scholarly journals The influence of D. melanogaster mutations of the kynurenine pathway of tryptophan metabolism on locomotor behavior and expression of genes belonging to glutamatergic and cholinergic systems

2011 ◽  
Vol 9 (2) ◽  
pp. 65-73
Author(s):  
Gennady A Zakharov ◽  
Alexander V Zhuravlev ◽  
Tatyana L Payalina ◽  
Nikolay G Kamyshev ◽  
Elena V Savvateeva-Popova
Keyword(s):  
Kynurenic Acid ◽  
Kynurenine Pathway ◽  
Locomotor Behavior ◽  
Tryptophan Metabolism ◽  
General Level ◽  
Sharp Reduction ◽  
Expression Of Genes ◽  
Age Related ◽  
Signal Cascades ◽  
Age Related Changes

Disbalance of kynurenines produced by Drosophila mutations of the kynurenine pathway of tryptophan metabolism influences the locomotor behavior in larvae. The most pronounced is the effect of accumulation of kynurenic acid in the mutant cinnabar manifested as sharp reduction of general level of locomotor activity. The mutations seem to act through modulatory influences of kynurenines on signal cascades governed by ionotropic glutamatergic and cholinergic receptors. Expression of receptor genes in the mutants shows age-related changes pointing to gradual evolvement of consequences of kynurenines disbalance.

scholarly journals Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression

Genetika ◽  
2014 ◽  
Vol 46 (1) ◽  
pp. 287-301 ◽  
Author(s):  
Biljana Bufan ◽  
Jasmina Djikic ◽  
Mirjana Nacka-Aleksic ◽  
Zorica Stojic-Vukanic ◽  
Mirjana Dimitrijevic ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Rt Pcr ◽  
Autoimmune Encephalomyelitis ◽  
Expression Of Genes ◽  
Age Related ◽  
Genes Encoding ◽  
Immunosuppressive Cytokines ◽  
Age Related Changes ◽  
Experimental Autoimmune

Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund?s adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-? and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+:CD4DC ratio towards CD4-cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+:CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-? mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1? (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1? compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.

scholarly journals Effects of Sleep Deprivation on the Tryptophan Metabolism

2020 ◽  
Vol 13 ◽  
pp. 117864692097090
Author(s):  
Abid Bhat ◽  
Ananda Staats Pires ◽  
Vanessa Tan ◽  
Saravana Babu Chidambaram ◽  
Gilles J Guillemin
Keyword(s):  
Sleep Deprivation ◽  
Kynurenic Acid ◽  
Second Messengers ◽  
Sleep Time ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Cellular Functions ◽  
Intracellular Second Messengers ◽  
The Impact ◽  
The Brain

Sleep has a regulatory role in maintaining metabolic homeostasis and cellular functions. Inadequate sleep time and sleep disorders have become more prevalent in the modern lifestyle. Fragmentation of sleep pattern alters critical intracellular second messengers and neurotransmitters which have key functions in brain development and behavioral functions. Tryptophan metabolism has also been found to get altered in SD and it is linked to various neurodegenerative diseases. The kynurenine pathway is a major regulator of the immune response. Adequate sleep alleviates neuroinflammation and facilitates the cellular clearance of metabolic toxins produced within the brain, while sleep deprivation activates the enzymatic degradation of tryptophan via the kynurenine pathway, which results in an increased accumulation of neurotoxic metabolites. SD causes increased production and accumulation of kynurenic acid in various regions of the brain. Higher levels of kynurenic acid have been found to trigger apoptosis, leads to cognitive decline, and inhibit neurogenesis. This review aims to link the impact of sleep deprivation on tryptophan metabolism and associated complication in the brain.

scholarly journals Multifaceted deregulation of gene expression and protein synthesis with age

2020 ◽  
Vol 117 (27) ◽  
pp. 15581-15590 ◽  
Author(s):  
Aleksandra S. Anisimova ◽  
Mark B. Meerson ◽  
Maxim V. Gerashchenko ◽  
Ivan V. Kulakovskiy ◽  
Sergey E. Dmitriev ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Cell Function ◽  
Altered Expression ◽  
Biomarkers Of Aging ◽  
Expression Of Genes ◽  
Age Related ◽  
Mouse Tissues ◽  
Terminal Oligopyrimidine ◽  
Age Related Changes

Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire life span. We showed that the transcriptome changes govern those in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix, and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5′-terminal oligopyrimidine (5′-TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped twofold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multidimensional deregulation of protein synthesis, showing how this major cellular process declines with age.

scholarly journals Multi-faceted deregulation of gene expression and protein synthesis with age

2020 ◽  
Author(s):  
Aleksandra S. Anisimova ◽  
Mark B. Meerson ◽  
Maxim V. Gerashchenko ◽  
Ivan V. Kulakovskiy ◽  
Sergey E. Dmitriev ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Ribosome Biogenesis ◽  
Cell Function ◽  
Altered Expression ◽  
Biomarkers Of Aging ◽  
Expression Of Genes ◽  
Age Related ◽  
Mouse Tissues ◽  
Terminal Oligopyrimidine ◽  
Age Related Changes

