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

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Query: EC:2.7.10.2 (focal adhesion kinase)
44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The determination of moisture content in coal and coke is required for the accurate reporting of physical and chemical constituents on a dry mass basis. Interlaboratory comparisons are reported on a dry mass basis and require reproducible assessments of moisture content to minimize differences among laboratories. Comparability between laboratories is necessary to ensure equity in trade and to avoid costly disputes between buyer and seller. Moisture loss was measured as mass (M) loss as a function of time (t) at constant temperature in a dynamic inert nitrogen atmosphere on 10 SRM coals (7 bituminous and 3 subbituminous) and 4 SRM cokes. Three different patterns of mass-loss were observed-ideal (dM/dt = 0), and two anomalous behaviors, negative deviation (dM/ dt < 0) and positive deviation (dM/dt > 0). Bituminous coals with lower moisture (1-4%) and volatile content (33-38%) tend to display either ideal or positive behavior while subbituminous coals with higher moisture (12-17%) and volatile content (41-47%) display negative behavior. The identification of these different mass-loss patterns demonstrates the potential for method bias depending on the drying end-point definition (ASTM and LECO) used.
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PMID:Observations of anomalous mass-loss behavior in SRM coals and cokes on drying. 1217 40

Bisphosphonates are potent inhibitors of osteoclast function widely used to treat conditions of excessive bone resorption, including tumor bone metastases. Recent evidence indicates that bisphosphonates have direct cytotoxic activity on tumor cells and suppress angiogenesis, but the associated molecular events have not been fully characterized. In this study we investigated the effects of zoledronate, a nitrogen-containing bisphosphonate, and clodronate, a non-nitrogen-containing bisphosphonate, on human umbilical vein endothelial cell (HUVEC) adhesion, migration, and survival, three events essential for angiogenesis. Zoledronate inhibited HUVEC adhesion mediated by integrin alphaVbeta3, but not alpha5beta1, blocked migration and disrupted established focal adhesions and actin stress fibers without modifying cell surface integrin expression level or affinity. Zoledronate treatment slightly decreased HUVEC viability and strongly enhanced tumor necrosis factor (TNF)-induced cell death. HUVEC treated with zoledronate and TNF died without evidence of enhanced annexin-V binding, chromatin condensation, or nuclear fragmentation and caspase dependence. Zoledronate inhibited sustained phosphorylation of focal adhesion kinase (FAK) and in combination with TNF, with and without interferon (IFN) gamma, of protein kinase B (PKB/Akt). Constitutive active PKB/Akt protected HUVEC from death induced by zoledronate and TNF/IFNgamma. Phosphorylation of c-Src and activation of NF-kappaB were not affected by zoledronate. Clodronate had no effect on HUVEC adhesion, migration, and survival nor did it enhanced TNF cytotoxicity. Taken together these data demonstrate that zoledronate sensitizes endothelial cells to TNF-induced, caspase-independent programmed cell death and point to the FAK-PKB/Akt pathway as a novel zoledronate target. These results have potential implications to the clinical use of zoledronate as an anti-angiogenic or anti-cancer agent.
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PMID:Zoledronate sensitizes endothelial cells to tumor necrosis factor-induced programmed cell death: evidence for the suppression of sustained activation of focal adhesion kinase and protein kinase B/Akt. 1293 98

