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Fulltext Tryptophan metabolism-related gene expression patterns: unveiling prognostic insights and immune landscapes in uveal melanoma

Wang J, Zhao T, Li B, Wei W

Aging (Albany NY), 2023 Oct 13;15(20):11201-11216.
PMID: 37844995 DOI: 10.18632/aging.205122

Uveal melanoma (UVM) remains the leading intraocular malignancy in adults, with a poor prognosis for those with metastatic disease. Tryptophan metabolism plays a pivotal role in influencing cancerous properties and modifying the tumor's immune microenvironment. In this study, we explore the relationship between tryptophan metabolism-related gene (TRMG) expression and the various features of UVM, including prognosis and tumor microenvironment. Our analysis included 143 patient samples sourced from public databases. Using K-means clustering, we categorized UVM patients into two distinct clusters. Further, we developed a prognostic model based on five essential genes, effectively distinguishing between low-risk and high-risk patients. This distinction underscores the importance of TRMGs in UVM prognostication. Combining TRMG data with gender to create nomograms demonstrated exceptional accuracy in predicting UVM patient outcomes. Moreover, our analysis reveals correlations between risk assessments and immune cell infiltrations. Notably, the low-risk group displayed a heightened potential response to immune checkpoint inhibitors. In conclusion, our findings underscore the dynamic relationship between TRMG expression and various UVM characteristics, presenting a novel prognostic framework centered on TRMGs. The deep connection between TRMGs and UVM's tumor immune microenvironment emphasizes the crucial role of tryptophan metabolism in shaping the immune landscape. Such understanding paves the way for designing targeted immunotherapy strategies for UVM patients.

Matched MeSH terms: Tryptophan*
The Cytokines CXCL10 and CCL2 and the Kynurenine Metabolite Anthranilic Acid Accurately Predict Patients at Risk of Developing Dengue With Warning Signs

Jusof FF, Lim CK, Aziz FN, Soe HJ, Raju CS, Sekaran SD, et al.

J Infect Dis, 2022 Nov 28;226(11):1964-1973.
PMID: 35767283 DOI: 10.1093/infdis/jiac273

BACKGROUND: The resolution or aggravation of dengue infection depends on the patient's immune response during the critical phase. Cytokines released by immune cells increase with the worsening severity of dengue infections. Cytokines activate the kynurenine pathway (KP) and the extent of KP activation then influences disease severity.
METHODS: KP metabolites and cytokines in plasma samples of patients with dengue infection (dengue without warning signs [DWS-], dengue with warning signs [DWS+], or severe dengue) were analyzed. Cytokines (interferon gamma [IFN-ɣ], tumor necrosis factor, interleukin 6, CXCL10/interferon-inducile protein 10 [IP-10], interleukin 18 [IL-18], CCL2/monocyte chemoattractant protein-1 [MCP-1], and CCL4/macrophage inflammatory protein-1beta [MIP-1β] were assessed by a Human Luminex Screening Assay, while KP metabolites (tryptophan, kynurenine, anthranilic acid [AA], picolinic acid, and quinolinic acid) were assessed by ultra-high-performance liquid chromatography and Gas Chromatography Mass Spectrophotometry [GCMS] assays.
RESULTS: Patients with DWS+ had increased activation of the KP where kynurenine-tryptophan ratio, anthranilic acid, and picolinic acid were elevated. These patients also had higher levels of the cytokines IFN-ɣ, CXCL10, CCL4, and IL-18 than those with DWS-. Further receiver operating characteristic analysis identified 3 prognostic biomarker candidates, CXCL10, CCL2, and AA, which predicted patients with higher risks of developing DWS+ with an accuracy of 97%.
CONCLUSIONS: The data suggest a unique biochemical signature in patients with DWS+. CXCL10 and CCL2 together with AA are potential prognostic biomarkers that discern patients with higher risk of developing DWS+ at earlier stages of infection.

Matched MeSH terms: Tryptophan/metabolism
The Lichen Flavin-Dependent Halogenase, DnHal: Identification, Heterologous Expression and Functional Characterization

Hasan NS, Ling JG, Bakar MFA, Seman WMKW, Murad AMA, Bakar FDA, et al.