Protein synthesis represents a major metabolic activity of the cell. However, how it is affected by aging and how this in turn impacts cell function remains largely unexplored. To address this question, herein we characterized age-related changes in both the transcriptome and translatome of mouse tissues over the entire lifespan. Expression of the majority of differentially expressed genes followed a U-shaped curve with the turning point around 3-months-old. We showed that transcriptome changes govern changes in the translatome and are associated with altered expression of genes involved in inflammation, extracellular matrix and lipid metabolism. We also identified genes that may serve as candidate biomarkers of aging. At the translational level, we uncovered sustained down-regulation of a set of 5’ terminal oligopyrimidine (5’TOP) transcripts encoding protein synthesis and ribosome biogenesis machinery and regulated by the mTOR pathway. For many of them, ribosome occupancy dropped 3-fold or even more. Moreover, with age, ribosome coverage gradually decreased in the vicinity of start codons and increased near stop codons, revealing complex age-related changes in the translation process. Taken together, our results reveal systematic and multi-dimensional deregulation in protein synthesis, showing how this major cellular process declines with age.

scholarly journals Effects of Tranilast on the Urinary Excretion of Kynurenic and Quinolinic Acid under Conditions of L Tryptophan Loading

2013 ◽  
Vol 6 ◽  
pp. IJTR.S12797 ◽  
Author(s):  
Rowland R. Noakes
Keyword(s):  
Urinary Excretion ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Competitive Inhibitor ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Autoimmune Response ◽  
Current Therapy ◽  
Indoleamine 2 ◽  
Hydroxyanthranilic Acid

The pathogenesis of morphea and other cutaneous sclerosing disorders remain poorly understood. Although they are considered to be autoimmune disorders, abnormal tryptophan metabolism may be involved. Current therapy is directed to supressing the autoimmune response. Demonstration of a therapeutic response to manipulation of the kynurenine pathway would both support a role for abnormal tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3-hydroxyanthranilic acid derivative known to target the kynurenine pathway. The aim of this study was to see if tranilast lowered the urinary excretion of the kynurenine metabolites kynurenic and quinolinic acid under condition of L tryptophan loading in a volunteer. Mean baseline value for kynurenic acid and quinolinic acid were 1.1 and 2.1 mmol/mol creatinine, respectively. This rose to 5.6 and 3.8 mmol/mol creatinine respectively under conditions of L tryptophan loading 2 grams daily. Adding 1 g of tranilast daily lowered the values to 2.0 and 2.9 mmol/mol creatinine, respectively. These data suggest that tranilast acts as a competitive inhibitor of either indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3 di-oxygenase (TDO) or both. As it involved only 1 subject, the results may not be representative of the larger population and must be considered preliminary.

scholarly journals Tryptophan Metabolism in Rat Liver after Administration of Tryptophan, Kynurenine Metabolites, and Kynureninase Inhibitors

2016 ◽  
Vol 9 ◽  
pp. IJTR.S38190 ◽  
Author(s):  
Abdulla A.-B. Badawy ◽  
Samina Bano
Keyword(s):  
Rat Liver ◽  
Immune Activation ◽  
Kynurenic Acid ◽  
Chronic Administration ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Disease States ◽  
Metabolite Concentrations ◽  
Hydroxyanthranilic Acid ◽  
Stimulation Of

Rat liver tryptophan (Trp), kynurenine pathway metabolites, and enzymes deduced from product/substrate ratios were assessed following acute and/or chronic administration of kynurenic acid (KA), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), Trp, and the kynureninase inhibitors benserazide (BSZ) and carbidopa (CBD). KA activated Trp 2,3-dioxygenase (TDO), possibly by increasing liver 3-HAA, but inhibited kynurenine aminotransferase (KAT) and kynureninase activities with 3-HK as substrate. 3-HK inhibited kynureninase activity from 3-HK. 3-HAA stimulated TDO, but inhibited kynureninase activity from K and 3-HK. Trp (50 mg/kg) increased kynurenine metabolite concentrations and KAT from K, and exerted a temporary stimulation of TDO. The kynureninase inhibitors BSZ and CBD also inhibited KAT, but stimulated TDO. BSZ abolished or strongly inhibited the Trp-induced increases in liver Trp and kynurenine metabolites. The potential effects of these changes in conditions of immune activation, schizophrenia, and other disease states are discussed.

scholarly journals Stochastic Resonance Activity Influences Serum Tryptophan Metabolism in Healthy Human Subjects

