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Promoting Properties (promoting + property)
Selected AbstractsThe expression of tubulin polymerization promoting protein TPPP/p25, is developmentally regulated in cultured rat brain oligodendrocytes and affected by proteolytic stressGLIA, Issue 16 2008Olaf Goldbaum Abstract The tubulin polymerization-promoting protein (TPPP)/p25, was identified as a brain specific protein, is associated with microtubules (MTs) in vitro and can promote abnormal MT assembly. Furthermore it has aggregation promoting properties and is a constituent in pathological protein deposits of neurodegenerative diseases. In the brain, TPPP/p25, is present in myelinating oligodendrocytes. Here we show, using cultured rat brain oligodendrocytes, that TPPP/p25, expression is increasing during development in culture, and particularly in immature cells is associated with the centrosome. MT binding properties in oligodendrocytes are rather low, however, when MTs are disassembled by nocodazole, TPPP/p25, accumulates in the perinuclear region. Treatment of oligodendrocytes with the proteasomal inhibitor MG-132 (1 ,M; 18 h) caused an increase in the amount of TPPP/p25, by about 40%, a decrease in its solubility, and led to the appearance of TPPP/p25,-positive cytoplasmic inclusions, which stained with thioflavin S and resembled inclusion bodies. Hence, it might be speculated that acute or chronic malfunction of the proteasomal degradation system, leading to the accumulation of aggregation prone proteins and the pro-aggregatory protein TPPP/p25, or to the aggregation of TPPP/p25, on its own, is causally related to the protein aggregation process in a variety of neurodegenerative diseases. © 2008 Wiley-Liss, Inc. [source] Approaches to measuring the effects of wake-promoting drugs: a focus on cognitive functionHUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue 5 2009Christopher J. Edgar Abstract Objectives In clinical drug development, wakefulness and wake-promotion may be assessed by a large number of scales and questionnaires. Objective assessment of wakefulness is most commonly made using sleep latency/maintenance of wakefulness tests, polysomnography and/or behavioral measures. The purpose of the present review is to highlight the degree of overlap in the assessment of wakefulness and cognition, with consideration of assessment techniques and the underlying neurobiology of both concepts. Design Reviews of four key areas were conducted: commonly used techniques in the assessment of wakefulness; neurobiology of sleep/wake and cognition; targets of wake promoting and/or cognition enhancing drugs; and ongoing clinical trials investigating wake promoting effects. Results There is clear overlap between the assessment of wakefulness and cognition. There are common techniques which may be used to assess both concepts; aspects of the neurobiology of both concepts may be closely related; and wake-promoting drugs may have nootropic properties (and vice versa). Clinical trials of wake-promoting drugs often, though not routinely, assess aspects of cognition. Conclusions Routine and broad assessment of cognition in the development of wake-promoting drugs may reveal important nootropic effects, which are not secondary to alertness/wakefulness, whilst existing cognitive enhancers may have underexplored or unknown wake promoting properties. Copyright © 2009 John Wiley & Sons, Ltd. [source] Purification of citrus limonoids and their differential inhibitory effects on human cytochrome P450 enzymesJOURNAL OF THE SCIENCE OF FOOD AND AGRICULTURE, Issue 9 2007Shibu M Poulose Abstract Recent studies demonstrated that citrus limonoids and flavonoids possess numerous health promoting properties. In the present study, glucosides of limonoids and flavonoids were purified from citrus molasses and limonoid aglycones from citrus seeds. Glucosides were separated on styrene (divinylbenzene), Q-sepharose resins with increasing concentration of sodium chloride. A pH-dependent cold precipitation was carried out for the isolation of naringin in large quantity. Major aglycones such as limonin and nomilin were isolated from seeds by direct crystallization and minor limonoids were purified by vacuum liquid chromatography. The structures of the isolated compounds were confirmed by NMR spectra. Individual limonoids were tested for O -dealkylase and hydroxylase activities of human cytochrome P450 (CYP) isoenzymes such as CYP1A2, CYP1B1, CYP3A4 and CYP19, using ethoxyresorufin, methoxyresorufin and dibenzylfluorescein as substrates. Partial to high inhibition of CYPs was observed in dose-dependent assays. Significant (P < 0.001) reductions in enzyme activities were observed with purified compounds above 2 µmol. Kinetic analyses indicated that limonin glucoside inhibited CYP19 competitively (IC50, 7.1 µ mol L,1), whereas Nomilinic acid glucoside inhibited it noncompetitively (IC50, 9.4 µ mol,1). Nomilinic acid glucoside was the most potent limonoid, with an overall IC50 of < 10 µ mol, for all the enzymes tested. The differential inhibition of CYPs can be ascribed to structural variations of the limonoid nucleus. Limonoid inhibition of key CYPs involved in carcinogenesis supports growing evidence that citrus limonoids act as anticancer agents. Copyright © 2007 Society of Chemical Industry [source] Epigenetic reprogramming of liver cells in tamoxifen-induced rat hepatocarcinogenesisMOLECULAR CARCINOGENESIS, Issue 3 2007Volodymyr P. Tryndyak Abstract Tamoxifen, a nonsteroidal anti-estrogen, is a potent genotoxic hepatocarcinogen in rats, with both tumor initiating and promoting properties. Recently it has been demonstrated that genotoxic carcinogens, in addition to exerting genotoxic effects, often cause epigenetic alterations and these induced epigenetic changes may play important mechanistic role in carcinogenesis. In the present study, we investigated the role of tamoxifen-induced epigenetic changes in hepatocarcinogenic process. The results of the study showed that exposure of female F344 rats to tamoxifen resulted in progressive loss of CpG methylation in regulatory sequences of long interspersed nucleotide elements (LINE-1) and prominent increase in expression of LINE-1 elements and c- myc proto-oncogene. The accumulation of tamoxifen-induced DNA lesions was accompanied by the decreased level of Rad51, Ku70, and DNA polymerase , (Pol,) proteins that play a crucial role in maintenance of genomic stability. Furthermore, feeding rats with tamoxifen-containing diet led to increased regenerative cell proliferation, as indicated by the increased level of Ki-67 and proliferating cell nuclear antigen (PCNA) proteins. These data indicate that exposure of animals to genotoxic hepatocarcinogen tamoxifen led to early phenotypical alterations in livers characterized by emergence of epigenetically reprogrammed cells with a specific cancer-related epigenetic phenotype prior to tumor formation. © 2006 Wiley-Liss, Inc. [source] Molecular targets of [6]-gingerol: Its potential roles in cancer chemopreventionBIOFACTORS, Issue 3 2010Ademola A. Oyagbemi Abstract A wide variety of phenolic compounds derived from spices possess potent antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic activities. [6]-gingerol (1-[4,-hydroxy-3,-methoxyphenyl]-5-hydroxy-3-decanone) is the major pungent principle of ginger, with numerous pharmacological properties including antioxidant, anti-inflammation, and antitumor promoting properties. It could decrease inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-,) expression through suppression of I-kappaB alpha (I,B,) phosphorylation, nuclear factor kappa B (NF-,B) nuclear translocation. Other antiproliferative mechanisms of [6]-gingerol include the release of Cytochrome c, Caspases activation, and increase in apoptotic protease-activating factor-1 (Apaf-1) as mechanism of apoptosis induction. Taken together, the chemopreventive potentials of [6]-gingerol present a promising future alternative to therapeutic agents that are expensive, toxic, and might even be carcinogenic. [source] | |||||||||||||