Appl Biochem Biotechnol, 2023 Nov;195(11):6708-6736.
PMID: 36913095 DOI: 10.1007/s12010-022-04304-w

Enzymatic halogenation captures scientific interest considering its feasibility in modifying compounds for chemical diversity. Currently, majority of flavin-dependent halogenases (F-Hals) were reported from bacterial origin, and as far as we know, none from lichenized fungi. Fungi are well-known producers of halogenated compounds, so using available transcriptomic dataset of Dirinaria sp., we mined for putative gene encoding for F-Hal. Phylogenetic-based classification of the F-Hal family suggested a non-tryptophan F-Hals, similar to other fungal F-Hals, which mainly act on aromatic compounds. However, after the putative halogenase gene from Dirinaria sp., dnhal was codon-optimized, cloned, and expressed in Pichia pastoris, the ~63 kDa purified enzyme showed biocatalytic activity towards tryptophan and an aromatic compound methyl haematommate, which gave the tell-tale isotopic pattern of a chlorinated product at m/z 239.0565 and 241.0552; and m/z 243.0074 and 245.0025, respectively. This study is the start of understanding the complexities of lichenized fungal F-hals and its ability to halogenate tryptophan and other aromatic. compounds which can be used as green alternatives for biocatalysis of halogenated compounds.

Matched MeSH terms: Tryptophan/metabolism
Fulltext A tryptophan metabolite made by a gut microbiome eukaryote induces pro-inflammatory T cells

Wojciech L, Png CW, Koh EY, Kioh DYQ, Deng L, Wang Z, et al.

EMBO J, 2023 Nov 02;42(21):e112963.
PMID: 37743772 DOI: 10.15252/embj.2022112963

The large intestine harbors microorganisms playing unique roles in host physiology. The beneficial or detrimental outcome of host-microbiome coexistence depends largely on the balance between regulators and responder intestinal CD4+ T cells. We found that ulcerative colitis-like changes in the large intestine after infection with the protist Blastocystis ST7 in a mouse model are associated with reduction of anti-inflammatory Treg cells and simultaneous expansion of pro-inflammatory Th17 responders. These alterations in CD4+ T cells depended on the tryptophan metabolite indole-3-acetaldehyde (I3AA) produced by this single-cell eukaryote. I3AA reduced the Treg subset in vivo and iTreg development in vitro by modifying their sensing of TGFβ, concomitantly affecting recognition of self-flora antigens by conventional CD4+ T cells. Parasite-derived I3AA also induces over-exuberant TCR signaling, manifested by increased CD69 expression and downregulation of co-inhibitor PD-1. We have thus identified a new mechanism dictating CD4+ fate decisions. The findings thus shine a new light on the ability of the protist microbiome and tryptophan metabolites, derived from them or other sources, to modulate the adaptive immune compartment, particularly in the context of gut inflammatory disorders.

Matched MeSH terms: Tryptophan/metabolism
Fulltext Isolation and characterization of cyclo-(tryptophanyl-prolyl) and chloramphenicol from Streptomyces sp. SUK 25 with antimethicillin-resistant Staphylococcus aureus activity

