The role of hydroxyl radical as a messenger in Cr(VI)-induced p53 activation

Suwei Wang, Stephen S. Leonard, Jianping Ye, Min Ding, Xianglin Shi

Research output: Contribution to journalArticlepeer-review

103 Scopus citations

Abstract

The present study investigates whether reactive oxygen species (ROS) are involved in p53 activation, and if they are, which species is responsible for the activation. Our hypothesis is that hydroxyl radical (·OH) functions as a messenger for the activation of this tumor suppressor protein. Human lung epithelial cells (A549) were used to test this hypothesis. Cr(VI) was employed as the source of ROS due to its ability to generate a whole spectrum of ROS inside the cell. Cr(VI) is able to activate p53 by increasing the protein levels and enhancing both the DNA binding activity and transactivation ability of the protein. Increased cellular levels ofsuperoxide radicals (O2/-·), hydrogen peroxide (H2O2), and ·OH radicals were detected on the addition of Cr(VI) to the cells. Superoxide dismutase, by enhancing the production of H2O2 from O2/-· radicals, increased p53 activity. Catalase, an H2O2 scavenger, eliminated ·OH radical generation and inhibited p53 activation. Sodium formate and aspirin, ·OH radical scavengers, also suppressed p53 activation. Deferoxamine, a metal chelator, inhibited p53 activation by chelating Cr(V) to make it incapable of generating radicals from H2O2. NADPH, which accelerated the one-electron reduction of Cr(VI) to Cr(V) and increased ·OH radical generation, dramatically enhanced p53 activation. Thus ·OH radical generated from Cr(VI) reduction in A549 cells is responsible for Cr(VI)-induced p53 activation.

Original languageEnglish
Pages (from-to)C868-C875
JournalAmerican Journal of Physiology - Cell Physiology
Volume279
Issue number3 48-3
DOIs
StatePublished - 2000

Keywords

  • Cr(VI) carcinogenesis
  • Reactive oxygen species

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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