Editorial

2 pages, 499 KiB

Open AccessEditorial

by Burkhard Poeggeler, Sandeep Kumar Singh, Kumar Sambamurti and Miguel Angelo Pappolla

Int. J. Mol. Sci. 2023, 24(8), 7112; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24087112 - 12 Apr 2023

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This editorial summarizes the eight articles that have been collected for the Special Issue entitled “Tryptophan in Nutrition and Health 2 [...] Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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Research

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14 pages, 1771 KiB

Open AccessCommunication

Tryptophan Hydroxylase-2-Mediated Serotonin Biosynthesis Suppresses Cell Reprogramming into Pluripotent State

by Sergey A. Sinenko, Andrey A. Kuzmin, Elena V. Skvortsova, Sergey V. Ponomartsev, Evgeniya V. Efimova, Michael Bader, Natalia Alenina and Alexey N. Tomilin

Int. J. Mol. Sci. 2023, 24(5), 4862; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054862 - 02 Mar 2023

Cited by 3 | Viewed by 2845

Abstract

The monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has important functions both in the neural system and during embryonic development in mammals. In this study, we set out to investigate whether and how endogenous serotonin affects reprogramming to pluripotency. As serotonin is synthesized from tryptophan [...] Read more.

The monoamine neurotransmitter serotonin (5-hydroxytryptamine, 5-HT) has important functions both in the neural system and during embryonic development in mammals. In this study, we set out to investigate whether and how endogenous serotonin affects reprogramming to pluripotency. As serotonin is synthesized from tryptophan by the rate limiting enzymes tryptophan hydroxylase-1 and -2 (TPH1 and TPH2), we have assessed the reprogramming of TPH1- and/or TPH2-deficient mouse embryonic fibroblasts (MEFs) to induced pluripotent stem cells (iPSCs). The reprogramming of the double mutant MEFs showed a dramatic increase in the efficiency of iPSC generation. In contrast, ectopic expression of TPH2 alone or in conjunction with TPH1 reverted the rate of reprogramming of the double mutant MEFs to the wild-type level and besides, TPH2 overexpression significantly suppressed reprogramming of wild-type MEFs. Our data thus suggest a negative role of serotonin biosynthesis in the reprogramming of somatic cells to a pluripotent state. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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17 pages, 2847 KiB

Open AccessArticle

Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma

by Beáta Hubková, Marcela Valko-Rokytovská, Beáta Čižmárová, Marianna Zábavníková, Mária Mareková and Anna Birková

Int. J. Mol. Sci. 2022, 23(16), 9160; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23169160 - 15 Aug 2022

Cited by 7 | Viewed by 2634

Abstract

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer to evade immune surveillance. Altered tryptophan metabolism was studied in patients with pigmented malignant melanoma confirmed histologically by the anatomic stage grouping for cutaneous melanoma using clinical [...] Read more.

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer to evade immune surveillance. Altered tryptophan metabolism was studied in patients with pigmented malignant melanoma confirmed histologically by the anatomic stage grouping for cutaneous melanoma using clinical staging on the basis of the Breslow thickness of the melanoma, the degree of spread to regional lymph nodes, and by the presence of distant metastasis. (2) Methods: Urinary tryptophan metabolites were detected by RP-HPLC method. (3) Results: In the present work, we provided evidence of altered metabolism of all tryptophan pathways in melanoma patients. (4) Conclusions: Knowledge of the shifted serotonin pathway toward DHICA formation and kynurenine pathway shifted toward NAD⁺ production could serve in the early detection of the disease and the initiation of early treatment of malignant melanoma. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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19 pages, 14638 KiB

Open AccessArticle

UVB Radiation and Selected Tryptophan-Derived AhR Ligands—Potential Biological Interactions in Melanoma Cells

by Katarzyna Walczak, Paulina Kazimierczak, Karolina Szalast and Tomasz Plech

Int. J. Mol. Sci. 2021, 22(14), 7500; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22147500 - 13 Jul 2021

Cited by 12 | Viewed by 2274

Abstract

Excessive UV exposure is considered the major environmental factor in melanoma progression. Human skin is constantly exposed to selected tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, including kynurenine (KYN) and kynurenic acid (KYNA), as they are endogenously produced and present in various tissues and [...] Read more.