Alshaibani MM, Jalil J, Sidik NM, Edrada-Ebel R, Zin NM

Drug Des Devel Ther, 2016;10:1817-27.
PMID: 27330275 DOI: 10.2147/DDDT.S101212

BACKGROUND: Zingiber spectabile, commonly known as Beehive Ginger, is used as an ethnobotanical plant in many countries as an appetizer or to treat stomachache, toothache, muscle sprain, and as a cure for swelling, sores and cuts. This is the first report of isolation of Streptomyces strain from the root of this plant. Strain Universiti Kebangsaan 25 (SUK 25) has a very high activity to produce secondary metabolites against methicillin-resistant Staphylococcus aureus (MRSA), which is associated with high morbidity and mortality rates due to acquired multidrug resistance genes and causes medication failure in some clinical cases worldwide. Phylogenetic analysis based on the 16S ribosomal RNA gene sequence exhibited that the most closely related strain was Streptomyces omiyaensis NBRC 13449T (99.0% similarity).
AIM: This study was conducted to carry out the extraction, identification, and biological evaluation of active metabolites isolated from SUK 25 against three MRSA strains, namely, MRSA ATCC 43300, MRSA ATCC 33591, and MRSA ATCC 49476.
MATERIALS AND METHODS: The production of secondary metabolites by this strain was optimized through Thronton's media. Isolation, purification, and identification of the bioactive compounds were carried out using reversed-phase high-performance liquid chromatography, high-resolution mass spectrometry, Fourier transform infrared, and one-dimensional and two-dimensional nuclear magnetic resonance.
RESULTS: During screening procedure, SUK 25 exhibited good antimicrobial potential against several strains of MRSA. The best biological activity was shown from fraction number VII and its subfractions F2 and F3 with minimum inhibitory concentration values at 16 µg/mL and 8 µg/mL, respectively. These two subfractions were identified as diketopiperazine cyclo-(tryptophanyl-prolyl) and chloramphenicol.
CONCLUSION: On the basis of obtained results, SUK 25 isolated from Z. spectabile can be regarded as a new valuable source to produce secondary metabolites against bacteria, especially MRSA.

Matched MeSH terms: Tryptophan/analogs & derivatives*; Tryptophan/isolation & purification; Tryptophan/pharmacology; Tryptophan/chemistry
Fulltext Tryptophan-catabolizing enzymes - party of three

Ball HJ, Jusof FF, Bakmiwewa SM, Hunt NH, Yuasa HJ

Front Immunol, 2014;5:485.
PMID: 25346733 DOI: 10.3389/fimmu.2014.00485

Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are tryptophan-degrading enzymes that have independently evolved to catalyze the first step in tryptophan catabolism via the kynurenine pathway (KP). The depletion of tryptophan and formation of KP metabolites modulates the activity of the mammalian immune, reproductive, and central nervous systems. IDO and TDO enzymes can have overlapping or distinct functions depending on their expression patterns. The expression of TDO and IDO enzymes in mammals differs not only by tissue/cellular localization but also by their induction by distinct stimuli. To add to the complexity, these genes also have undergone duplications in some organisms leading to multiple isoforms of IDO or TDO. For example, many vertebrates, including all mammals, have acquired two IDO genes via gene duplication, although the IDO1-like gene has been lost in some lower vertebrate lineages. Gene duplications can allow the homologs to diverge and acquire different properties to the original gene. There is evidence for IDO enzymes having differing enzymatic characteristics, signaling properties, and biological functions. This review analyzes the evolutionary convergence of IDO and TDO enzymes as tryptophan-catabolizing enzymes and the divergent evolution of IDO homologs to generate an enzyme family with diverse characteristics not possessed by TDO enzymes, with an emphasis on the immune system.

Matched MeSH terms: Tryptophan; Tryptophan Oxygenase
Fulltext Altered Tryptophan-Kynurenine Pathway in Delirium: A Review of the Current Literature

Phing AH, Makpol S, Nasaruddin ML, Wan Zaidi WA, Ahmad NS, Embong H

Int J Mol Sci, 2023 Mar 15;24(6).
PMID: 36982655 DOI: 10.3390/ijms24065580

Delirium, a common form of acute brain dysfunction, is associated with increased morbidity and mortality, especially in older patients. The underlying pathophysiology of delirium is not clearly understood, but acute systemic inflammation is known to drive delirium in cases of acute illnesses, such as sepsis, trauma, and surgery. Based on psychomotor presentations, delirium has three main subtypes, such as hypoactive, hyperactive, and mixed subtype. There are similarities in the initial presentation of delirium with depression and dementia, especially in the hypoactive subtype. Hence, patients with hypoactive delirium are frequently misdiagnosed. The altered kynurenine pathway (KP) is a promising molecular pathway implicated in the pathogenesis of delirium. The KP is highly regulated in the immune system and influences neurological functions. The activation of indoleamine 2,3-dioxygenase, and specific KP neuroactive metabolites, such as quinolinic acid and kynurenic acid, could play a role in the event of delirium. Here, we collectively describe the roles of the KP and speculate on its relevance in delirium.

