Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.12.2 (MEK)
 18,161 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This work focuses on the photocatalytic oxidation of gaseous methyl ethyl ketone chosen as a typical indoor air pollutant. Two types of TiO coatings were prepared and deposited on glass plates: one using the commercial Degussa P25 TiO2 and the other one by sol-gel method. The first objective of this study was to compare different ways of preparing thin films of sol-gel TiO2 coated on glass plates, taking into account their general aspect and their photocatalytic efficiency. Several parameters were tested, such as the stabilising agent, the glass type of the support, the number of coatings and the calcination temperature. One of the synthesised materials was then kept to carry out the following study. The study aimed to assess the influence of TiO2 coating types on the effect of water vapour. This was achieved by performing MEK photocatalytic degradation kinetics under two levels of humidity at a fixed temperature. Experimental results were then modelled by the Langmuir-Hinshelwood equation. The obtained parameters gave specific trends in function of the considered catalyst. The second part of this work was to identify MEK degradation byproducts during its photocatalytic oxidation. The main detected intermediate was acetaldehyde, followed by methyl formate. A MEK degradation pathway was then proposed.
Water Sci Technol 2006
PMID:Photocatalytic oxidation of methyl ethyl ketone over sol-gel and commercial TiO2 for the improvement of indoor air. 1686 80

The MEK-mitogen-activated protein kinase (MAPK) signal transduction pathway is involved with numerous cellular processes including cell growth and differentiation. Phosphorylation of MAPK (pMAPK) by MEK results in activation of this pathway. In various solid tumors, the MEK-MAPK pathway is constitutively active; therefore inhibition of this pathway may provide a therapeutic strategy for treating cancer. The objective of this study was to determine the extent and duration of inhibition of pMAPK in selected normal tissues in rats following single oral or intravenous (IV) doses of the novel MEK inhibitor, PD0325901. Male Sprague-Dawley rats (9/group) received either single oral (PO) or IV doses of PD0325901 at 10, 30, or 100 mg/kg (60, 180, and 600 mg/m(2), respectively). Controls received vehicle alone which was aqueous 0.5% hydroxypropylmethyl-cellulose/0.2% Tween 80 for PO dosing and 20% beta-cyclodextran sulfobutyl ether in water (w:v) for IV dosing. Animals (3/group/day) were euthanized on Days 2, 3, and 4, at approximately 24, 48, and 72 h after dosing, respectively. The effects on pMAPK in liver and lung were determined by Western blot analysis and compared with plasma PD0325901 levels. Satellite animals (6/dose/route) received single PO or IV doses and serial blood samples were collected for determination of toxicokinetic parameters of PD0325901 and its major metabolite. In general, systemic exposure to PD0325901 was comparable between routes of administration due to high PO bioavailability (56-109%). Plasma area under the concentration-time curve values of the pharmacologically inactive carboxylic acid metabolite ranged from 18 to 40% of PD0325901. Clinical signs of toxicity occurred at 100 mg/kg PO or IV, indicating the maximum-tolerated dose had been achieved. On Day 2, pMAPK was inhibited 57-95% in liver and 86-99% in lung at all doses, irrespective of route of administration. On Day 3, lung pMAPK remained inhibited 75-91% at all IV doses and by 88% after the 100-mg/kg PO dose. Liver pMAPK remained inhibited 79 and 91% on Day 3 after 100 mg/kg by IV and PO doses, respectively. On Day 4, liver pMAPK was still inhibited 66% after the 100-mg/kg PO dose. The EC(50) and EC(90) plasma drug levels for inhibition of lung pMAPK were calculated to be 20 and 99 ng/ml, respectively. Liver pMAPK levels were inhibited at least 50% at plasma PD0325901 concentrations > or =50 ng/ml. In conclusion, single PO or IV doses of PD0325901 resulted in dose-dependent inhibition of pMAPK in liver and lung. Inhibition of pMAPK in liver was comparable between routes of administration at < or =30 mg/kg, whereas inhibition of pMAPK in lung occurred for a longer duration following IV administration. Measurement of pMAPK in normal tissues served as a means for assessing the pharmacologic activity of PD0325901 and should be included in toxicity studies to evaluate toxicity-pharmacology relationships.
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PMID:Pharmacodynamic and toxicokinetic evaluation of the novel MEK inhibitor, PD0325901, in the rat following oral and intravenous administration. 1694 49

