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Protection of human keratinocyte mtDNA by low-level nitric oxide

  1. Author:
    Shokolenko, I.
    Oberyszyn, T. M.
    D'Ambrosio, S. M.
    Saavedra, J. E.
    Keefer, L. K.
    LeDoux, S. P.
    Wilson, G. L.
    Robertson, F. M.

  2. Author Address

    Ohio State Univ, Dept Mol Virol Immunol & Med Genet, 2184 Graves Hall, 333 W 10th Ave, Columbus, OH 43210 USA. Ohio State Univ, Dept Mol Virol Immunol & Med Genet, Columbus, OH 43210 USA. Univ S Alabama, Coll Med, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA. Ohio State Univ, Coll Med, Dept Radiol, Div Radiobiol, Columbus, OH 43210 USA. NCI, Frederick Canc Res & Dev Ctr, SAIC Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Robertson FM Ohio State Univ, Dept Mol Virol Immunol & Med Genet, 2184 Graves Hall, 333 W 10th Ave, Columbus, OH 43210 USA.
    1. Year: 2002
  2. Journal: Nitric Oxide-Biology and Chemistry
    1. 5
    2. 6
    3. Pages: 555-560
  4. Type of Article: Article
  1. Abstract:

    This study was designed to evaluate the DNA damaging effects of nitric oxide and to determine whether the endogenous generation of nitric oxide at low levels in the cell exerts a protective effect against this damage. Damage to mitochondrial and nuclear DNA in normal human epidermal keratinocytes (NHEK) was assessed after treatment of these cells with varying concentrations of S-nitroso-N-acetylpenicillamine, which decomposes to release nitric oxide. The results showed that mitochondrial DNA was more vulnerable to nitric oxide-induced damage than was a similarly sized fragment of the beta -globin gene. To evaluate the effects on DNA damage by pretreatment of cells with low- levels of nitric oxide, NHEK cells were treated with the prodrug V-PYRRO/NO. This agent is metabolized inside these cells and releases small quantities of nitric oxide. The cells then were exposed to damaging amounts of nitric oxide produced by S-nitroso-N-acetylpenicillamine. The results of these studies showed that pretreatment of NHEK cells with V-PYRRO/NO attenuated the mtDNA damage and loss of cell viability produced by exposure to S-nitroso-N-acetylpenicillamine. (C) 2001 Elsevier Science.

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