Matched MeSH terms: Tryptophan/metabolism
Investigation of the links between heterocyst and biohydrogen production by diazotrophic cyanobacterium A. variabilis ATCC 29413

Salleh SF, Kamaruddin A, Uzir MH, Karim KA, Mohamed AR

Arch Microbiol, 2016 Mar;198(2):101-13.
PMID: 26521065 DOI: 10.1007/s00203-015-1164-6

This work investigates the effect of heterocyst toward biohydrogen production by A. variabilis. The heterocyst frequency was artificially promoted by adding an amino acid analog, in this case DL-7-azatryptophan into the growth medium. The frequency of heterocyst differentiation was found to be proportional to the concentration of azatryptophan (0-25 µM) in the medium. Conversely, the growth and nitrogenase activity were gradually suppressed. In addition, there was also a distinct shortening of the cells filaments and detachment of heterocyst from the vegetative cells. Analysis on the hydrogen production performance revealed that both the frequency and distribution of heterocyst in the filaments affected the rate of hydrogen production. The highest hydrogen production rate and yield (41 µmol H2 mg chl a(-1) h(-1) and 97 mL H2 mg chl a(-1), respectively) were achieved by cells previously grown in 15 µM of azatryptophan with 14.5 % of heterocyst frequency. The existence of more isolated heterocyst has been shown to cause a relative loss in nitrogenase activity thus lowering the hydrogen production rate.

Matched MeSH terms: Tryptophan
Quinine interactions with tryptophan and tyrosine in malaria patients, and implications for quinine responses in the clinical setting

Islahudin F, Pleass RJ, Avery SV, Ting KN

J Antimicrob Chemother, 2012 Oct;67(10):2501-5.
PMID: 22763566 DOI: 10.1093/jac/dks253

OBJECTIVES: Recent work with the yeast model revealed that the antiprotozoal drug quinine competes with tryptophan for uptake via a common transport protein, causing cellular tryptophan starvation. In the present work, it was hypothesized that similar interactions may occur in malaria patients receiving quinine therapy.
PATIENTS AND METHODS: A direct observational study was conducted in which plasma levels of drug and amino acids (tryptophan, tyrosine and phenylalanine) were monitored during quinine treatment of malaria patients with Plasmodium falciparum infections.
RESULTS: Consistent with competition for uptake from plasma into cells, plasma tryptophan and tyrosine levels increased ≥2-fold during quinine therapy. Plasma quinine levels in individual plasma samples were significantly and positively correlated with tryptophan and tyrosine in the same samples. Control studies indicated no effect on phenylalanine. Chloroquine treatment of Plasmodium vivax-infected patients did not affect plasma tryptophan or tyrosine. During quinine treatment, plasma tryptophan was significantly lower (and quinine significantly higher) in patients experiencing adverse drug reactions.
CONCLUSIONS: Plasma quinine levels during therapy are related to patient tryptophan and tyrosine levels, and these interactions can determine patient responses to quinine. The study also highlights the potential for extrapolating insights directly from the yeast model to human malaria patients.

Matched MeSH terms: Tryptophan/antagonists & inhibitors*; Tryptophan/metabolism
Fulltext Degree of hydrolysis and free tryptophan content of Skipjack Tuna (Katsuwonus pelamis) protein hydrolysates produced with different type of industrial proteases

Herpandi, Huda, N., Rosma, A., Wan Nadiah W. A.

International Food Research Journal, 2012;19(3):863-867.
MyJurnal

Protein-rich by-products from the canning industry, especially dark flesh of skipjack, have limited uses due to several factors such as darken color, susceptibility to oxidation and off flavour. Protein hydrolysates from skipjack dark flesh was produced with different type of industrial proteases (Alcalase®2.4L FG, Protamex®, Neutrase®1.5MG and Flavourzyme®500MG) for 60, 120, 180 and 240 min with level of proteases used of 0.5, 1, 1.5 and 2% per weight of raw material. The degree of hydrolysis and free tryptophan content of hydrolysate were investigated. The results shows longer time with higher concentration of enzyme has increased the degree of hydrolysis. Alcalase®2.4L FG had the highest degree of hydrolysis among all proteases followed by Protamex®, Flavourzyme®500MG and Neutrase® 1.5MG. All enzymes increase free tryptophan content linearly with the increament of protease enzyme level. The longer the hydrolysis time, the higher the content of free tryptophan produced.

