Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6)

Bindi Dangi, Marcus Obeng, Julie M Nauroth, Mah Teymourlouei, Micah Needham, Krishna Raman, Linda M. Arterburn

Research output: Contribution to journalArticle

Abstract

Enzymatically oxygenated derivatives of the ω-3 fatty acids cis-4,7,10,13,16,19-docosahexaenoic acid (DHA) and cis-5,8,11,14,17 -eicosapentaenoic acid, known as resolvins, have potent inflammation resolution activity (Serhan, C. N., Clish, C. B., Brannon, J., Colgan, S. P., Chiang, N., and Gronert, K. (2000) J. Exp. Med. 192, 1197-1204; Hong, S., Gronert, K., Devchand, P. R., Moussignac, R., and Serhan, C. N. (2003) J. Biol. Chem. 278, 14677-14687). Our objective was to determine whether similar derivatives are enzymatically synthesized from other C-22 fatty acids and whether these molecules possess inflammation resolution properties. The reaction of DHA, DPAn-3, and DPAn-6 with 5-, 12-, and 15-lipoxygenases produced oxylipins, which were identified and characterized by liquid chromatography coupled with tandem mass-spectrometry. DPAn-6 and DPAn-3 proved to be good substrates for 15-lipoxygenase. 15-Lipoxygenase proved to be the most efficient enzyme of the three tested for conversion of long chain poly-unsaturated fatty acids to corresponding oxylipins. Since DPAn-6 is a major component of Martek DHA-S™ oil, we focused our attention on reaction products obtained from the DPAn-6 and 15-lipoxygenase reaction. (17S)-hydroxy-DPAn-6 and (10,17S)- dihydroxy-DPAn-6 were the main products of this reaction. These compounds were purified by preparatory high performance liquid chromatography techniques and further characterized by NMR, UV spectrophotometry, and tandem mass spectrometry. We tested both compounds in two animal models of acute inflammation and demonstrated that both compounds are potent anti-inflammatory agents that are active on local intravenous as well as oral administration. These oxygenated DPAn-6 compounds can thus be categorized as a new class of DPAn-6-derived resolvins.

Original languageEnglish (US)
Pages (from-to)14744-14759
Number of pages16
JournalJournal of Biological Chemistry
Volume284
Issue number22
DOIs
StatePublished - May 29 2009
Externally publishedYes

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Arachidonate 15-Lipoxygenase
Docosahexaenoic Acids
Oxylipins
Purification
Anti-Inflammatory Agents
Tandem Mass Spectrometry
Inflammation
Mass spectrometry
Fatty Acids
Polyunsaturated fatty acids
Derivatives
Eicosapentaenoic Acid
Spectrophotometry
Liquid chromatography
High performance liquid chromatography
Unsaturated Fatty Acids
Reaction products
Liquid Chromatography
Intravenous Administration
Oral Administration

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6). / Dangi, Bindi; Obeng, Marcus; Nauroth, Julie M; Teymourlouei, Mah; Needham, Micah; Raman, Krishna; Arterburn, Linda M.

In: Journal of Biological Chemistry, Vol. 284, No. 22, 29.05.2009, p. 14744-14759.

Research output: Contribution to journalArticle

Dangi, Bindi ; Obeng, Marcus ; Nauroth, Julie M ; Teymourlouei, Mah ; Needham, Micah ; Raman, Krishna ; Arterburn, Linda M. / Biogenic synthesis, purification, and chemical characterization of anti-inflammatory resolvins derived from docosapentaenoic acid (DPAn-6). In: Journal of Biological Chemistry. 2009 ; Vol. 284, No. 22. pp. 14744-14759.
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AU - Needham, Micah

AU - Raman, Krishna

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