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    Wyświetlanie 1-4 z 4
    Tytuł:
    [5-(Benzyloxy)-1H-indol-1-yl]acetic acid, an aldose reductase inhibitor and PPARγ ligand
    Autorzy:
    Soltesova Prnova, Marta
    Majekova, Magdalena
    Milackova, Ivana
    Díez-Dacal, Beatriz
    Pérez-Sala, Dolores
    Ceyhan, Muserref
    Banerjee, Sreeparna
    Stefek, Milan
    Powiązania:
    https://bibliotekanauki.pl/articles/1038997.pdf
    Data publikacji:
    2015
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    aldose reductase inhibitor
    PPARγ ligand
    diabetes
    indole
    Opis:
    Based on overlapping structural requirements for both efficient aldose reductase inhibitors and PPAR ligands, [5-(benzyloxy)-1H-indol-1-yl]acetic acid (compound 1) was assessed for inhibition of aldose reductase and ability to interfere with PPARγ. Aldose reductase inhibition by 1 was characterized by IC50 in submicromolar and low micromolar range, for rat and human enzyme, respectively. Selectivity in relation to the closely related rat kidney aldehyde reductase was characterized by approx. factor 50. At organ level in isolated rat lenses, compound 1 significantly inhibited accumulation of sorbitol in a concentration-dependent manner. To identify crucial interactions within the enzyme binding site, molecular docking simulations were performed. Based on luciferase reporter assays, compound 1 was found to act as a ligand for PPARγ, yet with rather low activity. On balance, compound 1 is suggested as a promising lead-like scaffold for agents with the potential to interfere with multiple targets in diabetes.
    Źródło:
    Acta Biochimica Polonica; 2015, 62, 3; 523-528
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Conjugated linoleic acids regulate triacylglycerol and cholesterol concentrations in macrophages/foam cells by the modulation of CD36 expression
    Autorzy:
    Stachowska, Ewa
    Baskiewicz, Magdalena
    Marchlewicz, Mariola
    Czupryńska, Katarzyna
    Kaczmarczyk, Mariusz
    Wiszniewska, Barbara
    Machaliński, Bogusław
    Chlubek, Dariusz
    Powiązania:
    https://bibliotekanauki.pl/articles/1040388.pdf
    Data publikacji:
    2010
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    CD36
    triacylglycerols
    foam cells
    cholesterol
    PPAR
    CLA
    macrophages
    Opis:
    Atherosclerosis is an inflammatory disease characterised by the accumulation of lipids and their metabolites in the artery wall. During inflammation circulating LDL are taken up by macrophages through two major scavenger receptors: CD36 and scavenger receptor A (SRA). Fatty acids that are common in food, e.g. linoleic acid and n-3 unsaturated fatty acids can modulate expression of CD36 on the macrophage surface. Conjugated linoleic acid isomers (CLA) that originate from the human diet, have demonstrated antiatherogenic properties in several experiments. Animal study evidenced that CLA could induce resolution of plaque by activation of peroxisome proliferator activated receptors and down-regulation of pro-inflammatory genes. Less unequivocal results were obtained in human studies (on the CLA effects on the inflammatory process). Therefore in this study we investigated the influence of CLA on CD36 expression and lipid accumulation in human macrophages. Macrophages were incubated with 30 µM cis-9,trans-11 CLA, trans-10,cis-12 CLA or linoleic acid for 48 h. After that, expression of CD36 as well as accumulation of lipids were measured by flow cytometry, microscopy and a spectroscopic method. We demonstrate that both cis-9,trans-11 C 18:2 CLA and linoleic acid slightly elevated expression of CD36, whereas second isomer - trans-10,cis-12 CLA - did not. Nevertheless, only trans-10,cis-12 CLA triggered delipidation of macrophages, that is decreased triacylglycerols concentration. Also in human adipocytes, trans-10,cis-12 CLA causes cell delipidation by reduction of PPAR receptor expression. We propose a similar mechanism for human macrophages/foam cells.