The aim of this study was to investigate the cytotoxic activity of the third-generation nitrogen-containing bisphosphonate zoledronic acid (ZOL) as a single agent, and in combination with clinically relevant anticancer drugs, in a panel of human osteogenic sarcoma cell lines (HOS, BTK-143, MG-63, SJSA-1, G-292, and SAOS2). We found that ZOL, when used alone, reduced cell number in a dose- and time-dependent manner, due either to cell cycle arrest in S-phase or to the induction of apoptosis. In the sensitive HOS, BTK-143, and G-292 cell lines, genomic DNA fragmentation and morphological changes characteristic of apoptosis were evident, and cells became nonadherent. Induction of apoptosis in osteosarcoma cells by ZOL was associated with caspase activation. However, coaddition of the broad-spectrum caspase inhibitors, z-VAD-fmk, Boc-D-fmk, or the caspase-3-specific inhibitor z-DEVD fmk, failed to protect these cells from ZOL-induced apoptosis. Our data support a ZOL-specific induction of cell apoptosis that involves cell detachment (anoikis), and in which caspase activation occurs secondarily to, and is redundant as a mediator of cell death. The addition of geranylgeraniol, an intermediate of the mevalonate pathway, suppressed the ZOL-induced apoptosis, suggesting that the cytotoxic effects of ZOL in osteosarcoma cells were mediated by the mevalonate pathway. While treatment of osteosarcoma cells with the chemotherapeutic agents doxorubicin or etoposide decreased cell viability, combination of these agents with ZOL did not significantly augment apoptosis in any of the cell lines tested. These observations suggest that ZOL has direct effects on the proliferation and survival of osteosarcoma cells in vitro, which has implications for future therapy of osteosarcoma.
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PMID:Induction of cell death of human osteogenic sarcoma cells by zoledronic acid resembles anoikis. 1449 55

Sugars accumulation and fructokinase activity during satsuma mandarin fruit development in relation to the effect of extra nitrogenous fertilizer on the activity and expression of fructokinase were studied. The results exhibited that fructokinase activity in the tissues of edible and peel decreased during fruit development, which coincided with the accumulation of sugars, while the contents of sucrose and glucose decreased, and the activity of the enzyme increased in peel tissues of ripened fruit. After fertilizing with extra urea, the ratios of sucrose and fructose decreased in ripe fruit, while that of glucose increased compared to the control. The activity of fructokinase presented on a protein basis increased in treated fruit. Northern analysis confirmed that extra nitrogenous fertilizer enhanced the expression of Cufrk1 at the late stage of fruit development, but had no effect on Cufrk2. The results suggest that the two different genes of citrus FRK may play distinct roles in sink metabolism and Cufrk1-encoded fructokinase protein could be induced by fertilization with extra nitrogen.
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PMID:[The relationship of fructokinase and sugar accumulation during fruit development in satsuma mandarin]. 1562 93

Previously, we reported that mitogenicity in L6 muscle cells was stimulated by insulin but inhibited by reactive oxygen/nitrogen species (ROS/RNS; []) and that preincubation with sodium ascorbate (ASC) protected from either the impaired DNA synthesis and/or loss of cell viability. Now, we addressed the question how ascorbate (AA) rescued DNA synthesis in L6 muscle cells being challenged with ROS/RNS. We assumed that AA might be able to influence insulin signaling. We found that insulin elevated the protein levels of both PKB/Akt kinase phosphorylated at Serine(473) (pS473-Akt), and c-Jun phosphorylated at Serine63, Serine73 (pS63, pS73-c-Jun) residues, respectively. A short-term treatment experiment (0 - 45 min) revealed that either insulin (0.1 muM) or hydrogen peroxide (0.1, 0.5 mM; H2O2) increased the pS473-Akt and pS63, pS73-c-Jun protein levels, although the effect of ROS/RNS peaked earlier (5 min) than that of insulin (45 min). Astonishingly, the elevated levels of both pS473-Akt and pS63, pS73-c-Jun in response to insulin were reduced by the concomitant treatment with H2O2 in a dose-dependent fashion. In contrast, a 4-hour preincubation with ASC (1 mM) augmented the signal from pS473-Akt and pS63, pS73-c-Jun, when both insulin and H2O2 were added. Moreover, a 24 h preincubation with ASC also elevated the pS473-Akt and pS63, pS73-c-Jun levels in response to insulin irrespective to ROS/RNS co-treatment. During chronic treatment studies, ROS/RNS stimulated neither phosphorylation of Akt nor c-Jun, indicating that ROS/RNS-dependent activation of the above-mentioned proteins was short-term and transient. Furthermore, higher levels of pS473 Akt and pS63, pS73-c-Jun after preincubation with ASC suggest that by this route AA could protect insulin-induced mitogenicity. Basal levels of Akt and its target p70(S6K) remained constant regardless of treatment. These results suggest that AA defends the insulin-stimulated mitogenicity hampered by ROS/RNS most likely by the amplification of insulin signal at the level of pS473-Akt and pS63, pS73-c-Jun, respectively.
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PMID:Preincubation with sodium ascorbate potentiates insulin-dependent PKB/Akt and c-Jun phosphorylation in L6 rat myoblasts challenged with reactive oxygen/nitrogen species. 1590 68