2011 ◽  
Vol 4 ◽  
pp. IJTR.S7986 ◽  
Author(s):  
Berthold Kepplinger ◽  
Halina Baran ◽  
Brenda Sedlnitzky-Semler ◽  
Nagy-Roland Badawi ◽  
Helene Erhart
Keyword(s):  
Stochastic Resonance ◽  
Anthranilic Acid ◽  
Kynurenic Acid ◽  
Human Subjects ◽  
Serum Levels ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Healthy Human ◽  
Neuropsychiatric Diseases ◽  
Exercise Activity

Background Stochastic resonance therapy (SRT) is used for rehabilitation of patients with various neuropsychiatric diseases. An alteration in tryptophan metabolism along the kynurenine pathway has been identified in the central and peripheral nervous systems in patients with neuroinflammatory and neurodegenerative diseases and during the aging process. This study investigated the effect of SRT as an exercise activity on serum tryptophan metabolites in healthy subjects. Methods Serum L-tryptophan, L-kynurenine, kynurenic acid, and anthranilic acid levels were measured one minute before SRT and at one, 5, 15, 30, and 60 minutes after SRT. We found that SRT affected tryptophan metabolism. Serum levels of L-tryptophan, L-kynurenine, and kynurenic acid were significantly reduced for up to 60 minutes after SRT. Anthranilic acid levels were characterized by a moderate, non significant transient decrease for up to 15 minutes, followed by normalization at 60 minutes. Tryptophan metabolite ratios were moderately altered, suggesting activation of metabolism after SRT. Lowering of tryptophan would generally involve activation of tryptophan catabolism and neurotransmitter, protein, and bone biosynthesis. Lowering of kynurenic acid by SRT might be relevant for improving symptoms in patients with neuropsychiatric disorders, such as Parkinson's disease, Alzheimer's disease, schizophrenia, and depression, as well as certain pain conditions.

Age-related changes in kynurenic acid production in rat brain

1992 ◽  
Vol 588 (1) ◽  
pp. 1-5 ◽  
Author(s):  
Jan Bert P. Gramsbergen ◽  
Werner Schmidt ◽  
Waldemar A. Turski ◽  
Robert Schwarcz
Keyword(s):  
Rat Brain ◽  
Acid Production ◽  
Kynurenic Acid ◽  
Age Related ◽  
Age Related Changes

scholarly journals Sexual dimorphism in age-related changes in the expression of genes involved into regulation of calcium metabolism in aorta and myocardium of rats

2020 ◽  
Author(s):  
Lubov Kozhevnikova ◽  
Irina Sukhanova ◽  
NP Semenova ◽  
Alena Efimova ◽  
Sergey Kryzhanovskii
Keyword(s):  
Left Ventricle ◽  
Left Atrium ◽  
Right Atrium ◽  
Transcriptional Activity ◽  
Expression Of Genes ◽  
Age Related ◽  
Mrna Content ◽  
Old Rats ◽  
The Right ◽  
Age Related Changes

Abstract Age is the main risk factor for cardiovascular disease development. Understanding of mechanism underlying the vascular and myocardial ageing is necessary both for prevention and for treatment of age-associated diseases. The research aimed to evaluate age-related changes in the transcriptional activity of genes involved in the regulation of Ca2 + signalling – IP3R, RyR, and modulators of their activity CaM and Epac in blood vessels and myocardium of rats of both sexes.Gene expression was evaluated according to the mRNA content of the test protein relative to the β-actin mRNA content. It is proven that rats of both sexes develop unidirectional changes in the expression of genes encoding IP3Rs and RyR2, and different ones in the expression of protein genes modulating their activity – CaM and Epac depending on the sex of animals. In the vessels of old rats (24 months) of both sexes the relative level of mRNA for IP3R type 2 and 3 was reduced and not changed for IP3R1, and significantly increased for RyR2 receptors compared to these indicators in young rats (4 months). In the aorta of old females the relative mRNA content for CaM and Epac1 was reduced and not changed for Epac2. On the contrary, the expression of Epac1 and Epac2 was increased by 67% and 50% respectively compared to similar indicators in young rats (4 months) and rests unchanged for CaM which indicates gender differences in the violation of subtle mechanisms for modulating the activity of RyR2 and IP3Rs in blood vessels. Old rats showed significant changes in myocardium. In older males, the expression of RyR2,IP3R1,2, 3 increases in the left ventricle, RyR2 and IP3R1 – in the left atrium, and RyR2 and IP3R3 – in the right atrium. Unlike males, the mRNA content for RyR2, IP3R1, 2, 3 was significantly lower in the left ventricle of females than in young animals. High levels of IP3R1 and IP3R3 expression were detected in the right atrium of senior females, and IP3R3 expression was detected in the left atrium. The expression of IP3R2 was unchanged in all parts of the female heart. In the myocardium of old rats of both sexes the expression of CaM and Epac2 proteins increased significantly. The revealed age differences in the transcriptional activity of genes involved in the regulation of intracellular Ca2 + signalling at the level of IP3Rs-and RyR2-mediated mechanisms suggest that with the increasing life expectancy males are significantly more likely to develop myocardial hypertrophy and heart rhythm disorders than females.

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