Excessive UV exposure is considered the major environmental factor in melanoma progression. Human skin is constantly exposed to selected tryptophan-derived aryl hydrocarbon receptor (AhR) ligands, including kynurenine (KYN) and kynurenic acid (KYNA), as they are endogenously produced and present in various tissues and body fluids. Importantly, recent studies confirmed the biological activity of KYN and KYNA toward melanoma cells in vitro. Thus, in this study, the potential biological interactions between UVB and tryptophan metabolites KYN and KYNA were studied in melanoma A375, SK-MEL-3, and RPMI-7951 cells. It was shown that UVB enhanced the antiproliferative activity of KYN and KYNA in melanoma cells. Importantly, selected tryptophan-derived AhR ligands did not affect the invasiveness of A375 and RPMI-7951 cells; however, the stimulatory effect was observed in SK-MEL-3 cells exposed to UVB. Thus, the effect of tryptophan metabolites on metabolic activity, cell cycle regulation, and cell death in SK-MEL-3 cells exposed to UVB was assessed. In conclusion, taking into account that both UVB radiation and tryptophan-derived AhR ligands may have a crucial effect on skin cancer formation and progression, these results may have a significant impact, revealing the potential biological interactions in melanoma cells in vitro. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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Review

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34 pages, 3100 KiB

Open AccessReview

Non-Invasive Brain Stimulation Effects on Biomarkers of Tryptophan Metabolism: A Scoping Review and Meta-Analysis

by Cristian G. Giron, Tim T. Z. Lin, Rebecca L. D. Kan, Bella B. B. Zhang, Suk Yu Yau and Georg S. Kranz

Int. J. Mol. Sci. 2022, 23(17), 9692; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23179692 - 26 Aug 2022

Cited by 4 | Viewed by 2809

Abstract

Abnormal activation of the kynurenine and serotonin pathways of tryptophan metabolism is linked to a host of neuropsychiatric disorders. Concurrently, noninvasive brain stimulation (NIBS) techniques demonstrate high therapeutic efficacy across neuropsychiatric disorders, with indications for modulated neuroplasticity underlying such effects. We therefore conducted [...] Read more.

Abnormal activation of the kynurenine and serotonin pathways of tryptophan metabolism is linked to a host of neuropsychiatric disorders. Concurrently, noninvasive brain stimulation (NIBS) techniques demonstrate high therapeutic efficacy across neuropsychiatric disorders, with indications for modulated neuroplasticity underlying such effects. We therefore conducted a scoping review with meta-analysis of eligible studies, conforming with the PRISMA statement, by searching the PubMed and Web of Science databases for clinical and preclinical studies that report the effects of NIBS on biomarkers of tryptophan metabolism. NIBS techniques reviewed were electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS), and transcranial direct current stimulation (tDCS). Of the 564 search results, 65 studies were included with publications dating back to 1971 until 2022. The Robust Bayesian Meta-Analysis on clinical studies and qualitative analysis identified general null effects by NIBS on biomarkers of tryptophan metabolism, but moderate evidence for TMS effects on elevating serum serotonin levels. We cannot interpret this as evidence for or against the effects of NIBS on these biomarkers, as there exists several confounding methodological differences in this literature. Future controlled studies are needed to elucidate the effects of NIBS on biomarkers of tryptophan metabolism, an under-investigated question with substantial implications to clinical research and practice. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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15 pages, 1409 KiB

Open AccessReview

Melatonin and the Brain–Heart Crosstalk in Neurocritically Ill Patients—From Molecular Action to Clinical Practice

by Artur Bekała, Włodzimierz Płotek, Dorota Siwicka-Gieroba, Joanna Sołek-Pastuszka, Romuald Bohatyrewicz, Jowita Biernawska, Katarzyna Kotfis, Magdalena Bielacz, Andrzej Jaroszyński and Wojciech Dabrowski

Int. J. Mol. Sci. 2022, 23(13), 7094; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23137094 - 25 Jun 2022

Cited by 7 | Viewed by 3474

Abstract

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain–heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and [...] Read more.

