Pyridine Alkaloid

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Junichi Kobayashi - One of the best experts on this subject based on the ideXlab platform.

Suvi T. Häkkinen - One of the best experts on this subject based on the ideXlab platform.

  • erratum to functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco phytochemistry 68 2007 2773 2785
    Phytochemistry, 2008
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Agnieszka Šwiątek, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Kirsimarja Oksmancaldentey
    Abstract:

    VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Espoo), Finland VIB Department of Plant Systems Biology, Technologiepark 927, B-9052 Gent, Belgium Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Gent, Belgium d Laboratory of Plant Biochemistry and Physiology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

  • Erratum to “Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco” [Phytochemistry 68 (2007) 2773–2785]
    Phytochemistry, 2008
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Agnieszka Šwiątek, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Kirsi-marja Oksman-caldentey
    Abstract:

    VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Espoo), Finland VIB Department of Plant Systems Biology, Technologiepark 927, B-9052 Gent, Belgium Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Gent, Belgium d Laboratory of Plant Biochemistry and Physiology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

  • Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco.
    Phytochemistry, 2007
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Agnieszka Swiatek, Kirsi-marja Oksman-caldentey
    Abstract:

    Although secondary metabolism in Nicotiana tabacum (L.) (tobacco) is rather well studied, many molecular aspects of the biosynthetic pathways and their regulation remain to be disclosed, even for prominent compounds such as nicotine and other Pyridine Alkaloids. To identify players in tobacco Pyridine Alkaloid biosynthesis a functional screen was performed, starting from a tobacco gene collection established previously by means of combined transcript profiling and metabolite analysis. First, full-length cDNA clones were isolated for 34 genes, corresponding to tobacco transcript tag sequences putatively associated with Pyridine Alkaloid metabolism. Full-length open reading frames were transferred to pCaMV35S-steered overexpression vectors. The effects of plant transformation with these expression cassettes on the accumulation of nicotine and other Pyridine Alkaloids were assessed in transgenic tobacco Bright-Yellow 2 (BY-2) cell suspensions and hairy root cultures. This screen identified potential catalysers of tobacco Pyridine metabolism, amongst which a lysine decarboxylase-like gene and a GH3-like enzyme. Overexpression of the GH3-like enzyme, presumably involved in auxin homeostasis and designated NtNEG1 (Nicotiana tabacum Nicotine-Enhancing GH3 enzyme 1), increased nicotine levels in BY-2 hairy roots significantly. This study shows how functional genomics-based identification of genes potentially involved in biosynthetic pathways followed by systematic functional assays in plant cells can be used at large-scale to decipher plant metabolic networks at the molecular level.

Kirsi-marja Oksman-caldentey - One of the best experts on this subject based on the ideXlab platform.

  • Erratum to “Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco” [Phytochemistry 68 (2007) 2773–2785]
    Phytochemistry, 2008
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Agnieszka Šwiątek, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Kirsi-marja Oksman-caldentey
    Abstract:

    VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Espoo), Finland VIB Department of Plant Systems Biology, Technologiepark 927, B-9052 Gent, Belgium Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Gent, Belgium d Laboratory of Plant Biochemistry and Physiology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

  • Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco.
    Phytochemistry, 2007
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Agnieszka Swiatek, Kirsi-marja Oksman-caldentey
    Abstract:

