Sildenafil protects human mammary epithelial cells against ROS production induced by estradiol

Cocciadiferro, L; Miceli, V; Carruba, G; Nicotra, C.M.A.

    Research output: Contribution to journalArticle

    Abstract

    Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form (XO) play an important role in various types of ischemic and vascular injuries. Recently, we have demonstrated that estradiol (E2) induces a significant decrease of the expression and activity of XDH and of its conversion to XO in human mammary epithelial cells. E2 is known to induce upregulation of eNOS gene expression in aortic endothelial cells. Because the XO-derived O2•– combines with •NO to yield ONOO–, and considering that ONOO– converts XDH to XO, the resulting increase of XO activity and reactive oxygen species production would eventually lead to a further increase of ONOO– production, thus creating a vicious cycle of oxidative stress. Our previous study has indicated that sildenafil has a protective effect on human mammary epithelial cells as a consequence of XO inhibition and of the resulting decrease of free oxygen radicals that can impair the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the present study, we report that the dual inhibitory effect exerted by sildenafil on both XO and PDE-5 is a consequence of a structural modification induced by O2•–, also consisting of the release of a piperazine group that could in turn inhibit the XO enzyme.
    Original languageEnglish
    Pages (from-to)255-258
    Number of pages4
    JournalHormone Molecular Biology and Clinical Investigation
    Volume6(3)
    Publication statusPublished - 2011

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    Xanthine Dehydrogenase
    Estradiol
    Breast
    Epithelial Cells
    Reactive Oxygen Species
    Type 5 Cyclic Nucleotide Phosphodiesterases
    NADPH Oxidase
    Vascular System Injuries
    Free Radicals
    Oxidoreductases
    Oxidative Stress
    Up-Regulation
    Endothelial Cells
    Gene Expression
    Enzymes
    Sildenafil Citrate

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    Sildenafil protects human mammary epithelial cells against ROS production induced by estradiol. / Cocciadiferro, L; Miceli, V; Carruba, G; Nicotra, C.M.A.

    In: Hormone Molecular Biology and Clinical Investigation, Vol. 6(3), 2011, p. 255-258.

    Research output: Contribution to journalArticle

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    abstract = "Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form (XO) play an important role in various types of ischemic and vascular injuries. Recently, we have demonstrated that estradiol (E2) induces a significant decrease of the expression and activity of XDH and of its conversion to XO in human mammary epithelial cells. E2 is known to induce upregulation of eNOS gene expression in aortic endothelial cells. Because the XO-derived O2•– combines with •NO to yield ONOO–, and considering that ONOO– converts XDH to XO, the resulting increase of XO activity and reactive oxygen species production would eventually lead to a further increase of ONOO– production, thus creating a vicious cycle of oxidative stress. Our previous study has indicated that sildenafil has a protective effect on human mammary epithelial cells as a consequence of XO inhibition and of the resulting decrease of free oxygen radicals that can impair the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the present study, we report that the dual inhibitory effect exerted by sildenafil on both XO and PDE-5 is a consequence of a structural modification induced by O2•–, also consisting of the release of a piperazine group that could in turn inhibit the XO enzyme.",
    keywords = "estradiol (E2), human mammaty epithelial cells (HMECs), oxidative stress inhibition, reactive oxygen species (ROS) production, sildenafil, xanthine dehydrogenase (XDH), xanthine oxidase (XO).",
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    AU - Cocciadiferro, L; Miceli, V; Carruba, G; Nicotra, C.M.A.

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    N2 - Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form (XO) play an important role in various types of ischemic and vascular injuries. Recently, we have demonstrated that estradiol (E2) induces a significant decrease of the expression and activity of XDH and of its conversion to XO in human mammary epithelial cells. E2 is known to induce upregulation of eNOS gene expression in aortic endothelial cells. Because the XO-derived O2•– combines with •NO to yield ONOO–, and considering that ONOO– converts XDH to XO, the resulting increase of XO activity and reactive oxygen species production would eventually lead to a further increase of ONOO– production, thus creating a vicious cycle of oxidative stress. Our previous study has indicated that sildenafil has a protective effect on human mammary epithelial cells as a consequence of XO inhibition and of the resulting decrease of free oxygen radicals that can impair the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the present study, we report that the dual inhibitory effect exerted by sildenafil on both XO and PDE-5 is a consequence of a structural modification induced by O2•–, also consisting of the release of a piperazine group that could in turn inhibit the XO enzyme.

    AB - Several studies suggest that xanthine dehydrogenase (XDH) and its oxidase form (XO) play an important role in various types of ischemic and vascular injuries. Recently, we have demonstrated that estradiol (E2) induces a significant decrease of the expression and activity of XDH and of its conversion to XO in human mammary epithelial cells. E2 is known to induce upregulation of eNOS gene expression in aortic endothelial cells. Because the XO-derived O2•– combines with •NO to yield ONOO–, and considering that ONOO– converts XDH to XO, the resulting increase of XO activity and reactive oxygen species production would eventually lead to a further increase of ONOO– production, thus creating a vicious cycle of oxidative stress. Our previous study has indicated that sildenafil has a protective effect on human mammary epithelial cells as a consequence of XO inhibition and of the resulting decrease of free oxygen radicals that can impair the expression of NADPH oxidase and type 5 phosphodiesterase (PDE-5). In the present study, we report that the dual inhibitory effect exerted by sildenafil on both XO and PDE-5 is a consequence of a structural modification induced by O2•–, also consisting of the release of a piperazine group that could in turn inhibit the XO enzyme.

    KW - estradiol (E2), human mammaty epithelial cells (HMECs), oxidative stress inhibition, reactive oxygen species (ROS) production, sildenafil, xanthine dehydrogenase (XDH), xanthine oxidase (XO).

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