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 journalArticlepeer-review

13 Citations (Scopus)


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 Ca2+ is known to be essential. Here we show that ionomycin, a Ca2+ 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-RacN17 cells expressing a dominant negative Rac1 mutant. Pretreatment with SB203580, a specific inhibitor of p38 MAP kinase, or EGTA, a Ca2+ 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 Ca2+-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
Issue number1
Publication statusPublished - 2001
Externally publishedYes

Bibliographical note

Funding Information:
We thank Dr. Abramovitz (Canada Merck, Canada) for the human 5-LO cDNA. This work was supported by grants from the National Research Laboratory (NRL), Molecular Medical Science Research (02-03-A-05), Life Phenomena and Function Research Group Program-2000 from the Ministry of Science & Technology, the Ministry of Health and Welfare (HMP 98-B-2-0007), Hallym Academy of Science, Hallym University, and the Brain Korea 21 (BK21) Program.


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

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Rac and p38 kinase mediate 5-lipoxygenase translocation and cell death'. Together they form a unique fingerprint.

Cite this