A new sorbent was synthesized by anchoring 7-amino-4-azaheptyltrimetoxisilane, freshly prepared, to silica gel, producing 7-amino-4-azaheptyl anchored silica gel (AAHSG). This material was characterized by infrared spectroscopy (IR), elemental analysis (CHN), and nitrogen adsorption-desorption isotherms. Isotherms of the adsorption of Fe3+, Fe2+ and Cu2+ on AAHSG were recorded, which indicated that Fe3+ presents a higher affinity by the sorbent. Therefore, AAHSG was successfully employed as a sorbent in a simple flow system for the preconcentration of Fe3+ in natural water samples, such as, river water, lagoonwater, springwater, stream water, well water and two water reference materials (NIST-SRM 1640, NIST-SRM 1643d). The obtained preconcentration factor was 82.2, and the detection limit achieved was 5.9 ng ml(-1). The recovery of spiked water samples ranged from 95.0 - 103.1%.
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PMID:7-amino-4-azaheptyl grafted onto a silica gel as a sorbent for the on-line preconcentration and determination of iron(III) in water samples. 1591 51

Effects of synchronizing the availability of amino acids and glucose within a day on protein and energy metabolism were studied in heavy preruminant calves. Thirty-six preruminant calves (148 +/- 1.6 kg body weight) were assigned to 1 of 6 degrees of nutrient synchrony (SYN, 1-6) and to 1 of 2 meal sequences (i.e., the high-protein meal in the morning or in the evening). Calves at SYN 1 received 2 balanced meals: one at 0600 and one at 1800. Nutrient synchrony decreased stepwise from SYN 1 to SYN 6 in which calves received 85% of the daily protein supply in 1 meal. The digestible energy intakes at 0600 and 1800 were equal between treatments. Daily intakes of all nutrients and dietary ingredients were identical for all treatments. Calves were housed individually in respiration chambers. Apparent fecal nutrient digestibility and nitrogen and energy balances were measured. Apparent nutrient digestibility decreased when >71% of the dietary protein was fed in one meal. Nutrient synchrony did not affect the efficiency of digestible protein utilization in calves at a identical digestible nutrient intake. Heat production decreased from 691 to 629 kJ/(kg(0.75) x d) (P < 0.05) and energy retained as fat increased from 116 to 184 kJ/(kg(0.75) x d) (P < 0.01) with decreasing nutrient synchrony. Meal sequence did not affect any of the traits. In conclusion, synchronizing the availability of amino acids and glucose within a day did not increase the efficiency of protein utilization but substantially decreased fat retention in heavy preruminant calves.
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PMID:Synchronizing the availability of amino acids and glucose decreases fat retention in heavy preruminant calves. 1685 38