    Although secondary metabolism in Nicotiana tabacum (L.) (tobacco) is rather well studied, many molecular aspects of the biosynthetic pathways and their regulation remain to be disclosed, even for prominent compounds such as nicotine and other Pyridine Alkaloids. To identify players in tobacco Pyridine Alkaloid biosynthesis a functional screen was performed, starting from a tobacco gene collection established previously by means of combined transcript profiling and metabolite analysis. First, full-length cDNA clones were isolated for 34 genes, corresponding to tobacco transcript tag sequences putatively associated with Pyridine Alkaloid metabolism. Full-length open reading frames were transferred to pCaMV35S-steered overexpression vectors. The effects of plant transformation with these expression cassettes on the accumulation of nicotine and other Pyridine Alkaloids were assessed in transgenic tobacco Bright-Yellow 2 (BY-2) cell suspensions and hairy root cultures. This screen identified potential catalysers of tobacco Pyridine metabolism, amongst which a lysine decarboxylase-like gene and a GH3-like enzyme. Overexpression of the GH3-like enzyme, presumably involved in auxin homeostasis and designated NtNEG1 (Nicotiana tabacum Nicotine-Enhancing GH3 enzyme 1), increased nicotine levels in BY-2 hairy roots significantly. This study shows how functional genomics-based identification of genes potentially involved in biosynthetic pathways followed by systematic functional assays in plant cells can be used at large-scale to decipher plant metabolic networks at the molecular level.

Kip E. Panter - One of the best experts on this subject based on the ideXlab platform.

  • piperidine Pyridine Alkaloid inhibition of fetal movement in a day 40 pregnant goat model
    Food and Chemical Toxicology, 2013
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Kip E. Panter
    Abstract:

    Abstract Inhibition of fetal movement is one mechanism behind the development of multiple congenital contracture-type defects in developing fetuses of humans and animals. We tested the Alkaloids anabasine, lobeline, and myosmine for agonist actions, and sensitivity to alpha conotoxins EI and GI blockade at fetal muscle-type nicotinic acetylcholine receptors (nAChR) expressed by TE-671 cells. We also determined if the Alkaloids decreased fetal movement in an IV dosed, day 40 pregnant goat model. In TE-671 cells, all three Alkaloids elicited concentration-dependent changes in membrane potential sensing dye fluorescence. 1.0 μM alpha conotoxin GI shifted the concentration–effect curves of anabasine and myosmine to the right, and decreased maximal responses. Neither of the conotoxins blocked the actions of lobeline in TE-671 cells. In the day 40 pregnant goats, 0.8 mg/kg anabasine abolished fetal movement at 30 and 60 min after dosing and fetal movement was reduced by lobeline and myosmine. The blockade of anabasine and myosmine actions in TE-671 cells by alpha conotoxin GI indicates that they are agonists at fetal muscle-type nAChR. All three Alkaloids did significantly decrease fetal movement in the day 40 pregnant goat model suggesting a potential for these Alkaloids to cause multiple congenital contracture-type defects in developing fetuses.

  • fetal muscle type nicotinic acetylcholine receptor activation in te 671 cells and inhibition of fetal movement in a day 40 pregnant goat model by optical isomers of the piperidine Alkaloid coniine
    Journal of Pharmacology and Experimental Therapeutics, 2013
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Kip E. Panter
    Abstract:

    Coniine is an optically active toxic piperidine Alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock ( Conium maculatum L. ). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged desensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (−)-coniine, (+)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, α-conotoxins (CTx) EI and GI were used to antagonize the actions of (+)- and (−)-coniine in TE-671 cells. (−)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (+)-coniine, suggesting stereoselectivity by the receptor. The Pyridine Alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demonstrating concentration-dependent coagonism and selective antagonism. These results provide pharmacological evidence that the piperidine Alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner.

  • Pregnant Goat Model by Optical Isomers of the Piperidine Alkaloid Coniine
    2012
    Co-Authors: Benedict T Green, Kevin D Welch, James A Pfister, Stephen T. Lee, Kip E. Panter
    Abstract:

