J. Lipid Res.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Originally published In Press as doi:10.1194/jlr.M600280-JLR200 on August 9, 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
M600280-JLR200v1
47/11/2462    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Butovich, I. A.
Right arrow Articles by Bachmann, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Butovich, I. A.
Right arrow Articles by Bachmann, C.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Journal of Lipid Research, Vol. 47, 2462-2474, November 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Dihydroxydocosahexaenoic acids of the neuroprotectin D family: synthesis, structure, and inhibition of human 5-lipoxygenase

Igor A. Butovich1,*, Svetlana M. Lukyanova* and Carl Bachmann{dagger}

* Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057
{dagger} Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390-9057

Published, JLR Papers in Press, August 9, 2006.

1 To whom correspondence should be addressed. e-mail: igor.butovich{at}utsouthwestern.edu

During aerobic oxidation of docosahexaenoic acid (DHA), soybean lipoxygenase (sLOX) has been shown to form 7,17(S)-dihydro(pero)xydocosahexaenoic acid [7,17(S)-diH(P)DHA] along with its previously described positional isomer, 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid. 7,17(S)-diH(P)DHA was also obtained via sLOX-catalyzed oxidation of either 17(S)-hydroperoxydocosahexaenoic acid [17(S)-HPDHA] or 17(S)-hydroxydocosahexaenoic acid [17(S)-HDHA]. The structures of the products were elucidated by normal-phase, reverse-phase, and chiral-phase HPLC analyses and by ultraviolet, NMR, and tandem mass spectroscopy and GC-MS. 7,17(S)-diH(P)DHA was shown to have 4Z,8E,10Z,13Z,15E,19Z geometry of the double bonds. In addition, a compound apparently identical to the sLOX-derived 7,17(S)-diH(P)DHA was produced by another enzyme, potato tuber LOX, in the reactions of oxygenation of either 17(S)-HPDHA or 17(S)-HDHA. All of the dihydroxydocosahexaenoic acids (diHDHAs) formed by either of the enzymes were clearly produced through double lipoxygenation of the corresponding substrate. 7,17(S)-diHDHA inhibited human recombinant 5-lipoxygenase in the reaction of arachidonic acid (AA) oxidation. In standard conditions with 100 µM AA as substrate, the IC50 value for 7,17(S)-diHDHA was found to be 7 µM, whereas IC50 for 10,17(S)-DiHDHA was 15 µM. Similar inhibition by the diHDHAs was observed with sLOX, a quintessential 15LOX, although the strongest inhibition was produced by 10,17(S)-diHDHA (IC50 = 4 µM). Inhibition of sLOX by 7,17(S)-diHDHA was slightly less potent, with an IC50 value of 9 µM. These findings suggest that 7,17(S)-diHDHA along with its 10,17(S) counterpart might have anti-inflammatory and anticancer activities, which could be exerted, at least in part, through direct inhibition of 5LOX and 15LOX.

Supplementary key words 10,17-dihydroxydocosahexaenoic acid • 7,17-dihydroxydocosahexaenoic acid • docosahexaenoic acid • double lipoxygenation • neuroprotectins D1 and D5 • protectins D1 and D5

Abbreviations: AA, arachidonic acid; BSTFA, bis(trimethylsilyl)trifluoroacetamide; DHA, docosahexaenoic acid; diHDA, dihydroxydocosanoic acid; diHDHA, dihydroxydocosahexaenoic acid; hr5LOX, human recombinant 5-lipoxygenase; NP, normal-phase; PD1, protectin D1; ptLOX, potato tuber lipoxygenase; RP, reverse-phase; RT, retention time; sLOX, soybean lipoxygenase; 10,17(S)-diH(P)DHA, 10,17(S)-dihydro(pero)xydocosahexa-4Z,7Z,11E,13Z,15E,19Z-enoic acid; 7,17(S)-diH(P)DHA, 7,17(S)-dihydro(pero)xydocosahexaenoic acid; 17(S)-H(P)DHA, 17(S)-hydro(pero)xydocosahexa-4Z,7Z,11Z,13Z,15E,19Z-enoic acid; 5(S)-HPETE, 5(S)-hydroperoxyeicosatetraenoic acid; 13(S)-HPODE, 13(S)-hydroperoxyoctadecadi-9Z,11E-enoic acid; UV, ultraviolet


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Lipid Res.Home page
I. A. Butovich and S. M. Lukyanova
Inhibition of lipoxygenases and cyclooxygenases by linoleyl hydroxamic acid: comparative in vitro studies
J. Lipid Res., June 1, 2008; 49(6): 1284 - 1294.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Journal of Biological Chemistry 
 Molecular and Cellular Proteomics   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.