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Synthesis Inhibition (synthesis + inhibition)
Kinds of Synthesis Inhibition Selected AbstractsNitric Oxide Synthesis Inhibition Attenuates Conditioned Reinstatement of Ethanol-Seeking, but Not the Primary Reinforcing Effects of EthanolALCOHOLISM, Issue 8 2004Xiu Liu Background: Nitric oxide (NO) signaling has been implicated in regulating aspects of the reinforcing and addictive actions of cocaine. These experiments were designed to examine whether NO-dependent neurotransmission also participates in mediating the addictive actions of another drug of abuse, ethanol, with emphasis on both the primary reinforcing effects of ethanol and the incentive motivational effects of ethanol-related contextual stimuli. Methods: Male Wistar rats were operantly trained to orally self-administer 10% (w/v) ethanol in daily 30-min sessions and to associate distinct discriminative stimuli with the availability of ethanol (S+) versus nonreward (S,). Rats were treated with the NO synthase inhibitor NG -nitro-l-arginine methyl ester (l-NAME; 0, 10, or 40 mg/kg intraperitoneally) 30 min before self-administration tests that were conducted after establishment of stable levels of daily ethanol intake and conditioned reinstatement tests that were performed after extinction of ethanol-maintained operant responding. Results: l-NAME did not alter the primary reinforcing effects of ethanol in self-administration tests. In contrast, l-NAME dose-dependently attenuated the recovery of extinguished responding induced by the ethanol S+ in the absence of ethanol availability during reinstatement tests. Conclusions: These results suggest that the NO system does not play a role in behavior reinforced directly by ethanol. However, the results implicate NO-dependent neurotransmission in alcohol-seeking responses elicited by drug-related contextual stimuli. [source] Histone H1 and MAP Kinase Activities in Bovine Oocytes following Protein Synthesis InhibitionREPRODUCTION IN DOMESTIC ANIMALS, Issue 3-4 2001B Meinecke In vitro nuclear maturation is associated with known activity profiles of the M-phase promoting factor (MPF) and the mitogen-activated protein (MAP) kinases, which are two key regulators of mitotic and meiotic cell cycles. Initiation of meiotic resumption in vitro can be prevented by cycloheximide treatment and after removal of the inhibitor germinal vesicle breakdown takes place nearly twice as fast as in untreated controls. In this study experiments were conducted in order to examine the chromosome condensation status and the dynamics of MPF and MAP kinase activities after cycloheximide treatment (10 ,g/ml) of cumulus-enclosed oocytes for 17 and 24 h, respectively, and subsequent culture in inhibitor-free medium for various times. Bovine oocytes displayed variations in the degree of chromosome condensation at the end of the inhibitor treatment phase. Following removal of the inhibitor germinal vesicle breakdown occurred after 4,5 h of subsequent culture in inhibitor-free medium. MPF and MAP kinase exhibited low activities during the first 1,3 h following cycloheximide treatment. Increasing levels of enzyme activities were detected 4,7 h following cycloheximide treatment for 17 and 24 h, respectively, and subsequent culture in inhibitor-free medium. The patterns of enzyme activities corresponded with the accelerated nuclear maturation process. It can be concluded that cycloheximide treatment does not lead to a more synchronous course of nuclear maturation and that the activities of both, MPF and MAP kinase are initiated at least 2,5 h earlier in comparison with untreated oocytes. [source] Protein synthesis inhibition before or after stress exposure results in divergent endocrine and BDNF responses disassociated from behavioral responsesDEPRESSION AND ANXIETY, Issue 5 2008Nitsan Kozlovsky Ph.D. Abstract This study aimed to assess the effects of anisomycin, a protein synthesis inhibitor, on behavioral responses, brain-derived neurotrophic factor (BDNF) and TrkB mRNA levels, and circulating corticosterone in rats,when administered before or after initial exposure to a predator scent stress stimulus. Magnitude of changes in prevalence of anxiety-like behaviors on the elevated plus-maze and exaggerated startle reaction as well as corticosterone levels and mRNA BDNF and TrkB were compared in rats exposed to predator stress, microinjected with anisomycin before or after stress exposure. Administration of anisomycin before or after stress exposure reduced anxiety-like behavior in the elevated plus-maze and reduced the mean startle amplitude 7 days postexposure. Although the behavioral responses were similar when anisomycin was microinjected