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  1. Article ; Online: Metabolic control of transcription.

    Taylor, Eric B

    Science (New York, N.Y.)

    2023  Volume 381, Issue 6654, Page(s) 125–126

    Abstract: Light alters histone methylation in plants via nuclear α-ketoglutarate dehydrogenase. ...

    Abstract Light alters histone methylation in plants via nuclear α-ketoglutarate dehydrogenase.
    MeSH term(s) Ketoglutarate Dehydrogenase Complex/genetics ; Methylation ; Protein Processing, Post-Translational ; Transcription, Genetic ; Gene Expression Regulation, Plant ; Arabidopsis/enzymology ; Arabidopsis/genetics
    Chemical Substances Ketoglutarate Dehydrogenase Complex (EC 1.2.4.2)
    Language English
    Publishing date 2023-07-13
    Publishing country United States
    Document type Journal Article
    ZDB-ID 128410-1
    ISSN 1095-9203 ; 0036-8075
    ISSN (online) 1095-9203
    ISSN 0036-8075
    DOI 10.1126/science.adi7577
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  2. Article ; Online: Osmoregulatory Performance among Prickly Sculpin (

    Liu, Shuang / Taylor, Eric B / Richards, Jeffrey G

    Physiological and biochemical zoology : PBZ

    2023  Volume 96, Issue 3, Page(s) 233–246

    Abstract: AbstractDuring the colonization of freshwater by marine fish, adaptation to hypoosmotic conditions may impact their ability to osmoregulate in seawater. The prickly sculpin ( ...

    Abstract AbstractDuring the colonization of freshwater by marine fish, adaptation to hypoosmotic conditions may impact their ability to osmoregulate in seawater. The prickly sculpin (
    MeSH term(s) Animals ; Osmoregulation ; Water-Electrolyte Balance/physiology ; Acclimatization/physiology ; Fishes/physiology ; Seawater ; Lakes ; Ecosystem ; Adenosine Triphosphatases/metabolism ; Gills/physiology ; Sodium-Potassium-Exchanging ATPase/metabolism ; Salinity
    Chemical Substances Adenosine Triphosphatases (EC 3.6.1.-) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2023-05-16
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1473845-4
    ISSN 1537-5293 ; 1522-2152
    ISSN (online) 1537-5293
    ISSN 1522-2152
    DOI 10.1086/725208
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  3. Article: 3-hydroxykynurenine is a ROS-inducing cytotoxic tryptophan metabolite that disrupts the TCA cycle.

    Buchanan, Jane L / Rauckhorst, Adam J / Taylor, Eric B

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Tryptophan is an essential amino acid that is extensively characterized as a regulator of cellular function through its metabolism by indoleamine 2,3-deoxygenase (IDO) into the kynurenine pathway. However, despite decades of research on tryptophan ... ...

    Abstract Tryptophan is an essential amino acid that is extensively characterized as a regulator of cellular function through its metabolism by indoleamine 2,3-deoxygenase (IDO) into the kynurenine pathway. However, despite decades of research on tryptophan metabolism, the metabolic regulatory roles of it and its metabolites are not well understood. To address this, we performed an activity metabolomics screen of tryptophan and most of its known metabolites in cell culture. We discovered that treatment of human colon cancer cells (HCT116) with 3-hydroxykynurenine (3-HK), a metabolite of kynurenine, potently disrupted TCA cycle function. Citrate and aconitate levels were increased, while isocitrate and all downstream TCA metabolites were decreased, suggesting decreased aconitase function. We hypothesized that 3HK or one of its metabolites increased reactive oxygen species (ROS) and inhibited aconitase activity. Accordingly, we observed almost complete depletion of reduced glutathione and a decrease in total glutathione levels. We observed a dose-dependent decrease in cell viability after 48 hours of 3HK treatment. These data suggest that raising the intracellular levels of 3HK could be sufficient to induce ROS-mediated apoptosis. We modulated the intracellular levels of 3HK by combined induction of IDO and knockdown of kynureninase (KYNU) in HCT116 cells. Cell viability decreased significantly after 48 hours of KYNU knockdown compared to controls, which was accompanied by increased ROS production and Annexin V staining revealing apoptosis. Finally, we identify xanthommatin production from 3-HK as a candidate radical-producing, cytotoxic mechanism. Our work indicates that KYNU may be a target for disrupting tryptophan metabolism. Interestingly, many cancers exhibit overexpression of IDO, providing a cancer-specific metabolic vulnerability that could be exploited by KYNU inhibition.
    Language English
    Publishing date 2023-07-10
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.10.548411
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  4. Article ; Online: A model for stimulation of enzyme activity by a competitive inhibitor based on the interaction of terazosin and phosphoglycerate kinase 1.