Brain injury, especially traumatic brain injury (TBI), may induce severe dysfunction of extracerebral organs. Cardiac dysfunction associated with TBI is common and well known as the brain–heart crosstalk, which broadly refers to different cardiac disorders such as cardiac arrhythmias, ischemia, hemodynamic insufficiency, and sudden cardiac death, which corresponds to acute disorders of brain function. TBI-related cardiac dysfunction can both worsen the brain damage and increase the risk of death. TBI-related cardiac disorders have been mainly treated symptomatically. However, the analysis of pathomechanisms of TBI-related cardiac dysfunction has highlighted an important role of melatonin in the prevention and treatment of such disorders. Melatonin is a neurohormone released by the pineal gland. It plays a crucial role in the coordination of the circadian rhythm. Additionally, melatonin possesses strong anti-inflammatory, antioxidative, and antiapoptotic properties and can modulate sympathetic and parasympathetic activities. Melatonin has a protective effect not only on the brain, by attenuating its injury, but on extracranial organs, including the heart. The aim of this study was to analyze the molecular activity of melatonin in terms of TBI-related cardiac disorders. Our article describes the benefits resulting from using melatonin as an adjuvant in protection and treatment of brain injury-induced cardiac dysfunction. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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26 pages, 2432 KiB

Open AccessReview

An Emerging Cross-Species Marker for Organismal Health: Tryptophan-Kynurenine Pathway

by Laiba Jamshed, Amrita Debnath, Shanza Jamshed, Jade V. Wish, Jason C. Raine, Gregg T. Tomy, Philippe J. Thomas and Alison C. Holloway

Int. J. Mol. Sci. 2022, 23(11), 6300; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116300 - 04 Jun 2022

Cited by 19 | Viewed by 4034

Abstract

Tryptophan (TRP) is an essential dietary amino acid that, unless otherwise committed to protein synthesis, undergoes metabolism via the Tryptophan-Kynurenine (TRP-KYN) pathway in vertebrate organisms. TRP and its metabolites have key roles in diverse physiological processes including cell growth and maintenance, immunity, disease [...] Read more.

Tryptophan (TRP) is an essential dietary amino acid that, unless otherwise committed to protein synthesis, undergoes metabolism via the Tryptophan-Kynurenine (TRP-KYN) pathway in vertebrate organisms. TRP and its metabolites have key roles in diverse physiological processes including cell growth and maintenance, immunity, disease states and the coordination of adaptive responses to environmental and dietary cues. Changes in TRP metabolism can alter the availability of TRP for protein and serotonin biosynthesis as well as alter levels of the immune-active KYN pathway metabolites. There is now considerable evidence which has shown that the TRP-KYN pathway can be influenced by various stressors including glucocorticoids (marker of chronic stress), infection, inflammation and oxidative stress, and environmental toxicants. While there is little known regarding the role of TRP metabolism following exposure to environmental contaminants, there is evidence of linkages between chemically induced metabolic perturbations and altered TRP enzymes and KYN metabolites. Moreover, the TRP-KYN pathway is conserved across vertebrate species and can be influenced by exposure to xenobiotics, therefore, understanding how this pathway is regulated may have broader implications for environmental and wildlife toxicology. The goal of this narrative review is to (1) identify key pathways affecting Trp-Kyn metabolism in vertebrates and (2) highlight consequences of altered tryptophan metabolism in mammals, birds, amphibians, and fish. We discuss current literature available across species, highlight gaps in the current state of knowledge, and further postulate that the kynurenine to tryptophan ratio can be used as a novel biomarker for assessing organismal and, more broadly, ecosystem health. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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19 pages, 888 KiB