before or after stress exposure, the levels of mRNAs for BDNF and TrkB, which play a role in modulation of synaptic plasticity and the consolidation process, showed varying responses. Depression and Anxiety 0:1,11, 2007. © 2007 Wiley-Liss, Inc. [source] Effects of locomotor stimulation and protein synthesis inhibition on circadian rhythms in size changes of L1 and L2 interneurons in the fly's visual systemDEVELOPMENTAL NEUROBIOLOGY, Issue 11 2007Elzbieta Kula Abstract Axons of monopolar cell interneurons L1 and L2 in the first optic lobe (lamina) of the fly Musca domestica undergo cyclical changes in diameter. These axons swell during the day and shrink during the night. In addition, the axons' size depends on light conditions since they are largest in continuous light (LL), somewhat smaller under day/night (LD) conditions, and smallest under constant darkness (DD). In this study we found that sizes of both cells can further increase in free flying flies under LD conditions, while the visual stimulation alone does not have significant effect on the cross-sectional area of L1 and L2 axons. The stimulation of free flying had no effect on L1 and L2 sizes if it was performed at the beginning of subjective day in LL or DD. Our results indicate that a maximal increase in size of L1 and L2 is observed when stimulation of free flying is synchronized with a fly' daily peak of activity. We also found that protein synthesis is needed to increase size of monopolar cell axons during the day when they normally swell. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007. [source] An in vitro study of the interaction of sea-nine® with rat liver mitochondriaENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 5 2005Marcantonio Bragadin Abstract The interactions of the antifouling compound Sea-Nine® with rat liver mitochondria have been studied. The results indicate that low doses of this compound inhibit adenosine 5,-triphosphate (ATP) synthesis. Further investigations indicate that ATP synthesis inhibition should be due to an interaction of Sea-Nine with the succinic dehydrogenase in the mitochondrial respiratory chain. [source] From learning to forgetting: Behavioral, circuitry, and molecular properties define the different functional states of the recognition memory traceHIPPOCAMPUS, Issue 5 2010Rocío Romero-Granados Abstract Neuropsychological analyses of amnesic patients, as well as lesion experiments, indicate that the temporal lobe is essential for the encoding, storage, and expression of object recognition memory (ORM). However, temporal lobe structures directly involved in the consolidation and reconsolidation of these memories are not yet well-defined. We report here that systemic administration of a protein synthesis inhibitor before or up to 4 h after training or reactivation sessions impairs consolidation and reconsolidation of ORM, without affecting short-term memory. We have also observed that ORM reconsolidation is sensitive to protein synthesis inhibition, independently of the ORM trace age. Using bdnf and egr-1 gene expression analysis, we defined temporal lobe areas related to consolidation and reconsolidation of ORM. Training and reactivation 21 days after ORM acquisition sessions provoked changes in bdnf mRNA in somatosensory, perirhinal, and hippocampal cortices. Reactivation 2 days after the training session elicited changes in bdnf and egr-1 mRNA in entorhinal and prefrontal cortices, while reactivation 9 days post-training provoked an increase in egr-1 transcription in somatosensory and entorhinal cortices. The differences in activated circuits and in the capacity to recall the memory trace after 9 or 21 days post-training suggest that memory trace suffers functional changes in this period of time. All these results indicate that the functional state of the recognition memory trace, from acquisition to forgetting, can be specifically defined by behavioral, circuitry, and molecular properties. © 2009 Wiley-Liss, Inc. [source] Butterfat fatty acids differentially regulate growth and differentiation in Jurkat T-cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2005Paolo Bergamo Abstract Synthetic Conjugated Linoleic Acid mixture (CLA; c9,t11; t10,c12-18:2) has been previously shown to inhibit growth, and enhance apoptosis and IL-2 mRNA synthesis in human lymphoblastic Jurkat T-cells. In this study, two different butterfat types were evaluated and compared for their effects on Jurkat cell viability, oxidative stress, pro-apoptotic activity, and cytokine synthesis: the conventionally produced butterfat (CBF), and organic butterfat (OBF) containing significantly higher amounts of c9,t11 (Rumenic Acid, RA), trans-vaccenic acid (VA; t11-18:1), ,-linolenic acid (ALA), and lower levels of linoleic acid (LA). Results from cell treatment with both butterfat mixtures showed comparable oxidative stress (superoxide production, intracellular GSH depletion,and lipid peroxides yield), NADPH oxidase activation, cytotoxicity (LDH release), and IL-2 transcript level, whereas the effects of enhanced growth-inhibitory and pro-apoptotic activities were associated with OBF treatment. To then investigate each butterfat-induced effect caused by RA, VA, LA, and ALA, cells were exposed to synthetic FA concentrations similar to those from the different butterfats. Higher oxidative stress (superoxide production, intracellular GSH depletion) was induced by ,-linolenic (ALA) and linoleic (LA) incubation (P,<,0.01) and superoxide production was suppressed by specific PKC, inhibitor (Gö 6976) and linked to increased toxicity and IL-2 synthesis inhibition. By contrast, cell treatment with RA increased apoptosis and IL-2 synthesis. These results suggest that a supply of ALA and LA is responsible for BF-induced oxidative stress via PKC,-NADPH oxidase pathway, and that enhanced antiproliferative effects in OBF treated cells is essentially determined by RA-induced pro-apoptotic activity. © 2005 Wiley-Liss, Inc. [source] Nitric oxide synthesis inhibition alters rat cutaneous wound healingJOURNAL OF CUTANEOUS PATHOLOGY, Issue 7 2006Thaís P. Amadeu Background:, Nitric oxide (NO) is an important molecule that participates in wound repair, but its effects on cutaneous wound healing are not well understood. The aim of this study was to investigate the effects of NO synthesis blockade on rat cutaneous wound healing by the administration of NG -nitro- l -arginine methyl ester (l -NAME), a non-selective inhibitor of NO synthases. Methods:, NO synthesis was inhibited by administration of l -NAME (20 mg/kg/day) in drinking water. An excisional wound was done, and the animals were killed 7, 14, and 21 days later. Wound contraction and blood pressure were evaluated. The lesion and adjacent skin were formalin fixed and paraffin embedded. Mast cells were quantified, and vessels were evaluated using stereological methods. Results:,l -NAME-treated animals presented delayed wound contraction, alterations in collagen organization, and neoepidermis thickness. The inhibition of NO synthesis increased mast cell migration 7 days after wounding, but decreased 21 days after wounding. Volume density of vessels was decreased in l -NAME-treated animals, 21 days after lesion. Surface density of vessels was frequently smaller in l -NAME-treated animals than in controls. Conclusion:, The blockade of NO synthesis impaired cutaneous wound healing, acting in early and late phases of wound repair. [source] 2-Deoxyglucose and NMDA inhibit protein synthesis in neurons and regulate phosphorylation of elongation factor-2 by distinct mechanismsJOURNAL OF NEUROCHEMISTRY, Issue 3 2006M. Maus Abstract Cerebral ischaemia is associated with brain damage and inhibition of neuronal protein synthesis. A deficit in neuronal metabolism and altered excitatory amino acid release may both contribute to those phenomena. In the present study, we demonstrate that both NMDA and metabolic impairment by 2-deoxyglucose or inhibitors of mitochondrial respiration inhibit protein synthesis in cortical neurons through the phosphorylation of eukaryotic elongation factor (eEF-2), without any change in phosphorylation of initiation factor eIF-2,. eEF-2 kinase may be activated both by Ca2+ -independent AMP kinase or by an increase in cytosolic Ca2+. Although NMDA decreases ATP levels in neurons, only the effects of 2-deoxyglucose on protein synthesis and phosphorylation of elongation factor eEF-2 were reversed by Na+ pyruvate. Protein synthesis inhibition by 2-deoxyglucose was not as a result of a secondary release of glutamate from cortical neurons as it was not prevented by the NMDA receptor antagonist 5-methyl-10,11-dihydro-5H-dibenzo-(a,d)-cyclohepten-5,10-imine hydrogen maleate (MK 801), nor to an increase in cytosolic-free Ca2+. Conversely, 2-deoxyglucose likely activates eEF-2 kinase through a process involving phosphorylation by AMP kinase. In conclusion, we provide evidence that protein synthesis can be inhibited by NMDA and metabolic deprivation by two distinct mechanisms involving, respectively, Ca2+ -dependent and Ca2+ -independent eEF-2 phosphorylation. [source] Difluoromethylornithine Decreases Long-Lasting Protein Oxidation Induced by Neonatal Ethanol Exposure in the Hippocampus of Adolescent RatsALCOHOLISM, Issue 5 2007Carlos Fernando Mello Background: Ethanol exposure and withdrawal during central nervous system development can cause oxidative stress and produce