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


     

This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
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 Shen, J.
Right arrow Articles by Chan, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, J.
Right arrow Articles by Chan, L.

The FASEB Journal, Vol 9, 1623-1631, Copyright © 1995 by The Federation of American Societies for Experimental Biology

RESEARCH COMMUNICATIONS

Transgenic rabbits with the integrated human 15-lipoxygenase gene driven by a lysozyme promoter: macrophage-specific expression and variable positional specificity of the transgenic enzyme

J Shen, H Kuhn, A Petho-Schramm and L Chan
Department of Cell Biology, Baylor College of Medicine, Houston, Texas 77030, USA.

15-Lipoxygenase is expressed in foamy macrophages of atherosclerotic lesions and has been implicated in the oxidative modification of low density lipoprotein during early stages of atherogenesis. To establish an animal model of 15-lipoxygenase overexpression, we created transgenic rabbits that express at high level the human 15-lipoxygenase in monocyte-derived macrophages but not in liver, heart, kidney, lung, or other tissues. The expression level of the enzyme in monocyte- derived macrophages is comparable to that of interleukin 4 (IL4)- treated human monocytes, but more than 20-fold higher than in macrophages of normal rabbits. The transgenic enzyme oxygenates linoleic acid to 13S-hydroperoxy-9, 11 (Z,E)-octadecadienoic acid (13- HODE), and arachidonic acid to a mixture of 12S-hydroperoxy-5, 8, 10, 14 (Z,Z,E,Z)-eicosatetraenoic acid (12S-HETE), and 15S-hydroperoxy-5, 8, 11, 14 (Z,Z,Z,E)-eicosatetraenoic acid (15S-HETE). The 12-HETE/15- HETE ratio varied between 0.3 and 5.4, indicating a remarkable variability in the positional specificity of the transgenic enzyme. Macrophages from normal rabbits consistently produced 12S-HETE as the major oxygenation product. 15-Lipoxygenase-overexpressing rabbits may be used for further mechanistic studies on the implication of lipoxygenase in atherogenesis; they are also an ideal model for testing the in vivo action of 15-lipoxygenase inhibitors.


This article has been cited by other articles:


Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
D. Teupser, D. Kretzschmar, C. Tennert, R. Burkhardt, W. Wilfert, D. Fengler, R. Naumann, A. E. Sippel, and J. Thiery
Effect of Macrophage Overexpression of Murine Liver X Receptor-{alpha} (LXR-{alpha}) on Atherosclerosis in LDL-Receptor Deficient Mice
Arterioscler. Thromb. Vasc. Biol., November 1, 2008; 28(11): 2009 - 2015.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
Y. Huo, L. Zhao, M. C. Hyman, P. Shashkin, B. L. Harry, T. Burcin, S. B. Forlow, M. A. Stark, D. F. Smith, S. Clarke, et al.
Critical Role of Macrophage 12/15-Lipoxygenase for Atherosclerosis in Apolipoprotein E-Deficient Mice
Circulation, October 5, 2004; 110(14): 2024 - 2031.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Zhu, Y. Takahashi, W. Xu, H. Kawajiri, T. Murakami, M. Yamamoto, S. Iseki, T. Iwasaki, H. Hattori, and T. Yoshimoto
Low Density Lipoprotein Receptor-related Protein-mediated Membrane Translocation of 12/15-Lipoxygenase Is Required for Oxidation of Low Density Lipoprotein by Macrophages
J. Biol. Chem., April 4, 2003; 278(15): 13350 - 13355.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
S. C. Whitman, D. L. Rateri, S. J. Szilvassy, J. A. Cornicelli, and A. Daugherty
Macrophage-specific expression of class A scavenger receptors in LDL receptor-/- mice decreases atherosclerosis and changes spleen morphology
J. Lipid Res., August 1, 2002; 43(8): 1201 - 1208.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
A. Daugherty, N. Kosswig, J. A. Cornicelli, S. C. Whitman, S. Wolle, and D. L. Rateri
Macrophage-specific expression of class A scavenger receptors enhances granuloma formation in the absence of increased lipid deposition
J. Lipid Res., July 1, 2001; 42(7): 1049 - 1055.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
D. Harats, A. Shaish, J. George, M. Mulkins, H. Kurihara, H. Levkovitz, and E. Sigal
Overexpression of 15-Lipoxygenase in Vascular Endothelium Accelerates Early Atherosclerosis in LDL Receptor-Deficient Mice
Arterioscler. Thromb. Vasc. Biol., September 1, 2000; 20(9): 2100 - 2105.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Reynaud, M. Ali, P. Demin, and C. R. Pace-Asciak
Formation of 14,15-Hepoxilins of the A3 and B3 Series through a 15-Lipoxygenase and Hydroperoxide Isomerase Present in Garlic Roots
J. Biol. Chem., October 1, 1999; 274(40): 28213 - 28218.
[Abstract] [Full Text] [PDF]

Home page
 J. Lipid Res.Home page
X. Fang, T. L. Kaduce, and A. A. Spector
13-(S)-Hydroxyoctadecadienoic acid (13-HODE) incorporation and conversion to novel products by endothelial cells
J. Lipid Res., April 1, 1999; 40(4): 699 - 707.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
J. Belkner, H. Stender, and H. Kuhn
The Rabbit 15-Lipoxygenase Preferentially Oxygenates LDL Cholesterol Esters, and This Reaction Does Not Require Vitamin E
J. Biol. Chem., September 4, 1998; 273(36): 23225 - 23232.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 1995 by The Federation of American Societies for Experimental Biology.