    Riley, Mitchell J / Mitchell, Colleen C / Ernst, Sarah E / Taylor, Eric B / Welsh, Michael J

    Proceedings of the National Academy of Sciences of the United States of America

    2024  Volume 121, Issue 9, Page(s) e2318956121

    Abstract: The drug terazosin (TZ) binds to and can enhance the activity of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) and can increase ATP levels. That finding prompted studies of TZ in Parkinson's disease (PD) in which decreased neuronal energy ... ...

    Abstract The drug terazosin (TZ) binds to and can enhance the activity of the glycolytic enzyme phosphoglycerate kinase 1 (PGK1) and can increase ATP levels. That finding prompted studies of TZ in Parkinson's disease (PD) in which decreased neuronal energy metabolism is a hallmark feature. TZ was neuroprotective in cell-based and animal PD models and in large epidemiological studies of humans. However, how TZ might increase PGK1 activity has remained a perplexing question because structural data revealed that the site of TZ binding to PGK1 overlaps with the site of substrate binding, predicting that TZ would competitively inhibit activity. Functional data also indicate that TZ is a competitive inhibitor. To explore the paradoxical observation of a competitive inhibitor increasing enzyme activity under some conditions, we developed a mass action model of TZ and PGK1 interactions using published data on PGK1 kinetics and the effect of varying TZ concentrations. The model indicated that TZ-binding introduces a bypass pathway that accelerates product release. At low concentrations, TZ binding circumvents slow product release and increases the rate of enzymatic phosphotransfer. However, at high concentrations, TZ inhibits PGK1 activity. The model explains stimulation of enzyme activity by a competitive inhibitor and the biphasic dose-response relationship for TZ and PGK1 activity. By providing a plausible mechanism for interactions between TZ and PGK1, these findings may aid development of TZ or other agents as potential therapeutics for neurodegenerative diseases. The results may also have implications for agents that interact with the active site of other enzymes.
    MeSH term(s) Humans ; Animals ; Phosphoglycerate Kinase/metabolism ; Prazosin/pharmacology ; Prazosin/analogs & derivatives ; Parkinson Disease/drug therapy ; Glycolysis
    Chemical Substances Terazosin (8L5014XET7) ; Phosphoglycerate Kinase (EC 2.7.2.3) ; Prazosin (XM03YJ541D)
    Language English
    Publishing date 2024-02-20
    Publishing country United States
    Document type Journal Article
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2318956121
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  5. Article ; Online: Functional Properties of the Mitochondrial Carrier System.

    Taylor, Eric B

    Trends in cell biology

    2017  Volume 27, Issue 9, Page(s) 633–644

    Abstract: The mitochondrial carrier system (MCS) transports small molecules between mitochondria and the cytoplasm. It is integral to the core mitochondrial function to regulate cellular chemistry by metabolism. The mammalian MCS comprises the transporters of the ... ...

    Abstract The mitochondrial carrier system (MCS) transports small molecules between mitochondria and the cytoplasm. It is integral to the core mitochondrial function to regulate cellular chemistry by metabolism. The mammalian MCS comprises the transporters of the 53-member canonical SLC25A family and a lesser number of identified noncanonical transporters. The recent discovery and investigations of the mitochondrial pyruvate carrier (MPC) illustrate the diverse effects a single mitochondrial carrier may exert on cellular function. However, the transport selectivities of many carriers remain unknown, and most have not been functionally investigated in mammalian cells. The mechanisms coordinating their function as a unified system remain undefined. Increased accessibility to molecular genetic and metabolomic technologies now greatly enables investigation of the MCS. Continued investigation of the MCS may reveal how mitochondria encode complex regulatory information within chemical thermodynamic gradients. This understanding may enable precision modulation of cellular chemistry to counteract the dysmetabolism inherent in disease.
    MeSH term(s) Animals ; Biological Transport/physiology ; Humans ; Membrane Transport Proteins/metabolism ; Mitochondria/metabolism ; Mitochondrial Proteins/metabolism
    Chemical Substances Membrane Transport Proteins ; Mitochondrial Proteins ; pyruvate transport protein
    Language English
    Publishing date 2017-05-15
    Publishing country England
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 30122-x
    ISSN 1879-3088 ; 0962-8924
    ISSN (online) 1879-3088
    ISSN 0962-8924
    DOI 10.1016/j.tcb.2017.04.004
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    Zs.MG 25: Show issues
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    Zs.A 3410: Show issues Location:
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  6. Article: Isolated Effects of Plasma Freezing versus Thawing on Metabolite Stability.