In this work, we investigated the effects of pH and nitrogen forms on iron homeostasis and the expression profiles of genes involved in iron uptake and metabolism using tomato cultivar T3238 and its iron-inefficient mutant T3238fer. We showed that high external pH led to increased expression of four iron uptake genes (LeIRT1, LeIRT2, LeFRO1, LeNRAMP1) regardless of the nitrogen sources. Interestingly, the transcript level of FER was decreased at high pH and increased at low pH. In iron-inefficient mutant T3238fer, the expression of LeFRO1, LeIRT1 and LeNRAMP1 was much less than wild type under the culture conditions with high pH and on the non-buffered agar medium with NO(3) (-) as the sole N source, demonstrating that FER protein is required for the increased expression of LeFRO1, LeIRT1 and LeNRAMP1 under culture conditions with high pH. Considering the paradoxical expression patterns of FER to LeFRO1, LeIRT1 and LeNRAMP1 in T3238, we speculate that FER is essential, but is not the limited factor for the transcriptional regulation of the three iron uptake genes. In conclusion, the alteration of rhizosphere pH by assimilating NO(3) (-) or NH(4) (+) influenced Fe availability and consequently affected iron homeostasis in tomato. The enhanced expression of LeFRO1, LeIRT1 and LeNRAMP1 under the culture condition with high pH or on agar media with NO(3) (-) as the sole N source might be a consequence of reduced iron availability in the solution or agar medium at high pH.
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PMID:Effects of pH and nitrogen forms on expression profiles of genes involved in iron homeostasis in tomato. 1732 37

The Target of Rapamycin (TOR) protein is a Ser/Thr kinase that functions in two distinct multiprotein complexes: TORC1 and TORC2. These conserved complexes regulate many different aspects of cell growth in response to intracellular and extracellular cues. Here we report that the AGC kinase Sch9 is a substrate of yeast TORC1. Six amino acids in the C terminus of Sch9 are directly phosphorylated by TORC1. Phosphorylation of these residues is lost upon rapamycin treatment as well as carbon or nitrogen starvation and transiently reduced following application of osmotic, oxidative, or thermal stress. TORC1-dependent phosphorylation is required for Sch9 activity, and replacement of residues phosphorylated by TORC1 with Asp/Glu renders Sch9 activity TORC1 independent. Sch9 is required for TORC1 to properly regulate ribosome biogenesis, translation initiation, and entry into G0 phase, but not expression of Gln3-dependent genes. Our results suggest that Sch9 functions analogously to the mammalian TORC1 substrate S6K1 rather than the mTORC2 substrate PKB/Akt.
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PMID:Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. 1761 50

In order to discover potential markers of prognosis in colorectal cancer (CRC) we have determined gene expression profiles, using cDNA microarrays in CRC samples obtained from 19 patients in Dukes stages C and D, with favorable clinical course (Dukes C patients, survival >5 years after surgery, group A, n=7) or unfavorable clinical course (Dukes stage C and D patients, survival <5 years after surgery, group B, n=12). Gene expression was measured in RNA from each tumor, using a pool of equal amounts of RNA from all tumors as a reference. To identify and rank differentially expressed genes we used three different analytical methods: (i) Significance Analysis of Microarrays (SAM), (ii) Cox's Proportional Hazard Model, and (iii) Trend Filter (a mathematical method for the assessment of numerical trends). The level of expression of a gene in an individual tumor was regarded as of interest when that gene was identified as differentially expressed by at least two of these three methods. By these stringent criteria we identified eight genes (ITGB2, MRPS11, NPR1, TXNL2, PHF10, PRSS8, KCNK3, JAK3) that were correlated with prolonged survival after surgery. Pathway analysis showed that patients with favorable prognosis had several activated metabolic pathways (carbon metabolism, transcription, amino acid and nitrogen metabolism, signaling and fibroblast growth factor receptor pathways). To further validate individual gene expression findings, the RNA level of each gene identified as a marker with microarrays was measured by real-time RT-PCR in CRC samples from an independent group of 55 patients. In this set of patients the Cox Proportional Hazard Model analysis demonstrated a significant association between increased patient survival and low expression of ITGB2 (p = 0.011) and NPR1 (p = 0.023) genes.
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PMID:Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer. 1830 33


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