delivery from modular polymer scaffolds. 1718 36

This study aimed to determine the effects of advanced glycation end products (AGEs) on endothelial cytoskeleton morphology and permeability, and to detect the underlying signaling mechanisms involved in these responses. Cultured endothelial cells (ECs) were exposed to AGE-modified human serum albumin (AGE-HSA), and EC cytoskeletal changes were evaluated by observing fluorescence of F-actin following ligation with labeled antibodies. Endothelial permeability was detected by measuring the flux of TRITC-albumin across the EC monolayers. To explore the signaling pathways behind AGE-induced EC alteration, ECs were treated with either soluble anti-AGE receptor (RAGE) IgG, or the MAPK inhibitors PD98059 and SB203580 before AGE-HSA administration. To further elucidate possible involvement of the ERK and p38 pathways in AGE-induced EC changes, adenovirus-carried recombinant constitutive dominant-negative forms of upstream ERK and p38 kinases, namely MEK1(A) and MKK6b(A), were pre-infected into ECs 24 h prior to AGE-HSA exposure. AGE-HSA induced actin cytoskeleton rearrangement, as well as EC hyperpermeability, in a dose and time-dependent manner. The effects were attenuated in cells pretreated with anti-RAGE IgG, PD98059 or SB203580, respectively. EC pre-infection with MEK1(A) and MKK6b(A) also alleviated the effect of AGEs. Furthermore, adenovirus-mediated administration of activated forms of either MEK1 or MKK6b alone induced rearrangement of F-actin and hyperpermeability. The results indicate that ERK and p38 MAPK play important roles in the mediation of AGE-induced EC barrier dysfunction associated with morphological changes of the F-actin.
...
PMID:Advanced glycation end products induce actin rearrangement and subsequent hyperpermeability of endothelial cells. 1959 96

An MPEG-PCL diblock copolymer was synthesized as an in situ gel carrier, and its phase transition behavior in aqueous solutions was examined. For comparison, aqueous solutions of Pluronic F-127, a widely used injectable gel-forming solution, were also studied. Both MPEG-PCL copolymer and Pluronic aqueous solutions were sols at room temperature. As the temperature was increased above room temperature, the diblock copolymer and Pluronic solutions underwent a sol-to-gel phase transition, which manifested as an increase in viscosity indicative of the formation of a gel. All of the copolymer solutions became gels at body temperature, although the gel viscosity increased with the increasing concentration of the MPEG-PCL diblock copolymer in the solution. In in vitro experiments, in which the gels were exposed to PBS, the MPEG-PCL gels maintained their structural integrity for more than 28 days, whereas the Pluronic gel disappeared within 2 days. The same results were observed when the polymer solutions were subcutaneously injected into rats. The MPEG-PCL gels maintained their structural integrity longer than 30 days, while the Pluronic gel could not be observed after 2 days. The ability of the gels as drug carriers was studied by measuring the release of fluorescein isothiocyanate-labeled bovine serum albumin (BSA-FITC) from MPEG-PCL diblock copolymer gels in vitro as well as in vivo. In vitro, BSA release was sustained above 20 days, with a greater release at lower diblock copolymer concentration; by contrast, Pluronic gels exhibited almost complete release of BSA-FITC within 1 day. When the BSA-FITC-loaded diblock copolymer and Pluronic solutions were subcutaneously injected into rats, they immediately transformed into a gel. In vivo, sustained release of BSA-FITC over 30 days was observed from the MPEG-PCL gel, whereas BSA-FITC release from the Pluronic gel ceased within 3 days. Collectively, the present findings show that MPEG-PCL diblock copolymer solutions are thermo-responsive and maintain their structural integrity under physiological conditions, indicating that they are suitable for use as injectable drug carriers.
...
PMID:In vitro and in vivo release of albumin using a biodegradable MPEG-PCL diblock copolymer as an in situ gel-forming carrier. 1732 78