    Buchanan, Jane L / Tormes Vaquerano, Jovan / Taylor, Eric B

    Metabolites

    2022  Volume 12, Issue 11

    Abstract: Freezing and thawing plasma samples is known to perturb metabolite stability. However, no study has systematically tested how different freezing and thawing methods affect plasma metabolite levels. The objective of this study was to isolate the effects ... ...

    Abstract Freezing and thawing plasma samples is known to perturb metabolite stability. However, no study has systematically tested how different freezing and thawing methods affect plasma metabolite levels. The objective of this study was to isolate the effects of freezing from thawing on mouse plasma metabolite levels, by comparing a matrix of freezing and thawing conditions through 10 freeze-thaw cycles. We tested freezing with liquid nitrogen (LN
    Language English
    Publishing date 2022-11-11
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2662251-8
    ISSN 2218-1989
    ISSN 2218-1989
    DOI 10.3390/metabo12111098
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  7. Article ; Online: Mitochondrial Pyruvate Carrier Function in Health and Disease across the Lifespan.

    Buchanan, Jane L / Taylor, Eric B

    Biomolecules

    2020  Volume 10, Issue 8

    Abstract: As a nodal mediator of pyruvate metabolism, the mitochondrial pyruvate carrier (MPC) plays a pivotal role in many physiological and pathological processes across the human lifespan, from embryonic development to aging-associated neurodegeneration. ... ...

    Abstract As a nodal mediator of pyruvate metabolism, the mitochondrial pyruvate carrier (MPC) plays a pivotal role in many physiological and pathological processes across the human lifespan, from embryonic development to aging-associated neurodegeneration. Emerging research highlights the importance of the MPC in diverse conditions, such as immune cell activation, cancer cell stemness, and dopamine production in Parkinson's disease models. Whether MPC function ameliorates or contributes to disease is highly specific to tissue and cell type. Cell- and tissue-specific differences in MPC content and activity suggest that MPC function is tightly regulated as a mechanism of metabolic, cellular, and organismal control. Accordingly, recent studies on cancer and diabetes have identified protein-protein interactions, post-translational processes, and transcriptional factors that modulate MPC function. This growing body of literature demonstrates that the MPC and other mitochondrial carriers comprise a versatile and dynamic network undergirding the metabolism of health and disease.
    MeSH term(s) Aging/metabolism ; Animals ; Diabetes Mellitus/metabolism ; Humans ; Mitochondrial Membrane Transport Proteins/genetics ; Mitochondrial Membrane Transport Proteins/metabolism ; Monocarboxylic Acid Transporters/genetics ; Monocarboxylic Acid Transporters/metabolism ; Neoplasms/metabolism ; Neurodegenerative Diseases/metabolism ; Pyruvic Acid/metabolism
    Chemical Substances Mitochondrial Membrane Transport Proteins ; Monocarboxylic Acid Transporters ; Pyruvic Acid (8558G7RUTR)
    Language English
    Publishing date 2020-08-08
    Publishing country Switzerland
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Review
    ZDB-ID 2701262-1
    ISSN 2218-273X ; 2218-273X
    ISSN (online) 2218-273X
    ISSN 2218-273X
    DOI 10.3390/biom10081162
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  8. Article ; Online: Heat Wave Intensity Drives Sublethal Reproductive Costs in a Tidepool Copepod.

    Siegle, Matthew R / Taylor, Eric B / O'Connor, Mary I

    Integrative organismal biology (Oxford, England)

    2022  Volume 4, Issue 1, Page(s) obac005

    Abstract: Physiological stress may induce sublethal effects on fitness by limiting energy availability and shifting energy allocation, which can incur reproductive costs. Sublethal reproductive costs may affect vital rates, linking stress events such as heat waves ...

    Abstract Physiological stress may induce sublethal effects on fitness by limiting energy availability and shifting energy allocation, which can incur reproductive costs. Sublethal reproductive costs may affect vital rates, linking stress events such as heat waves to population demography. Here, we test the hypothesis that heat wave intensity and consecutive days of exposure to heat wave temperatures impact survival and individual reproductive success. We subjected groups of the marine harpacticoid copepod,
    Language English
    Publishing date 2022-01-31
    Publishing country England
    Document type Journal Article
    ISSN 2517-4843
    ISSN (online) 2517-4843
    DOI 10.1093/iob/obac005
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  9. Article ; Online: Freshwater adaptation in prickly sculpin (Pisces: Cottidae): intraspecific comparisons reveal evidence for water pH and Na+ concentration driving diversity in gill H+-ATPase and ion regulation.

