Rac and p38 kinase mediate 5-lipoxygenase translocation and cell death

Young Woo Eom, Sung Hoon Cho, Jung Sun Hwang, Suk Bum Yoon, Doe Sun Na, Il Jun Kang, Sang Sun Kang, Woo Keun Song, Jae-Hong Kim

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

5-Lipoxygenase (5-LO) is a key enzyme involved in the synthesis of leukotrienes from arachidonic acid, and its activation is usually followed by translocation to the nuclear envelope. The details of mechanisms involved in the translocation of 5-LO are not well understood, though Ca 2+ is known to be essential. Here we show that ionomycin, a Ca 2+ ionophore, induces 5-LO translocation and necrotic cell death in Rat-2 fibroblasts, suggesting a potential relationship between activation of 5-LO and cell death. These effects were markedly attenuated in Rat2-Rac N17 cells expressing a dominant negative Rac1 mutant. Pretreatment with SB203580, a specific inhibitor of p38 MAP kinase, or EGTA, a Ca 2+ chelator, likewise diminished ionomycin-induced 5-LO translocation and cell death, but PD98059, a MEK inhibitor, did not. Thus, Rac and p38 MAP kinase appear to be components in a Ca 2+-dependent pathway leading to 5-LO translocation and necrotic cell death in Rat-2 fibroblasts.

Original languageEnglish
Pages (from-to)126-132
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume284
Issue number1
DOIs
Publication statusPublished - 2001 Oct 14
Externally publishedYes

Keywords

  • 5-lipoxygenase
  • Ionomycin
  • Necrosis
  • p38 MAP kinase
  • Rac

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

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  • Cite this

    Eom, Y. W., Cho, S. H., Hwang, J. S., Yoon, S. B., Na, D. S., Kang, I. J., Kang, S. S., Song, W. K., & Kim, J-H. (2001). Rac and p38 kinase mediate 5-lipoxygenase translocation and cell death. Biochemical and Biophysical Research Communications, 284(1), 126-132. https://doi.org/10.1006/bbrc.2001.4937