Matched MeSH terms: Tryptophan
In-Silico Characterization of Glycosyl Hydrolase Family 1 β-Glucosidase from Trichoderma asperellum UPM1

Mohamad Sobri MF, Abd-Aziz S, Abu Bakar FD, Ramli N

Int J Mol Sci, 2020 Jun 04;21(11).
PMID: 32512945 DOI: 10.3390/ijms21114035

β-glucosidases (Bgl) are widely utilized for releasing non-reducing terminal glucosyl residues. Nevertheless, feedback inhibition by glucose end product has limited its application. A noticeable exception has been found for β-glucosidases of the glycoside hydrolase (GH) family 1, which exhibit tolerance and even stimulation by glucose. In this study, using local isolate Trichoderma asperellum UPM1, the gene encoding β-glucosidase from GH family 1, hereafter designated as TaBgl2, was isolated and characterized via in-silico analyses. A comparison of enzyme activity was subsequently made by heterologous expression in Escherichia coli BL21(DE3). The presence of N-terminal signature, cis-peptide bonds, conserved active site motifs, non-proline cis peptide bonds, substrate binding, and a lone conserved stabilizing tryptophan (W) residue confirms the identity of Trichoderma sp. GH family 1 β-glucosidase isolated. Glucose tolerance was suggested by the presence of 14 of 22 known consensus residues, along with corresponding residues L167 and P172, crucial in the retention of the active site's narrow cavity. Retention of 40% of relative hydrolytic activity on ρ-nitrophenyl-β-D-glucopyranoside (ρNPG) in a concentration of 0.2 M glucose was comparable to that of GH family 1 β-glucosidase (Cel1A) from Trichoderma reesei. This research thus underlines the potential in the prediction of enzymatic function, and of industrial importance, glucose tolerance of family 1 β-glucosidases following relevant in-silico analyses.

Matched MeSH terms: Tryptophan
Light exposure accelerates oxidative protein polymerization in beef stored in high oxygen atmosphere

Zainudin MAM, Poojary MM, Jongberg S, Lund MN

Food Chem, 2019 Nov 30;299:125132.
PMID: 31299519 DOI: 10.1016/j.foodchem.2019.125132

Protein oxidation of beef patties stored in high oxygen modified atmosphere packaging for 9 days was investigated. Meat was either stored in the dark, under light, or in the dark with addition of FeCl2/H2O2/myoglobin (forced oxidation). SDS-PAGE analysis showed high degree of protein polymerization for meat exposed to light, compared to the other samples. Light exposure induced reducible (disulfide) and non-reducible cross-links, while mainly disulfides were formed in meat stored in the dark. Light exposure was responsible for 58% loss of free thiols (Cys residues). No significant loss of other amino acid residues was observed and none of the most common oxidation products of tryptophan, tyrosine, and phenylalanine were detected. Intrinsic fluorescence measurements of tryptophan showed 27% loss in samples exposed to light, which was ascribed to loss of protein solubility via protein polymerization rather than tryptophan oxidation. Protein carbonyls were mainly detected in forced oxidized samples at Day 0.

Matched MeSH terms: Tryptophan/chemistry
Fulltext Amino acid compounds released by the giant freshwater prawn Macrobrachium rosenbergii during ecdysis: a factor attracting cannibalistic behaviour?