    Źródło:
    Acta Biochimica Polonica; 2010, 57, 3; 379-384
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Female headstart in resistance to hyperoxia-induced oxidative stress in mice
    Autorzy:
    Šarić, Ana
    Sobočanec, Sandra
    Šafranko, Željka
    Popović-Hadžija, Marijana
    Aralica, Gorana
    Korolija, Marina
    Kušić, Borka
    Balog, Tihomir
    Powiązania:
    https://bibliotekanauki.pl/articles/1039219.pdf
    Data publikacji:
    2014
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    hyperoxia
    sex-related
    mice
    ROS
    Sirt1
    PPAR-γ
    eNOS
    Sod2
    Opis:
    Increased oxygen concentration (hyperoxia) induces oxidative damage of tissues and organs. Oxygen toxicity in hyperoxia is controlled by factors such as sex, age, tissue, strain and hormones. In most species females show lower incidence of some age-related pathologies linked with oxidative stress, which has been attributed to a beneficial effect of ovarian hormones. In this study we found that hyperoxia induced hepatic oxidative damage exclusively in male CBA/H mice, followed by their decreased survival. Histopathological examination revealed that the observed differences in survival were not the consequence of acute lung injury induced by hyperoxia. Next, we observed that an increased Sirt1 protein level in hyperoxia-exposed female CBA/H mice correlated with their lower PPAR-γ and higher eNOS and Sod2 protein levels. In males, higher PPAR-γ and lower Sod2 protein levels were associated with unchanged Sirt1 expression. Although these results are of a correlative nature only, they clearly show that females show better survival, increased resistance to hyperoxia and have generally more efficient defense systems, which suggests that their headstart in resistance to hyperoxia could be a consequence of the beneficial effect of ovarian hormones.
    Źródło:
    Acta Biochimica Polonica; 2014, 61, 4; 801-807
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
    Tytuł:
    Evidence for differential effects of glucose and cycloheximide on mRNA levels of peroxisome proliferator-activated receptor- (PPAR-) machinery members: Superinduction of PPAR-γ1 and -γ2 mRNAs
    Autorzy:
    Rypka, Miroslav
    Veselý, Jaroslav
    Powiązania:
    https://bibliotekanauki.pl/articles/1040405.pdf
    Data publikacji:
    2010
    Wydawca:
    Polskie Towarzystwo Biochemiczne
    Tematy:
    peroxisome proliferator-activated receptor
    HepG2 cells
    mRNA stability
    PPAR-γ coactivator
    superinduction
    Opis:
    Quantitative real-time RT-PCR study was conducted to reveal the effects of normal (5 mmol/l) and high (30 mmol/l) glucose without or with oleate (0.3 mmol/l) on mRNA levels of peroxisome proliferator-activated receptor- (PPAR-)α, -γ1, -γ2, and peroxisome proliferator-activated receptor-γ coactivator- (PGC-)1α and -1β in commercial human hepatoma-derived HepG2 cells maintained under low-serum condition. Significant decrease in PPAR-γ1 and PGC-1α mRNA levels to about 50 % was observed during the first 4 h incubation period. During the next 4 h period, both PPAR-γ1 and PGC-1α mRNAs were partly but significantly restored in high glucose batches. In this period, the presence of the transcriptional inhibitor actinomycin D revealed a significant protective effect of excess glucose on mature PPAR-γ1 and PGC-1α mRNAs. Furthermore, PPAR-γ1 and -γ2 mRNAs were differentially superinduced 1.2-2.5 fold in cells upon the administration of the translational inhibitor cycloheximide. When the cells were co-treated with the combination of cycloheximide and actinomycin D, superinduction was completely suppressed, however. Altogether, the experiments revealed, first, an unexpected protective effect of abundant glucose on PPAR-γ1 and PGC-1α mRNAs in HepG2 cells. Second, we demonstrated cycloheximide-induced, transcription-dependent upregulation of mature PPAR-γ1 and -γ2 mRNAs in HepG2 cells associated with preferential expression of the PPAR-γ2 mRNA variant. The results draw attention to as yet unexplored mechanisms involved in the control of PPAR and PGC genes.
    Źródło:
    Acta Biochimica Polonica; 2010, 57, 2; 209-215
    0001-527X
    Pojawia się w:
    Acta Biochimica Polonica
    Dostawca treści:
    Biblioteka Nauki
    Artykuł
      Wyświetlanie 1-4 z 4

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