Activation of PKC is required for arsenite-induced signal transduction

N. Y. Chen, Wei-Ya Ma, C. Huang, M. Ding, Zigang Dong

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

Trivalent arsenic (arsenite) is a human carcinogen. However, the molecular mechanism of arsenite-induced carcinogenesis is still not well understood. In this study, we found that arsenite induced translocation of PKCε, PKCδ, and PKCα from cytosol to membranes. Rottlerin, a selective inhibitor for PKCδ, and safingol, a specific inhibitor for PKCα, both markedly inhibited arsenite-induced AP-1 activity. These inhibitory effects by rottlerin and safingol appeared to be dose dependent. Arsenite-induced phosphorylation of Erks was inhibited by rottlerin, while safingol inhibited arsenite-induced phosphorylation of JNKs and p38 kinases. Dominant negative mutant transfectant of PKCε markedly blocked arsenite-induced AP-1 activity and the phosphorylation of Erks, JNKs, and p38 kinases. These data demonstrate that PKCδ, PKCε, and PKCα mediate arsenite-induced AP-1 activation in JB6 cells through different MAP kinase (Erks, JNKs, and p38 kinases) pathways.

Original languageEnglish (US)
Pages (from-to)297-305
Number of pages9
JournalJournal of Environmental Pathology, Toxicology and Oncology
Volume19
Issue number3
StatePublished - 2000

Keywords

  • AP-1
  • Arsenite
  • MAP kinase
  • PKC

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