Participation of MAP kinase p38 and IκB kinase in chromium (VI)-induced NF-κB and AP-1 activation

F. Chen, M. Ding, Y. Lu, S. S. Leonard, V. Vallyathan, V. Castranova, X. Shi

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Epidemiological studies demonstrate that environmental and occupational exposure of chromium(VI) [Cr(VI)] or Cr(VI)-containing particles can cause a number of human diseases, including inflammation and cancer. The biological mechanisms responsible for the initiation and progression of diseases resulting from exposure to Cr(VI) are not fully understood. The present studies evaluated the ability of Cr(IV) to induce activation of NF-κB and AP-1, two important transcription factors governing the expression of many early response genes involved in inflammation and carcinogenesis. The activation of NF-κB and AP-1 by Cr(IV) was dose dependent. Aspirin, a well-established antioxidant, substantially inhibited Cr(VI)-induced activation of both NF-κB and AP-1. SB202190, a specific inhibitor for p38, attenuated AP-1 activation induced by Cr(IV), whereas PD98059, a specific inhibitor for Erk, exhibited no effect on Cr(IV)-induced AP-1 activation. Blockage of NF-κB signaling pathway by a transient transfection of a dominant negative expressing vector for IκB kinase β resulted in inhibition of Cr(IV)-induced NF-κB, but not AP-1 activation. These data suggest that the activation of AP-1 or NF-κB by Cr(IV) is through the involvement of MAP kinase or IKK pathway, respectively.

Original languageEnglish
Pages (from-to)231-238
Number of pages8
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume19
Issue number3
StatePublished - 2000

Keywords

  • AP-1
  • Cr(VI)
  • MAP kinase
  • NF-κB

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Toxicology
  • Health, Toxicology and Mutagenesis

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