    Liu, Shuang / Wilson, Jonathan M / Taylor, Eric B / Richards, Jeffrey G

    The Journal of experimental biology

    2022  Volume 225, Issue 18

    Abstract: Phenotypic divergence is a hallmark of adaptive radiation. One example involves differentiation in physiological traits involved in ion regulation among species with contrasting lifestyles and living in distinct environments. Differentiation in ion ... ...

    Abstract Phenotypic divergence is a hallmark of adaptive radiation. One example involves differentiation in physiological traits involved in ion regulation among species with contrasting lifestyles and living in distinct environments. Differentiation in ion regulation and its ecological implications among populations within species are, however, less well understood. To address this knowledge gap, we collected prickly sculpin (Cottus asper) from distinct habitat types including coastal rivers connected to estuaries, coastal lakes and interior lakes, all from British Columbia, Canada. We tested for differences in plasma Na+ and Cl-, gill Na+/K+-ATPase and H+-ATPase activity and protein abundance as well as changes in body mass and arterial blood pH in fish sampled from the field and acclimated to two different freshwater conditions in the laboratory: artificial lake water (ALW) and ion-poor water (IPW). We also tested for links between environmental water chemistry and the physiological characteristics associated with ion regulation. Transfer to IPW resulted in upregulation of gill Na+/K+-ATPase and H+-ATPase activity as well as increases in gill H+-ATPase protein expression level in each habitat compared with that in the common ALW treatment. Despite the presence of population-within-habitat-type differences, significant habitat-type effects were revealed in most of the ion regulation characteristics examined under different acclimation conditions. Significantly lower plasma Cl- was detected in fish from coastal rivers than in fish from the other two habitat types during the IPW treatment, which was also significantly lower compared with that in ALW. Similarly, gill Na+/K+-ATPase activity was lower in the coastal river populations in IPW than in fish from coastal and interior lakes, which was not in accordance with the protein expression in the gill. For gill H+-ATPase, fish from interior lake populations had the highest level of activity across all habitat types under all conditions, which was related to the protein levels in the gill. The activity of gill H+-ATPase was positively correlated with the combined effect of water Na+ and pH under the ALW treatment. Our results suggest that variation in habitat may be an important factor driving differences in gill Na+/K+-ATPase and H+-ATPase activity across populations of C. asper. Further, the combined effect of water Na+ and pH may have played a key role in physiological adaptation in C. asper during post-glacial freshwater colonization and dispersal.
    MeSH term(s) Acclimatization/physiology ; Adaptation, Physiological ; Animals ; Fishes/metabolism ; Fresh Water ; Gills/metabolism ; Hydrogen-Ion Concentration ; Ions/metabolism ; Perciformes/metabolism ; Proton-Translocating ATPases/metabolism ; Seawater ; Sodium/metabolism ; Sodium-Potassium-Exchanging ATPase/metabolism ; Water/metabolism
    Chemical Substances Ions ; Water (059QF0KO0R) ; Sodium (9NEZ333N27) ; Proton-Translocating ATPases (EC 3.6.3.14) ; Sodium-Potassium-Exchanging ATPase (EC 7.2.2.13)
    Language English
    Publishing date 2022-09-22
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 218085-6
    ISSN 1477-9145 ; 0022-0949
    ISSN (online) 1477-9145
    ISSN 0022-0949
    DOI 10.1242/jeb.243500
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    Zs.A 2629: Show issues Location:
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  10. Article ; Online: Glycerol monolaurate inhibits

    Upton, Ellen M / Schlievert, Patrick M / Zhang, Yifeng / Rauckhorst, Adam J / Taylor, Eric B / Radoshevich, Lilliana

    microPublication biology

    2023  Volume 2023

    Abstract: Glycerol Monolaurate (GML) is a naturally occurring fatty acid monoester with antimicrobial properties. ...

    Abstract Glycerol Monolaurate (GML) is a naturally occurring fatty acid monoester with antimicrobial properties.
    Language English
    Publishing date 2023-10-27
    Publishing country United States
    Document type Journal Article
    ISSN 2578-9430
    ISSN (online) 2578-9430
    DOI 10.17912/micropub.biology.000905
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