Open AccessReview

Biological Effects of Indole-3-Propionic Acid, a Gut Microbiota-Derived Metabolite, and Its Precursor Tryptophan in Mammals’ Health and Disease

by Piotr Konopelski and Izabella Mogilnicka

Int. J. Mol. Sci. 2022, 23(3), 1222; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23031222 - 22 Jan 2022

Cited by 64 | Viewed by 9136

Abstract

Actions of symbiotic gut microbiota are in dynamic balance with the host’s organism to maintain homeostasis. Many different factors have an impact on this relationship, including bacterial metabolites. Several substrates for their synthesis have been established, including tryptophan, an exogenous amino acid. Many [...] Read more.

Actions of symbiotic gut microbiota are in dynamic balance with the host’s organism to maintain homeostasis. Many different factors have an impact on this relationship, including bacterial metabolites. Several substrates for their synthesis have been established, including tryptophan, an exogenous amino acid. Many biological processes are influenced by the action of tryptophan and its endogenous metabolites, serotonin, and melatonin. Recent research findings also provide evidence that gut bacteria-derived metabolites of tryptophan share the biological effects of their precursor. Thus, this review aims to investigate the biological actions of indole-3-propionic acid (IPA), a gut microbiota-derived metabolite of tryptophan. We searched PUBMED and Google Scholar databases to identify pre-clinical and clinical studies evaluating the impact of IPA on the health and pathophysiology of the immune, nervous, gastrointestinal and cardiovascular system in mammals. IPA exhibits a similar impact on the energetic balance and cardiovascular system to its precursor, tryptophan. Additionally, IPA has a positive impact on a cellular level, by preventing oxidative stress injury, lipoperoxidation and inhibiting synthesis of proinflammatory cytokines. Its synthesis can be diminished in the presence of different risk factors of atherosclerosis. On the other hand, protective factors, such as the introduction of a Mediterranean diet, tend to increase its plasma concentration. IPA seems to be a promising new target, linking gut health with the cardiovascular system. Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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21 pages, 1866 KiB

Open AccessReview

Tryptophan: A Unique Role in the Critically Ill

by Marcela Kanova and Pavel Kohout

Int. J. Mol. Sci. 2021, 22(21), 11714; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111714 - 28 Oct 2021

Cited by 23 | Viewed by 6939

Abstract

Tryptophan is an essential amino acid whose metabolites play key roles in diverse physiological processes. Due to low reserves in the body, especially under various catabolic conditions, tryptophan deficiency manifests itself rapidly, and both the serotonin and kynurenine pathways of metabolism are clinically [...] Read more.

Tryptophan is an essential amino acid whose metabolites play key roles in diverse physiological processes. Due to low reserves in the body, especially under various catabolic conditions, tryptophan deficiency manifests itself rapidly, and both the serotonin and kynurenine pathways of metabolism are clinically significant in critically ill patients. In this review, we highlight these pathways as sources of serotonin and melatonin, which then regulate neurotransmission, influence circadian rhythm, cognitive functions, and the development of delirium. Kynurenines serve important signaling functions in inter-organ communication and modulate endogenous inflammation. Increased plasma kynurenine levels and kynurenine-tryptophan ratios are early indicators for the development of sepsis. They also influence the regulation of skeletal muscle mass and thereby the development of polyneuromyopathy in critically ill patients. The modulation of tryptophan metabolism could help prevent and treat age-related disease with low grade chronic inflammation as well as post intensive care syndrome in all its varied manifestations: cognitive decline (including delirium or dementia), physical impairment (catabolism, protein breakdown, loss of muscle mass and tone), and mental impairment (depression, anxiety or post-traumatic stress disorder). Full article

(This article belongs to the Special Issue Tryptophan in Nutrition and Health 2.0)

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