Juneta-Nor AS, Noordin NM, Azra MN, Ma HY, Husin NM, Ikhwanuddin M

J Zhejiang Univ Sci B, 2020 10 13;21(10):823-834.
PMID: 33043647 DOI: 10.1631/jzus.B2000126

Ecdysis is a common phenomenon that happens throughout the life phase of the giant freshwater prawn Macrobrachium rosenbergii. It is vital to better understand the correlation between cannibalism and biochemical compound that exists during the moulting process. The objective of the present study was to determine the amino acid profile released by M. rosenbergii during the ecdysis process that promotes cannibalism. To accomplish this, changes in amino acid levels (total amino acid (TAA) and free amino acid (FAA)) of tissue muscle, exoskeleton, and sample water of culture medium from the moulting (E-stage) and non-moulting (C-stage) prawns were analysed using high-performance liquid chromatography (HPLC). Comparison study revealed that among the TAA compounds, proline and sarcosine of tissues from moulting prawn were found at the highest levels. The level of FAA from water that contains moulting prawns (E-stage) was dominated by tryptophan and proline. Significant values obtained in the present study suggested that these amino acid compounds act as a chemical cue to promote cannibalism in M. rosenbergii during ecdysis. The knowledge of compositions and compounds that were released during the moulting process should be helpful for better understanding of the mechanism and chemical cues that play roles on triggering cannibalism, and also for future dietary manipulation to improve feeding efficiencies and feeding management, which indirectly impacts productivity and profitability.

Matched MeSH terms: Tryptophan/chemistry
Fulltext Rapid Evaluation and Optimization of Medium Components Governing Tryptophan Production by Pediococcus acidilactici TP-6 Isolated from Malaysian Food via Statistical Approaches

Lim YH, Foo HL, Loh TC, Mohamad R, Abdul Rahim R

Molecules, 2020 Feb 11;25(4).
PMID: 32054138 DOI: 10.3390/molecules25040779

Tryptophan is one of the most extensively used amino acids in livestock industry owing to its effectiveness in enhancing the growth performance of animals. Conventionally, the production of tryptophan relies heavily on genetically modified Escherichia coli but its pathogenicity is a great concern. Our recent study demonstrated that a lactic acid bacterium (LAB), Pediococcus acidilactici TP-6 that isolated from Malaysian food was a promising tryptophan producer. However, the tryptophan production must enhance further for viable industrial application. Hence, the current study evaluated the effects of medium components and optimized the medium composition for tryptophan production by P. acidilactici TP-6 statistically using Plackett-Burman Design, and Central Composite Design. The optimized medium containing molasses (14.06 g/L), meat extract (23.68 g/L), urea (5.56 g/L) and FeSO4 (0.024 g/L) significantly enhanced the tryptophan production by 150% as compared to the control de Man, Rogosa and Sharpe medium. The findings obtained in this study revealed that rapid evaluation and effective optimization of medium composition governing tryptophan production by P. acidilactici TP-6 were feasible via statistical approaches. Additionally, the current findings reveal the potential of utilizing LAB as a safer alternative tryptophan producer and provides insight for future exploitation of various amino acid productions by LAB.

Matched MeSH terms: Tryptophan/biosynthesis*
Fulltext Tryptophan-metabolizing gut microbes regulate adult neurogenesis via the aryl hydrocarbon receptor

Wei GZ, Martin KA, Xing PY, Agrawal R, Whiley L, Wood TK, et al.

Proc Natl Acad Sci U S A, 2021 Jul 06;118(27).
PMID: 34210797 DOI: 10.1073/pnas.2021091118

While modulatory effects of gut microbes on neurological phenotypes have been reported, the mechanisms remain largely unknown. Here, we demonstrate that indole, a tryptophan metabolite produced by tryptophanase-expressing gut microbes, elicits neurogenic effects in the adult mouse hippocampus. Neurogenesis is reduced in germ-free (GF) mice and in GF mice monocolonized with a single-gene tnaA knockout (KO) mutant Escherichia coli unable to produce indole. External administration of systemic indole increases adult neurogenesis in the dentate gyrus in these mouse models and in specific pathogen-free (SPF) control mice. Indole-treated mice display elevated synaptic markers postsynaptic density protein 95 and synaptophysin, suggesting synaptic maturation effects in vivo. By contrast, neurogenesis is not induced by indole in aryl hydrocarbon receptor KO (AhR-/-) mice or in ex vivo neurospheres derived from them. Neural progenitor cells exposed to indole exit the cell cycle, terminally differentiate, and mature into neurons that display longer and more branched neurites. These effects are not observed with kynurenine, another AhR ligand. The indole-AhR-mediated signaling pathway elevated the expression of β-catenin, Neurog2, and VEGF-α genes, thus identifying a molecular pathway connecting gut microbiota composition and their metabolic function to neurogenesis in the adult hippocampus. Our data have implications for the understanding of mechanisms of brain aging and for potential next-generation therapeutic opportunities.