severe and long-lasting behavioral and morphological alterations in which polyamines seem to play an important role. However, it is not known if early ethanol exposure causes long-lasting protein oxidative damage and if polyamines play a role in such a deleterious effect of ethanol. Methods: In this study we investigated the effects of early ethanol exposure (6 g/kg/d, by gavage), from postnatal day (PND) 1 to 8, and of the administration of difluoromethylornithine (DFMO, 500 mg/kg, i.p., on PND 8), a polyamine biosynthesis inhibitor, on the extent of oxidative modification of proteins. Indices of oxidative modification of proteins included protein carbonyls, 3-nitrotyrosine (3-NT), and protein bound 4-hydroxynonenal (HNE) in the hippocampus, cerebellum, hypothalamus, striatum, and cerebral cortex of Sprague,Dawley rats at PND 40. Results: Both ethanol and DFMO administration alone increased protein carbonyl immunoreactivity in the hippocampus at PND 40, but the combination of DFMO and ethanol resulted in no effect on protein carbonyl levels. No alterations in the content of protein-bound HNE, 3-NT, or carbonyl were found in any other cerebral structure. Conclusions: These results suggest that the hippocampus is selectively affected by early ethanol exposure and by polyamine synthesis inhibition. In addition, the results suggest a role for polyamines in the long-lasting increase of protein carbonyls induced by ethanol exposure and withdrawal. [source] Acyl carrier protein/SpoT interaction, the switch linking SpoT-dependent stress response to fatty acid metabolismMOLECULAR MICROBIOLOGY, Issue 4 2006Aurélia Battesti Summary Bacteria respond to nutritional stresses by producing an intracellular alarmone, guanosine 5,-(tri)diphosphate, 3,-diphosphate [(p)ppGpp], which triggers the stringent response resulting in growth arrest and expression of resistance genes. In Escherichia coli, upon fatty acid or carbon starvation, SpoT enzyme activity switches from (p)ppGpp degradation to (p)ppGpp synthesis, but the signal and mechanism for this response remain totally unknown. Here, we characterize for the first time a physical interaction between SpoT and acyl carrier protein (ACP) using affinity co-purifications and two-hybrid in E. coli. ACP, as a central cofactor in fatty acid synthesis, may be an ideal candidate as a mediator signalling starvation to SpoT. Accordingly, we show that the ACP/SpoT interaction is specific of SpoT and ACP functions because ACP does not interact with the homologous RelA protein and because SpoT does not interact with a non-functional ACP. Using truncated SpoT fusion proteins, we demonstrate further that ACP binds the central TGS domain of SpoT, consistent with a role in regulation. The behaviours of SpoT point mutants that do not interact with ACP reveal modifications of the balance between the two opposite SpoT catalytic activities thereby changing (p)ppGpp levels. More importantly, these mutants fail to trigger (p)ppGpp accumulation in response to fatty acid synthesis inhibition, supporting the hypothesis that the ACP/SpoT interaction may be involved in SpoT-dependent stress response. This leads us to propose a model in which ACP carries information describing the status of cellular fatty acid metabolism, which in turn can trigger the conformational switch in SpoT leading to (p)ppGpp accumulation. [source] The Role of Cytokines in Regulating Protein Metabolism and Muscle FunctionNUTRITION REVIEWS, Issue 2 2002Elena Zoico M.D. Multiple lines of evidence suggest that cytokines influence different physiologic functions of skeletal muscle cells, including anabolic and catabolic processes and programmed cell death. Cytokines play an important role not only in muscle homeostasis, therefore, but also in the pathogenesis of different relevant clinical conditions characterized by alterations in protein metabolism. Recently discovered cytokines, such as ciliary neurotrophic factor and growth/differentiation factor-8, as well as the more studied tumor necrosis factor-,, interleukin-1, interleukin-6, and the interferons, have been implicated in the regulation of muscle protein turnover. Their postreceptor signaling pathways, proteolytic systems, and the mechanisms of protein synthesis inhibition involved in different catabolic conditions have been partially clarified. Moreover, recent studies have shown that cytokines can directly influence skeletal muscle contractility independent of changes in muscle protein content. Even though several gaps remain in our understanding, these observations may be useful in the development of strategies to control protein metabolism and muscle function in different clinical conditions. [source] | |||||||||||||