Size of the microparticle and integrity of the released protein are two crucial factors which dictate the success of any protein or vaccine delivery system. The primary objective was to optimize bovine serum albumin (BSA) loaded polycaprolactone/maltodextrin (PCL/MD) microparticles in terms of its size and the hydrodynamic diameter of the released protein. The effect of size determining formulation process variables (SDFPV) of microparticles on the hydrodynamic diameter of protein antigen was determined. The SDFPV were optimized by a compromise between the microparticle size and the relative hydrodynamic stability of protein released from it. Percentage of secondary structure of the protein released from the optimized formulation as determined by circular dichroism spectra along with SELCON software was also similar to that of native BSA suggesting the potential of PCL /MD microparticles for protein or vaccine delivery.
...
PMID:Formulation of maltodextrin entrapped in polycaprolactone microparticles for protein and vaccine delivery: effect of size determining formulation process variables of microparticles on the hydrodynamic diameter of BSA. 1749 89

The purpose of this study was to design an in vitro experiment that can assess the stability of polymeric micellar formulations of hydrophobic drugs such as cyclosporine A (CyA) in blood, and predict the in vivo performance of the examined delivery system. Poly(ethylene oxide)-block-poly(epsilon-caprolactone) (PEO-b-PCL) copolymers were assembled to polymeric nano-containers for the physical encapsulation of CyA by a co-solvent evaporation method using different loading conditions. CyA-loaded micelles were prepared and compared to commercially available intravenous formulation of CyA (Sandimmune) for in vitro release, protein binding, and pharmacokinetic parameters in Sprague-Dawley rats. The unbound fraction (fu) of CyA was determined using an erythrocyte vs. plasma and buffer partitioning technique. Different polymeric micellar formulations of CyA did not show any significant difference in CyA release when dialyzed against bovine serum albumin. The fu experiments, however, revealed a significant decrease in the fu of the loaded drug with an increase in the drug/polymer loading ratio, while the fu of all micellar formulations were significantly lower than Sandimmune. The pharmacokinetic study showed that fu of CyA in each formulation correlated with its in vivo performance determined by pharmacokinetic parameters: the lower fu of the formulation, translated to a higher area under the concentration versus time curve (AUC), and a lower clearance (CL) and volume of distribution (Vd). In conclusion, determination of the unbound fraction of encapsulated drug can be used to predict the in vivo stability of polymeric micellar nano-containers. PEO-b-PCL micelles containing higher CyA-loaded levels are shown to be more stable changing the pharmacokinetics of the encapsulated CyA to a higher extent.
...
PMID:A novel use of an in vitro method to predict the in vivo stability of block copolymer based nano-containers. 1764 7

Drug delivery applications using biodegradable polymeric microspheres are becoming an important means of delivering therapeutic agents. The aim of this work was to modulate the microporosity of poly(epsilon-caprolactone) (PCL) microcarriers to control protein loading capability and release profile. PCL microparticles loaded with BSA (bovine serum albumin) have been de novo synthesized with double emulsion solvent evaporation technique transferred and adapted for different polymer concentrations (1.7 and 3% w/v) and stabilizer present in the inner aqueous phase (0.05, 0.5 and 1% w/v). SEM (scanning electron microscope) and CLSM (confocal laser scanning microscope) analysis map the drug distribution in homogeneously distributed cavities inside the microspheres with dimensions that can be modulated by varying double emulsion process parameters. The inner structure of BSA-loaded microspheres is greatly affected by the surfactant concentration in the internal aqueous phase, while a slight influence of polymer concentration in the oil phase was observed. The surfactant concentration mainly determines microspheres morphology, as well as drug release kinetics, as confirmed by our in-vitro BSA release study. Moreover, the entrapped protein remained unaltered during the protein encapsulation process, retaining its bio-activity and structure, as shown through a dedicated gel chromatographic analytical method.
...
PMID:Engineering of poly(epsilon-caprolactone) microcarriers to modulate protein encapsulation capability and release kinetic. 1791 22

