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Activation of 2-Aminofluorene by Prostaglandin Endoperoxide H Synthase 2

Liu, Y ; Levy, G.N ; Weber, W.W

Biochemical and Biophysical Research Communications, 04 October 1995, Vol.215(1), pp.346-354 [Periódico revisado por pares]

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  • Título:
    Activation of 2-Aminofluorene by Prostaglandin Endoperoxide H Synthase 2
  • Autor: Liu, Y ; Levy, G.N ; Weber, W.W
  • Assuntos: Biology ; Chemistry ; Anatomy & Physiology
  • É parte de: Biochemical and Biophysical Research Communications, 04 October 1995, Vol.215(1), pp.346-354
  • Descrição: Prostaglandin endoperoxide H synthase is the key enzyme in the conversion of arachidonic acid to tissue prostanoids. Two isoforms of prostaglandin endoperoxide H synthase have been identified: PHS-1 is constitutively expressed in most tissues under normal physiological conditions and PHS-2 is expressed in response to inflammatory agents, tumor promotors, and other agents related to mitogenesis. Previous work demonstrated that PHS-1 can activate arylamine carcinogens. We report here that PHS-2 can also activate an arylamine carcinogen to form DNA adducts. This is shown by: (1) use of purified ovine PHS-2 to form DNA adducts; (2) increased DNA adduct formation, PHS-2 mRNA, and PHS-2 protein after treatment of HUVEC cells with the PHS-2 inducer PMA; and (3) transient expression of PHS-2 cDNA in COS-1 cells gave rise to both elevations of PHS-2 enzyme protein and DNA adduct formation. Finally, two PHS inhibitors, aspirin and indomethacin, showed significant inhibition of PHS-2-mediated DNA...
  • Idioma: Inglês

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