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51.
52.
Charles A. Berdan Karel A. Erion Nathan E. Burritt Barbara E. Corkey Jude T. Deeney 《PloS one》2016,11(2)
Lipid signals derived from lipolysis and membrane phospholipids play an important role in glucose-stimulated insulin secretion (GSIS), though the exact secondary signals remain unclear. Previous reports have documented a stimulatory role of exogenously added mono-acyl-glycerol (MAG) on insulin secretion from cultured β-cells and islets. In this report we have determined effects of increasing intracellular MAG in the β-cell by inhibiting mono-acyl-glycerol lipase (MGL) activity, which catalyzes the final step in triacylglycerol breakdown, namely the hydrolysis of MAG to glycerol and free fatty acid (FA). To determine the role of MGL in GSIS, we used three different pharmacological agents (JZL184, MJN110 and URB602). All three inhibited GSIS and depolarization-induced insulin secretion in INS-1 (832/13). JZL184 significantly inhibited both GSIS and depolarization-induced insulin secretion in rat islets. JZL184 significantly decreased lipolysis and increased both mono- and diacyglycerol species in INS-1 cells. Analysis of the kinetics of GSIS showed that inhibition was greater during the sustained phase of secretion. A similar pattern was observed in the response of Ca2+ to glucose and depolarization but to a lesser degree suggesting that altered Ca2+ handling alone could not explain the reduction in insulin secretion. In addition, a significant reduction in long chain-CoA (LC-CoA) was observed in INS-1 cells at both basal and stimulatory glucose following inhibition of MGL. Our data implicate an important role for MGL in insulin secretion. 相似文献
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54.
Maud N. Vissers Peter L. Zock Rianne Leenen Annet J.C. Roodenburg Karel P.A.M. Van Putte Martijn B. Katan 《Free radical research》2013,47(5):619-629
A high intake of olive oil has been proposed as an explanation for the low incidence of coronary heart disease in Mediterranean countries, but it is unclear whether olive oil offers specific benefits beyond a low content of saturated fat. Some types of extra virgin olive oil are rich in non-polar phenols, which might be taken up by plasma LDL particles and protect these from becoming atherogenic by oxidative modification. In a pilot study we found that consumption of 47 g fortified olive oil containing 31 mg phenols significantly increased the lag time of LDL oxidation from 112 ± 5 min before to 130 ± 7 min 2h after the meal. However, this study was not controlled, and in the current study we therefore investigated whether olive oil phenols increase the lag time of LDL oxidation in postprandial samples when compared with a control group.Twelve healthy men and women consumed four different olive oil supplements with a meal on four separate occasions: one similar to the supplement in the pilot study (positive control); one containing mainly non-polar olive oil phenols; one containing mainly polar olive oil phenols; and one without phenols (placebo). Lag time significantly increased 2 h after the meals with the positive control (8 ± 2 min), the polar phenols (8 ± 2 min), and the placebo (8 ± 2 min), but not after the non-polar phenols (-0.4 ± 3 min). Increases were not statistically different between supplements.These results indicate that the lag time of LDL-oxidation is increased after consumption of a meal. This increase is probably due to non-specific meal or time effects and not to phenols from olives or olive oil. Furthermore, these findings stress the need for adequate controlled studies to avoid misinterpretations of the data. 相似文献
55.
Mohamed I. Elzagheid Mikko Oivanen Karel D. Klika Bryan C. N. M. Jones Richard Cosstick Harri Lönnberg 《Nucleosides, nucleotides & nucleic acids》2013,32(9):2093-2108
Abstract The course of hydrolysis of 3′-deoxy-3′-thioinosylyl-(3′ → 5′)-uridine (IspU) has been followed by HPLC over a wide pH-range. Two reactions of the internucleosidic thiophosphate linkage compete: (i) cleavage yielding thioinosine monophosphates and uridine, and (ii) isomerization to the 2′,5′-isomer of IspU. Under very acidic conditions, even acid-catalyzed depurination of the inosine moiety is observed. The stability of the thiophosphate linkage and the mechanisms of its rupture are discussed. 相似文献
56.
