Convergence of the 5-LOX and COX-2 pathways: Heme-catalyzed cleavage of the 5S-HETE-derived di-endoperoxide into aldehyde fragments

Markus Griesser, William E. Boeglin, Takashi Suzuki, Claus Schneider

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

Oxygenation of the 5-lipoxygenase product 5 S-hydroxyeicosatetraenoic acid by cyclooxygenase-2 yields a bicyclic di-endoperoxide. The di-endoperoxide contains two peroxides spanning from carbons 9 to 11 and 8 to 12, and two hydroxyls at carbons 5 and 15 of arachidonic acid (Schneider C., et al. 2006. Convergent oxygenation of arachidonic acid by 5-lipoxygenase and cyclooxygenase-2. J. Am. Chem. Soc. 128: 720). Here, we report that treatment of the di-endoperoxide with hematin or ferrous chloride results in cleavage of both peroxide O-O bonds and of the bonds between the carbons that carry the peroxide groups, producing the aldehydes 4-hydroxy-2 E -nonenal (4-HNE), 8-oxo-5 S -hydroxy-6 E -octenoic acid, and malondialdehyde (MDA). The hematin- and ferrous iron-catalyzed transformation of the di-endoperoxide proceeded with a similar yield of products as the cleavage of the prostaglandin endoperoxide PGH2 to 12S-hydroxy-5Z,8E,10E-heptadecatrienoic acid and MDA. Chiral phase HPLC analysis of the 4-HNE cleavage product showed greater than 98% 4S and thus established the S confi guration of the 15-carbon of the di-endoperoxide that had not previously been assigned. This transformation of the 5-lipoxygenase/cyclooxygenase-2 derived di-endoperoxide invokes the possibility of a novel pathway to formation of the classic lipid peroxidation products 4-HNE and MDA.

Original languageEnglish (US)
Pages (from-to)2455-2462
Number of pages8
JournalJournal of lipid research
Volume50
Issue number12
DOIs
StatePublished - Dec 1 2009
Externally publishedYes

Keywords

  • 4-hydroxy-nonenal
  • Aldehyde
  • Lipid peroxide
  • Malondialdehyde
  • Prostaglandin

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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