Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

Jenny Worthington, T Robson, M Murray, M O'Rourke, G Keilty, DG Hirst

    Research output: Contribution to journalArticle

    50 Citations (Scopus)

    Abstract

    It may be therapeutically advantageous to alter tumour blood supply specifically. Nitric oxide is a potent vasodilator which is produced in many tissues by the enzyme nitric oxide synthase (NOS). We have transfected cDNA for the inducible isoform of this enzyme (iNOS), under the control of the radiation-inducible promoter WAF1. The activity of the promoter was initially assessed using green fluorescent protein (GFP) in both endothelial cells and rat tail artery segments, Induction of protein expression by 9.5- and 4.5-fold respectively, was observed after a radiation dose of 4 Gy. Artery sections were then transfected with the WAF1/iNOS construct; this gave five-fold induction of iNOS protein after a dose of 4 Gy. The transfected artery was also tested functionally for relaxation, indicative of NO production. One hour after exposure to 4 Gy there was a significant (65%) relaxation of artery segments that had been preconstricted with phenylephrine. This could be partially reversed by the NOS inhibitor nitro-L-arginine. This study demonstrates that we can regulate vascular tone using an X-ray inducible promoter.
    LanguageEnglish
    Pages1126-1131
    JournalGene Therapy
    Volume7
    Issue number13
    Publication statusPublished - Jul 2000

    Fingerprint

    Blood Vessels
    Arteries
    Radiation
    Nitric Oxide Synthase
    Phenylephrine
    Enzymes
    Green Fluorescent Proteins
    Vasodilator Agents
    Arginine
    Tail
    Nitric Oxide
    Protein Isoforms
    Proteins
    Endothelial Cells
    Complementary DNA
    X-Rays
    Neoplasms

    Cite this

    Worthington, J., Robson, T., Murray, M., O'Rourke, M., Keilty, G., & Hirst, DG. (2000). Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. Gene Therapy, 7(13), 1126-1131.
    Worthington, Jenny ; Robson, T ; Murray, M ; O'Rourke, M ; Keilty, G ; Hirst, DG. / Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. In: Gene Therapy. 2000 ; Vol. 7, No. 13. pp. 1126-1131.
    @article{b00a5707bdd24dceae9e52aa0eb32138,
    title = "Modification of vascular tone using iNOS under the control of a radiation-inducible promoter",
    abstract = "It may be therapeutically advantageous to alter tumour blood supply specifically. Nitric oxide is a potent vasodilator which is produced in many tissues by the enzyme nitric oxide synthase (NOS). We have transfected cDNA for the inducible isoform of this enzyme (iNOS), under the control of the radiation-inducible promoter WAF1. The activity of the promoter was initially assessed using green fluorescent protein (GFP) in both endothelial cells and rat tail artery segments, Induction of protein expression by 9.5- and 4.5-fold respectively, was observed after a radiation dose of 4 Gy. Artery sections were then transfected with the WAF1/iNOS construct; this gave five-fold induction of iNOS protein after a dose of 4 Gy. The transfected artery was also tested functionally for relaxation, indicative of NO production. One hour after exposure to 4 Gy there was a significant (65{\%}) relaxation of artery segments that had been preconstricted with phenylephrine. This could be partially reversed by the NOS inhibitor nitro-L-arginine. This study demonstrates that we can regulate vascular tone using an X-ray inducible promoter.",
    author = "Jenny Worthington and T Robson and M Murray and M O'Rourke and G Keilty and DG Hirst",
    year = "2000",
    month = "7",
    language = "English",
    volume = "7",
    pages = "1126--1131",
    journal = "Gene Therapy",
    issn = "0969-7128",
    number = "13",

    }

    Worthington, J, Robson, T, Murray, M, O'Rourke, M, Keilty, G & Hirst, DG 2000, 'Modification of vascular tone using iNOS under the control of a radiation-inducible promoter', Gene Therapy, vol. 7, no. 13, pp. 1126-1131.

    Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. / Worthington, Jenny; Robson, T; Murray, M; O'Rourke, M; Keilty, G; Hirst, DG.

    In: Gene Therapy, Vol. 7, No. 13, 07.2000, p. 1126-1131.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Modification of vascular tone using iNOS under the control of a radiation-inducible promoter

    AU - Worthington, Jenny

    AU - Robson, T

    AU - Murray, M

    AU - O'Rourke, M

    AU - Keilty, G

    AU - Hirst, DG

    PY - 2000/7

    Y1 - 2000/7

    N2 - It may be therapeutically advantageous to alter tumour blood supply specifically. Nitric oxide is a potent vasodilator which is produced in many tissues by the enzyme nitric oxide synthase (NOS). We have transfected cDNA for the inducible isoform of this enzyme (iNOS), under the control of the radiation-inducible promoter WAF1. The activity of the promoter was initially assessed using green fluorescent protein (GFP) in both endothelial cells and rat tail artery segments, Induction of protein expression by 9.5- and 4.5-fold respectively, was observed after a radiation dose of 4 Gy. Artery sections were then transfected with the WAF1/iNOS construct; this gave five-fold induction of iNOS protein after a dose of 4 Gy. The transfected artery was also tested functionally for relaxation, indicative of NO production. One hour after exposure to 4 Gy there was a significant (65%) relaxation of artery segments that had been preconstricted with phenylephrine. This could be partially reversed by the NOS inhibitor nitro-L-arginine. This study demonstrates that we can regulate vascular tone using an X-ray inducible promoter.

    AB - It may be therapeutically advantageous to alter tumour blood supply specifically. Nitric oxide is a potent vasodilator which is produced in many tissues by the enzyme nitric oxide synthase (NOS). We have transfected cDNA for the inducible isoform of this enzyme (iNOS), under the control of the radiation-inducible promoter WAF1. The activity of the promoter was initially assessed using green fluorescent protein (GFP) in both endothelial cells and rat tail artery segments, Induction of protein expression by 9.5- and 4.5-fold respectively, was observed after a radiation dose of 4 Gy. Artery sections were then transfected with the WAF1/iNOS construct; this gave five-fold induction of iNOS protein after a dose of 4 Gy. The transfected artery was also tested functionally for relaxation, indicative of NO production. One hour after exposure to 4 Gy there was a significant (65%) relaxation of artery segments that had been preconstricted with phenylephrine. This could be partially reversed by the NOS inhibitor nitro-L-arginine. This study demonstrates that we can regulate vascular tone using an X-ray inducible promoter.

    M3 - Article

    VL - 7

    SP - 1126

    EP - 1131

    JO - Gene Therapy

    T2 - Gene Therapy

    JF - Gene Therapy

    SN - 0969-7128

    IS - 13

    ER -

    Worthington J, Robson T, Murray M, O'Rourke M, Keilty G, Hirst DG. Modification of vascular tone using iNOS under the control of a radiation-inducible promoter. Gene Therapy. 2000 Jul;7(13):1126-1131.