Free radical production is increased during diabetes. Serum albumin is a major antioxidant agent, and structural modification of albumin induced by glucose or free radicals impairs its antioxidant properties. Therefore the aim of the present study was to compare the antioxidant capacities and structural changes in albumin in patients with T2DM (Type 2 diabetes mellitus) treated with MET (metformin) or SU (sulfonylureas) and in healthy control subjects. Structural changes in albumin were studied by fluorescence quenching in the presence of acrylamide. Albumin thiols and fructosamines, reflecting oxidized and glycation-induced changes in serum albumin respectively, were assessed. Structural changes in albumin were demonstrated by a significant decrease in fluorescence quenching in patients with T2DM, with patients treated with MET exhibiting a significant difference in the conformation of albumin compared with patients treated with SU. Oxidation, resulting in a significant decrease in thiol groups and plasma total antioxidant capacity, and glycation, associated with a significant increase in fructosamines, were both found when comparing healthy control subjects with patients with T2DM. When patients treated with MET were compared with those treated with SU, oxidative stress and glycation were found to be significantly lower in MET-treated patients. In conclusion, patients with T2DM have a decrease in the antioxidant properties of serum albumin which may aggravate oxidative stress and, thus, contribute to vascular and metabolic morbidities. Moreover, a significant protection of albumin was found in patients with T2DM treated with MET.
...
PMID:Impairment of the antioxidant properties of serum albumin in patients with diabetes: protective effects of metformin. 1792 77

Hydrogels with pH-sensitive poly(acrylic acid) (PAAc) chains and biodegradable acryloyl-poly(-caprolactone)-2-hydroxylethyl methacrylate (AC-PCL-HEMA) chains were designed and synthesized. The morphology of hydrogel was observed by scanning electron microscopy. The degradation of the hydrogel in the presence of Pseudomonas lipase was studied. The in vitro release of bovine serum albumin from the hydrogel was investigated. Cytotoxicity study shows that the AC-PCL-HEMA/AAc copolymer exhibits good biocompatibility. Cell adhesion and migration into the hydrogel networks were evaluated by using different cell lines. The hydrogel with a lower cross-linking density and a larger pore size exhibited a better performance for cells migration.
...
PMID:Biodegradable and pH-sensitive hydrogels for cell encapsulation and controlled drug release. 1830 10

A new class of supramolecular and biomimetic glycopolymer/poly(epsilon-caprolactone)-based polypseudorotaxane/glycopolymer triblock copolymers (poly(D-gluconamidoethyl methacrylate)-PPR-poly(D-gluconamidoethyl methacrylate), PGAMA-PPR-PGAMA), exhibiting controlled molecular weights and low polydispersities, was synthesized by the combination of ring-opening polymerization of epsilon-caprolactone, supramolecular inclusion reaction, and direct atom transfer radical polymerization (ATRP) of unprotected D-gluconamidoethyl methacrylate (GAMA) glycomonomer. The PPR macroinitiator for ATRP was prepared by the inclusion complexation of biodegradable poly(epsilon-caprolactone) (PCL) with alpha-cyclodextrin (alpha-CD), in which the crystalline PCL segments were included into the hydrophobic alpha-CD cavities and their crystallization was completely suppressed. Moreover, the self-assembled aggregates from these triblock copolymers have a hydrophilic glycopolymer shell and an oligosaccharide threaded polypseudorotaxane core, which changed from spherical micelles to vesicles with the decreasing weight fraction of glycopolymer segments. Furthermore, it was demonstrated that these triblock copolymers had specific biomolecular recognition with concanavalin A (Con A) in comparison with bovine serum albumin (BSA). To the best of our knowledge, this is the first report that describes the synthesis of supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids and the fabrication of glucose-shelled and oligosaccharide-threaded polypseudorotaxane-cored aggregates. This hopefully provides a platform for targeted drug delivery and for studying the biomolecular recognition between sugar and lectin.
...
PMID:Supramolecular and biomimetic polypseudorotaxane/glycopolymer biohybrids: synthesis, glucose-surfaced nanoparticles, and recognition with lectin. 1831 28


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

---