The effect of particle size on the reactivity of hexyltrimethoxysilane (C6S) with the particle surface was studied by using silica nanoparticles (SNPs) with different diameters (30 or 200 nm). In case of 30-nm SNPs, a large amount of isolated silanol was observed. On the other hand, in the case of 200-nm SNPs, the amount of hydrogen bonded silanol and hydrogen bonded water molecules at the surface of the SNPs increased. Since the hydrogen bonded silanol and the hydrogen bonded water enhanced the reaction of C6S with SNPs, the chemisorbed C6S on 200-nm SNPs was larger than that on 30-nm SNPs. Furthermore, the effects of surface modification on the dispersion stability in MEK were studied using viscosity measurements and surface force measurements by the AFM colloid probe method. The viscosity of the dilute SNPs/MEK suspension did not change by the chemisorptions of C6S; however, the viscosity of dense suspension reduced effectively by surface modification. It was estimated that the suspension viscosity reduced effectively when the mean particle surface distance in the suspension was near to the distance where the repulsive force appeared by the surface force measurements using the colloid probe AFM.
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PMID:Effect of particle size on surface modification of silica nanoparticles by using silane coupling agents and their dispersion stability in methylethylketone. 1718 53

Stomata are specialized epidermal structures that regulate gas (CO(2) and O(2)) and water vapor exchange between plants and their environment. In Arabidopsis thaliana, stomatal development is preceded by asymmetric cell divisions, and stomatal distribution follows the one-cell spacing rule, reflecting the coordination of cell fate specification. Stomatal development and patterning are regulated by both genetic and environmental signals. Here, we report that Arabidopsis MITOGEN-ACTIVATED PROTEIN KINASE3 (MPK3) and MPK6, two environmentally responsive mitogen-activated protein kinases (MAPKs), and their upstream MAPK kinases, MKK4 and MKK5, are key regulators of stomatal development and patterning. Loss of function of MKK4/MKK5 or MPK3/MPK6 disrupts the coordinated cell fate specification of stomata versus pavement cells, resulting in the formation of clustered stomata. Conversely, activation of MKK4/MKK5-MPK3/MPK6 causes the suppression of asymmetric cell divisions and stomatal cell fate specification, resulting in a lack of stomatal differentiation. We further establish that the MKK4/MKK5-MPK3/MPK6 module is downstream of YODA, a MAPKKK. The establishment of a complete MAPK signaling cascade as a key regulator of stomatal development and patterning advances our understanding of the regulatory mechanisms of intercellular signaling events that coordinate cell fate specification during stomatal development.
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PMID:Stomatal development and patterning are regulated by environmentally responsive mitogen-activated protein kinases in Arabidopsis. 1725 59

Ginseng has been shown to inhibit cancer cell proliferation and tumor growth, however the mechanisms underlying this inhibition have yet to be elucidated. An inhibitory effect of hot water-extracted American ginseng (Panax quinquefolius L.) root on cell proliferation was demonstrated using MCF-7 human breast cancer cells treated with a wide concentration range of the ginseng extract (GE) for 6 days. The effects of GE were concentration-dependent with an IC50 of 0.49 microg/microl and the minimum exposure time to elicit an inhibitory response was 24 hours. Using an antibody microarray, it was determined that several key cell survival proteins were altered in GE-treated cells, including several members of the mitogen-activated protein kinase (MAPK) family. A GE-induced decrease in phospho-MEK1/2 and -ERK1/2 and an increase in phospho-Raf-1 were observed and verified using Western blot analysis. Furthermore, mRNA and protein expression of the Raf-1 kinase inhibitor protein (RKIP) was shown to be transiently, yet significantly, upregulated following GE treatment. These results suggest that American ginseng may act to inhibit breast cancer cell proliferation by increasing the expression of RKIP, resulting in inhibition of the MAPK pathway. This novel mechanism has implications in the potential prevention and treatment of breast cancer.
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PMID:American ginseng (Panax quinquefolius L.) extract alters mitogen-activated protein kinase cell signaling and inhibits proliferation of MCF-7 cells. 1740 73