Matched MeSH terms: Tryptophan/metabolism*
Fulltext The antimalarial drug quinine interferes with serotonin biosynthesis and action

Islahudin F, Tindall SM, Mellor IR, Swift K, Christensen HE, Fone KC, et al.

Sci Rep, 2014 Jan 09;4:3618.
PMID: 24402577 DOI: 10.1038/srep03618

The major antimalarial drug quinine perturbs uptake of the essential amino acid tryptophan, and patients with low plasma tryptophan are predisposed to adverse quinine reactions; symptoms of which are similar to indications of tryptophan depletion. As tryptophan is a precursor of the neurotransmitter serotonin (5-HT), here we test the hypothesis that quinine disrupts serotonin function. Quinine inhibited serotonin-induced proliferation of yeast as well as human (SHSY5Y) cells. One possible cause of this effect is through inhibition of 5-HT receptor activation by quinine, as we observed here. Furthermore, cells exhibited marked decreases in serotonin production during incubation with quinine. By assaying activity and kinetics of the rate-limiting enzyme for serotonin biosynthesis, tryptophan hydroxylase (TPH2), we showed that quinine competitively inhibits TPH2 in the presence of the substrate tryptophan. The study shows that quinine disrupts both serotonin biosynthesis and function, giving important new insight to the action of quinine on mammalian cells.

Matched MeSH terms: Tryptophan Hydroxylase/antagonists & inhibitors
Localization and characterization of val-opsin isoform-expressing cells in the brain of adult zebrafish

Hang CY, Kitahashi T, Parhar IS

J. Comp. Neurol., 2014 Dec 1;522(17):3847-60.
PMID: 25043553 DOI: 10.1002/cne.23645

In addition to vision, light information is used to regulate a range of animal physiology. Such nonimage-forming functions of light are mediated by nonvisual photoreceptors expressed in distinct neurons in the retina and the brain in most vertebrates. A nonvisual photoreceptor vertebrate ancient long opsin (VAL-opsin) possesses two functional isoforms in the zebrafish, encoded by valopa and valopb, which has received little attention. To delineate the neurochemical identities of valop cells and to test for colocalization of the valop isoforms, we used in situ hybridization to characterize the expression of the valop genes along with that of neurotransmitters and a neuropeptide known to be present at the sites of valop expression. Double labeling showed that the thalamic valop population coexpresses valopa and valopb. All the thalamic valop cells overlapped with a GABAergic cell mass that continues from the anterior nucleus to the intercalated thalamic nucleus. A novel valopa cell population found in the superior raphe was serotonergic in nature. A valopb cell population in the Edinger-Westphal nucleus was identified as containing thyrotropin-releasing hormone. Valopb cells localized in the hindbrain intermediate reticular formation were noncholinergic in nature (nonmotorneurons). Thus, the presence of valop cell populations in different brain regions with coexpression of neurotransmitters and neuropeptides and the colocalization of valop isoforms in the thalamic cell population indicate regulatory and functional complexity of VAL-opsin in the brain of the zebrafish.

Matched MeSH terms: Tryptophan Hydroxylase/genetics; Tryptophan Hydroxylase/metabolism
Fulltext Expression of Repressor Element 1 Silencing Transcription Factor (REST) in Serotonin Neurons in the Adult Male Nile Tilapia (Oreochromis niloticus)