    Coniine is an optically active toxic piperidine Alkaloid and nicotinic acetylcholine receptor (nAChR) agonist found in poison hemlock (Conium maculatum L.). Coniine teratogenicity is hypothesized to be attributable to the binding, activation, and prolonged de-sensitization of fetal muscle-type nAChR, which results in the complete inhibition of fetal movement. However, pharmacological evidence of coniine actions at fetal muscle-type nAChR is lacking. The present study compared (2)-coniine, (1)-coniine, and nicotine for the ability to inhibit fetal movement in a day 40 pregnant goat model and in TE-671 cells that express fetal muscle-type nAChR. Furthermore, a-conotoxins (CTx) EI and GI were used to antagonize the actions of (1)- and (2)-coniine in TE-671 cells. (2)-Coniine was more effective at eliciting electrical changes in TE-671 cells and inhibiting fetal movement than was (1)-coniine, suggesting stereoselectivity by the receptor. The Pyridine Alkaloid nicotine did not inhibit fetal movement in a day 40 pregnant goat model, suggesting agonist specificity for the inhibition of fetal movement. Low concentrations of both CTxs potentiated the TE-671 cell response and higher concentrations of CTx EI, and GI antagonized the actions of both coniine enantiomers demon-strating concentration-dependent coagonism and selective an-tagonism. These results provide pharmacological evidence that the piperidine Alkaloid coniine is acting at fetal muscle-type nAChR in a concentration-dependent manner

Dirk Inzé - One of the best experts on this subject based on the ideXlab platform.

  • erratum to functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco phytochemistry 68 2007 2773 2785
    Phytochemistry, 2008
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Agnieszka Šwiątek, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Kirsimarja Oksmancaldentey
    Abstract:

    VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Espoo), Finland VIB Department of Plant Systems Biology, Technologiepark 927, B-9052 Gent, Belgium Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Gent, Belgium d Laboratory of Plant Biochemistry and Physiology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

  • Erratum to “Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco” [Phytochemistry 68 (2007) 2773–2785]
    Phytochemistry, 2008
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Agnieszka Šwiątek, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Kirsi-marja Oksman-caldentey
    Abstract:

    VTT Technical Research Centre of Finland, P.O. Box 1000, FIN-02044 VTT (Espoo), Finland VIB Department of Plant Systems Biology, Technologiepark 927, B-9052 Gent, Belgium Department of Molecular Genetics, Ghent University, Technologiepark 927, B-9052 Gent, Belgium d Laboratory of Plant Biochemistry and Physiology, Department of Biology, University of Antwerp, Groenenborgerlaan 171, B-2020 Antwerp, Belgium

  • Functional characterisation of genes involved in Pyridine Alkaloid biosynthesis in tobacco.
    Phytochemistry, 2007
    Co-Authors: Suvi T. Häkkinen, Sofie Tilleman, Valerie De Sutter, Heiko Rischer, Isabelle Vanhoutte, Harry Van Onckelen, Pierre Hilson, Dirk Inzé, Agnieszka Swiatek, Kirsi-marja Oksman-caldentey
    Abstract:

    Although secondary metabolism in Nicotiana tabacum (L.) (tobacco) is rather well studied, many molecular aspects of the biosynthetic pathways and their regulation remain to be disclosed, even for prominent compounds such as nicotine and other Pyridine Alkaloids. To identify players in tobacco Pyridine Alkaloid biosynthesis a functional screen was performed, starting from a tobacco gene collection established previously by means of combined transcript profiling and metabolite analysis. First, full-length cDNA clones were isolated for 34 genes, corresponding to tobacco transcript tag sequences putatively associated with Pyridine Alkaloid metabolism. Full-length open reading frames were transferred to pCaMV35S-steered overexpression vectors. The effects of plant transformation with these expression cassettes on the accumulation of nicotine and other Pyridine Alkaloids were assessed in transgenic tobacco Bright-Yellow 2 (BY-2) cell suspensions and hairy root cultures. This screen identified potential catalysers of tobacco Pyridine metabolism, amongst which a lysine decarboxylase-like gene and a GH3-like enzyme. Overexpression of the GH3-like enzyme, presumably involved in auxin homeostasis and designated NtNEG1 (Nicotiana tabacum Nicotine-Enhancing GH3 enzyme 1), increased nicotine levels in BY-2 hairy roots significantly. This study shows how functional genomics-based identification of genes potentially involved in biosynthetic pathways followed by systematic functional assays in plant cells can be used at large-scale to decipher plant metabolic networks at the molecular level.