Recent studies indicate that iron (Fe) is involved in neurotoxicity caused by inorganic lead (Pb). We studied the role of Fe in the effects Pb-induced cerebral apoptosis during rat development and to explore its possible regulatory mechanism. In the present study, weanling male Sprague-Dawley rats were randomly divided into four groups. Three groups of rats received 400 microg/mL Pb acetate solution in drinking water, among which two of the groups were concurrently given 20mg/kg and 40mg/kg FeSO(4) solution, respectively, as the low and high Fe group, for 6 weeks. The Fe doses were administered orally by gavage every other day according to animal body weight. For the control group, Na acetate with an acetate concentration equivalent to the high dose of Pb acetate was prepared in the same manner. At the end of the study, exposure to Pb in drinking water significantly promoted internucleosomal DNA fragmentation, enhanced the percentage of TUNEL-positive cells and increased the caspase-3 activities in cortex as compared to the controls. At the same time, it did cause a significant decrease in cortex Fe concentrations. Concomitant supplement with different dose Fe appeared to restore brain Fe level to the normal level. Although the low dose of Fe restored brain Pb level to the normal level and the high dose of Fe did not, both of them reduced the formation of DNA fragments, showed few TUNEL-positive cells with yellow nuclei and inhibited Pb-induced procaspase-3 degradation. Western blot showed that exposure to Pb caused a significant elevation in the phosphorylation of ERK1/2, JNK1/2, and Elk-1. Low Fe supplemental treatment suppressed the phosphorylation of ERK1/2 and JNK1/2 but not Elk-1. Interestingly, high Fe treatment slightly suppressed the phosphorylation of JNK1/2, but significantly elevated the phosphorylation of ERK1/2 and Elk-1. Collectively, the current study suggests that supplementation of Fe during Pb treatment prevents against cytotoxicity and apoptosis induced by Pb insults, in which MAPK pathways play an important role in Pb-induced cerebral apoptosis by activating the MEK-ERK pathway that suppresses JNK signaling.
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PMID:Iron supplementation protects against lead-induced apoptosis through MAPK pathway in weanling rat cortex. 1756 Jun 53

Angiogenesis is important for promoting cardiovascular disease, wound healing, and tissue regeneration. We investigated the effects of Korean red ginseng water extract (KRGE) on angiogenesis and its underlying signal mechanism. KRGE increased in vitro proliferation, migration, and tube formation of human umbilical vein endothelial cells, as well as stimulated in vivo angiogenesis without increasing VEGF expression. KRGE-induced angiogenesis was accompanied by phosphorylation of ERK1/2, phosphatidylinositol 3-kinase (Akt), and endothelial nitric oxide synthase (eNOS) as well as an increase in NO production. Inhibition of PI3K activity by wortmannin completely inhibited KRGE-induced angiogenesis and phosphorylation of Akt, ERK1/2, and eNOS, indicating that PI3K/Akt activation is an upstream event of the KRGE-mediated angiogenic pathway. The MEK inhibitor PD98059 blocked KRGE-induced ERK1/2 phosphorylation without affecting Akt and eNOS activation. However, the eNOS inhibitor N(G)-monomethyl-L-arginine effectively inhibited tube formation, but partially blocked proliferation and migration as well as ERK phosphorylation, without altering Akt and eNOS activation, revealing that the eNOS/NO pathway is partially involved in ERK1/2 activation. This study demonstrated that KRGE stimulates in vitro and in vivo angiogenesis through the activation of the PI3K/Akt-dependent ERK1/2 and eNOS signal pathways and their cross talk.
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PMID:Water extract of Korean red ginseng stimulates angiogenesis by activating the PI3K/Akt-dependent ERK1/2 and eNOS pathways in human umbilical vein endothelial cells. 1782 19