Soga T, Nakajima S, Parhar IS

Front Neuroanat, 2020;14:599540.
PMID: 33776659 DOI: 10.3389/fnana.2020.599540

Repressor element-1 silencing transcription factor (REST) is highly expressed in the dorsal raphe where serotonin (5-hydroxytryptamine, 5-HT) neurons are located. REST works as a transcription factor for the 5-HT receptor and tryptophan hydroxylase two-gene expression. We hypothesized that REST is co-expressed in 5-HT neurons, which, if demonstrated, would be useful to understand the mechanism of 5-HT dysfunction-related disorders such as negative emotions and depression. Therefore, the present study was designed to examine the expression of the REST gene in the brain (forebrain, midbrain, and hindbrain) of adult male Nile tilapia (Oreochromis niloticus) using rt-PCR. Besides, using immunocytochemistry, co-localization of the REST gene was examined in 5-HT neurons and with neuronal-/glial-cell markers. We found a high expression of the REST gene in the midbrain region of the dorsal raphe, an area of 5-HT neurons. Double-label immunocytochemistry showed neuron-specific expression of REST co-localized in 5-HT neurons in the dorsal and ventral parts of the periventricular pretectal nucleus, paraventricular organ, and dorsal and medial raphe nucleus. Since midbrain 5-HT neurons express REST, we speculate that REST may control 5-HT neuronal activity related to negative emotions, including depression.

Matched MeSH terms: Tryptophan Hydroxylase
Fulltext Multifunctional Tyrosinase Inhibitor Peptides with Copper Chelating, UV-Absorption and Antioxidant Activities: Kinetic and Docking Studies

Yap PG, Gan CY

Foods, 2021 Mar 22;10(3).
PMID: 33810046 DOI: 10.3390/foods10030675

Nature-derived tyrosinase inhibitors are of great industrial interest. Three monophenolase inhibitor peptides (MIPs) and three diphenolase inhibitor peptides (DIPs) from a previous study were investigated for their in vitro tyrosinase inhibitory effects, mode of inhibition, copper-chelating activity, sun protection factor (SPF) and antioxidant activities. DIP1 was found to be the most potent tyrosinase inhibitor (IC50 = 3.04 ± 0.39 mM), which could be due to the binding interactions between its aromatic amino acid residues (Y2 and D7) with tyrosinase hotspots (H85, V248, H258, H263, F264, R268, V283 and E322) and its ability to chelate copper ion within the substrate-binding pocket. The conjugated planar rings of tyrosine and tryptophan may interact with histidine within the active site to provide stability upon enzyme-peptide binding. This postulation was later confirmed as the Lineweaver-Burk analysis had identified DIP1 as a competitive inhibitor and DIP1 also showed 36.27 ± 1.17% of copper chelating activity. In addition, DIP1 provided the highest SPF value (11.9 ± 0.04) as well as ferric reducing antioxidant power (FRAP) (5.09 ± 0.13 mM FeSO4), 2,2'-azinobis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) (11.34 ± 0.90%) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) (29.14 ± 1.36%) free radical scavenging activities compared to other peptides. These results demonstrated that DIP1 could be a multifunctional anti-tyrosinase agent with pharmaceutical and cosmeceutical applications.

Matched MeSH terms: Tryptophan
Physical properties, storage stability, and consumer acceptability for sourdough bread produced using encapsulated kombucha sourdough starter culture

Mohd Roby BH, Muhialdin BJ, Abadl MMT, Mat Nor NA, Marzlan AA, Lim SAH, et al.

J Food Sci, 2020 Aug;85(8):2286-2295.
PMID: 32691422 DOI: 10.1111/1750-3841.15302

This study aimed to produce sourdough bread using an encapsulated kombucha sourdough starter culture without the addition of baker's yeast. The bioactive metabolites of kombucha sourdough starter and sourdough starter without kombucha were identified using 1 H-NMR analysis with multivariate analysis. The physical properties, including loaf volume, specific loaf volume, firmness, and water activity were determined following standard methods. The shelf life and consumer acceptability of the bread were also being evaluated. The principal component analyses showed the presence of 15 metabolites in kombucha sourdough starter. The major compounds that contributed to the differences from sourdough starter without kombucha were alpha-aminobutyric acid, alanine, acetic acid, riboflavin, pyridoxine, anserine, tryptophan, gluconic acid, and trehalose. The encapsulated kombucha sourdough starter increased the loaf volume (976.7 ± 25.2 mL) and specific loaf volume (4.38 ± 0.12 mL/g) compared to yeast bread. Thus, significant (P

Matched MeSH terms: Tryptophan

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