Karel Pomeisl Květoslava Horská Radek Pohl Jiří Blažek Marcela Krečmerová 《Nucleosides, nucleotides & nucleic acids》2013,32(3):159-171
A series of new monophosphates of 1-[2-(phosphonomethoxy)alkyl]thymines, such as PMPTp, 3-MeO-PMPTp, HPMPTp, and FPMPTp, were synthesized and tested for their ability to inhibit human thymidine phosphorylase. Kinetic measurements of enzyme activity were performed using thymidine and inorganic phosphate as the substrates. The data show that some monophosphates provide a considerable increase of the multisubstrate inhibitory effect. The highest inhibitory potency was found with (R)-FPMPTp 4c (K i dT = 4.09 ± 0.47 μM, K i(Pi) = 2.13 ± 0.29 μM) and (R) 3-MeO-PMPTp 4d (K i dT = 5.78 ± 0.71 μM, K i(Pi) = 2.71 ± 0.37 μM). 相似文献
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58.
Carlos Oscar Sánchez Sorzano Alberto Pascual-Montano Ainhoa Sánchez de Diego Carlos Martínez-A Karel H.M. van Wely 《Cell cycle (Georgetown, Tex.)》2013,12(13):2016-2023
The acquisition of massive but localized chromosome translocations, a phenomenon termed chromothripsis, has received widespread attention since its discovery over a year ago. Until recently, chromothripsis was believed to originate from a single catastrophic event, but the molecular mechanisms leading to this event are yet to be uncovered. Because a thorough interpretation of the data are missing, the phenomenon itself has wrongly acquired the status of a mechanism used to justify many kinds of complex rearrangements. Although the assumption that all translocations in chromothripsis originate from a single event has met with criticism, satisfactory explanations for the intense but localized nature of this phenomenon are still missing. Here, we show why the data used to describe massive catastrophic rearrangements are incompatible with a model comprising a single event only and propose a molecular mechanism in which a combination of known cellular pathways accounts for chromothripsis. Instead of a single traumatic event, the protection of undamaged chromosomes by telomeres can limit repetitive breakage-fusion-bridge events to a single chromosome arm. Ultimately, common properties of chromosomal instability, such as aneuploidy and centromere fission, might establish the complex genetic pattern observed in this genomic state. 相似文献
59.
Yuri M. Moshkin Cecile M. Doyen Tsung-Wai Kan Gillian E. Chalkley Karen Sap Karel Bezstarosti Jeroen A. Demmers Zeliha Ozgur Wilfred F. J. van Ijcken C. Peter Verrijzer 《PLoS genetics》2013,9(9)
Chromosome duplication and transmission into daughter cells requires the precisely orchestrated binding and release of cohesin. We found that the Drosophila histone chaperone NAP1 is required for cohesin release and sister chromatid resolution during mitosis. Genome-wide surveys revealed that NAP1 and cohesin co-localize at multiple genomic loci. Proteomic and biochemical analysis established that NAP1 associates with the full cohesin complex, but it also forms a separate complex with the cohesin subunit stromalin (SA). NAP1 binding to cohesin is cell-cycle regulated and increases during G2/M phase. This causes the dissociation of protein phosphatase 2A (PP2A) from cohesin, increased phosphorylation of SA and cohesin removal in early mitosis. PP2A depletion led to a loss of centromeric cohesion. The distinct mitotic phenotypes caused by the loss of either PP2A or NAP1, were both rescued by their concomitant depletion. We conclude that the balanced antagonism between NAP1 and PP2A controls cohesin dissociation during mitosis. 相似文献
60.
Pablo García-Gómez Abdellatif Bahaji Samuel Gámez-Arcas Francisco José Muñoz Ángela María Sánchez-López Goizeder Almagro Edurne Baroja-Fernández Kinia Ameztoy Nuria De Diego Lydia Ugena Lukáš Spíchal Karel Doležal Mohammad-Reza Hajirezaei Luis C. Romero Irene García Javier Pozueta-Romero 《Plant, cell & environment》2020,43(10):2551-2570