One of the major characteristics of human skin photoaging induced by ultraviolet (UV) radiation is the dehydration of the skin. Water movement across plasma membrane occurs via diffusion through lipid bilayer and via aquaporins (AQPs). We find that UV induces aquaporin-3 (AQP3) down-regulation in human skin keratinocytes. MEK/ERK inhibitors PD98059 and U0126 inhibit UV-induced down-regulation of AQP3. Antioxidant N-acetyl-L-cysteine or NAC blocks UV-induced MEK/ERK activation and down-regulation of AQP3. All-trans retinoic acid or atRA, while alone inducing AQP3 expression, attenuates UV-induced down-regulation of AQP3 and water permeability. Using special inhibitors, we find that activation of EGFR and inhibition on ERK activation are involved in atRA's protective effects against UV-induced AQP3 down-regulation. Using specific AQP3's water transport inhibitors and siRNA knockdown, we observe that AQP3 is involved in cell migration and in vitro wound healing. UV-induced AQP3 down-regulation results in reduced water permeability, decreased cell migration, and delayed wound healing, which are attenuated by atRA pretreatment. We conclude that atRA protects against UV-induced down-regulation AQP3 and decrease in water permeability, reduction in cell migration and delayed in vitro wound healing via trans-activation of EGFR and inhibition on ROS-mediated MEK/ERK pathway. This novel finding provides evidence to support possible involvement of AQP3 in UV induced skin dehydration.
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PMID:All-trans retinoic acid attenuates ultraviolet radiation-induced down-regulation of aquaporin-3 and water permeability in human keratinocytes. 1806 29

For understanding the actions of magnesium formulations, magnesium oxide and magnesium sulfate as a constituent of antacid, in the gastrointestinal tract, the effect of magnesium ion on the water channel aquaporin 3 (AQP3) known to be permeable mainly to water and glycerol was investigated in Caco-2 cells. The mRNA and protein of aquaporin 3 were detected by real-time RT-PCR and Western blotting, respectively, and found to increase significantly after treatment with magnesium acetate. Inhibitors for signal transducers, MDL-12330A, H-89, U0126, and Ro 31-8220, were shown to repress the increase in expression of the mRNA. A luciferase reporter vector containing bp -1382 to -12 of the 5'-flanking region of the aquaporin 3 gene was constructed for a reporter gene assay. The luciferase activity in transfectants increased on treatment with magnesium acetate. Serial deletion constructs revealed two regions responsible for the magnesium ion-mediated activation, one between bps -404 and -190, and the other between bps -190 and -82. siRNA for the cAMP response element-binding protein (CREB) sequence located between bp -404 and -190 counteracted the magnesium ion-mediated activation of aquaporin 3 transcription. These results suggest that signal transducers, adenylyl cyclase, protein kinase A (PKA), mitogen-activated protein kinase 1/2 (MEK1/2), and mitogen- and stress-activated protein kinase 1 (MSK1), were involved in the signaling pathway for regulating transcription of the aquaporin 3 gene and CREB is one of the transcriptional regulators for aquaporin 3 gene expression mediated by magnesium ion.
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PMID:Regulation of aquaporin 3 expression by magnesium ion. 1849 15

Vasopressin regulates water excretion through effects on the renal collecting duct. Vasopressin signaling in the inner medullary collecting duct (IMCD) is mediated by V2 receptor occupation coupled to the generation of cyclic AMP. Here, we employ a "systems" approach to analysis of vasopressin signaling. The objective is to investigate roles of activation of the Akt and ERK1/2 MAP kinase pathways, as well as Ca2+ mobilization, in IMCD cells isolated from rat kidney. The V2 receptor-selective vasopressin analog dDAVP increased the state of Akt activation (increased phosphorylation at T308 and S473) and decreased the state of ERK1/2 activation (decreased phosphorylation at T202 and Y204). Akt activation was blocked by an inhibitor of PI3K, LY294002. In microdissected IMCD segments, nonperiodic spike-like increases in intracellular Ca2+ (FLUO-4) were accelerated by vasopressin. Chelation of Ca2+ or calmodulin inhibition markedly decreased Akt phosphorylation. Decreased ERK1/2 phosphorylation was associated with a decrease in MEK1/2 phosphorylation and an increase in c-Raf phosphorylation at S259 (an inhibitory site). Based on the current findings integrated with previous findings in the IMCD, we now report a 33-node vasopressin signaling network involved in vasopressin regulation of IMCD function.
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PMID:Akt and ERK1/2 pathways are components of the vasopressin signaling network in rat native IMCD. 1866 81


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