HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 7, 4222-4230, February 17, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/7/4222    most recent M509769200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Sun, M. Articles by Hazen, S. L. Search for Related Content PubMed PubMed Citation Articles by Sun, M. Articles by Hazen, S. L. Social Bookmarking                      What's this?

Light-induced Oxidation of Photoreceptor Outer Segment Phospholipids Generates Ligands for CD36-mediated Phagocytosis by Retinal Pigment Epithelium

A POTENTIAL MECHANISM FOR MODULATING OUTER SEGMENT PHAGOCYTOSIS UNDER OXIDANT STRESS CONDITIONS^*

Mingjiang Sun, Silvia C. Finnemann^¶1, Maria Febbraio, Lian Shan, Suresh P. Annangudi, Eugene A. Podrez, George Hoppe^||, Ruth Darrow^**, Daniel T. Organisciak^**, Robert G. Salomon, Roy L. Silverstein, and Stanley L. Hazen²

From the Department of Chemistry, Case Western Reserve University, Cleveland, Cleveland, Ohio 44106, the Departments of Cell Biology and Cardiovascular Medicine and the Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, Cleveland, Ohio 44195, the ^¶Dyson Vision Research Institute, Department of Ophthalmology, Department of Cell and Developmental Biology, and Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York 10021, the ^||Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, and the ^**Department of Biochemistry and Molecular Biology, Wright State University School of Medicine, Dayton, Ohio 45401-0927

Clearance by the retinal pigment epithelium (RPE) of shed photoreceptor outer segments (OSs), a tissue with one of the highest turnover rates in the body, is critical to the maintenance and normal function of the retina. We hypothesized that there is a potential role for photo-oxidation in OS uptake by RPE via scavenger receptor-mediated recognition of structurally defined lipid peroxidation products. We now demonstrate that specific structurally defined oxidized species derived from arachidonyl, linoleoyl, and docosahexanoyl phosphatidylcholine may serve as endogenous ligands on OSs for uptake by RPE via the scavenger receptor CD36. Mass spectrometry studies of retinal lipids recovered from dark-adapted rats following physiological light exposure demonstrate in vivo formation of specific oxidized phosphatidylcholine molecular species possessing a CD36 recognition motif, an oxidatively truncated sn-2 acyl group with a terminal -hydroxy(or oxo)-,-unsaturated carbonyl. Cellular studies using RPE isolated from wild-type versus CD36 null mice suggest that CD36 plays a role in engulfment, but not initial binding, of OSs via these oxidized phospholipids. Parallel increases in OS protein-bound nitrotyrosine, a post-translational modification by nitric oxide (NO)-derived oxidants, were also observed, suggesting a possible role for light-induced generation of NO-derived oxidants in the initiation of OS lipid peroxidation. Collectively, these studies suggest that intense light exposure promotes "oxidative tagging" of photoreceptor outer segments with structurally defined choline glycerophospholipids that may serve as a physiological signal for CD36-mediated phagocytosis under oxidant stress conditions.

Received for publication, September 6, 2005 , and in revised form, December 13, 2005.

^* This work was supported in part by National Institutes of Health Grants P01 HL076491, P01 HL77107, HL70621, HL61878, EY10967, HL46403, EY13295, and EY01959 and by the Cleveland Clinic Foundation General Clinical Research Center (Grant M01 RR018390). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ The Research To Prevent Blindness William & Mary Greve Scholar and the recipient of an Irma T. Hirschl Career Scientist Award.

² To whom correspondence should be addressed: Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic Foundation, 9500 Euclid Ave., NE-10, Cleveland, OH 44195. Tel.: 216-445-9763; Fax: 216-636-0392; E-mail: hazens{at}ccf.org.

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

This article has been cited by other articles:

				R. L. Silverstein and M. Febbraio CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and Behavior Sci. Signal., May 26, 2009; 2(72): re3 - re3. [Abstract] [Full Text] [PDF]

				S. L. Hazen Oxidized Phospholipids as Endogenous Pattern Recognition Ligands in Innate Immunity J. Biol. Chem., June 6, 2008; 283(23): 15527 - 15531. [Full Text] [PDF]

				X. Chen, W. Zhang, J. Laird, S. L. Hazen, and R. G. Salomon Polyunsaturated phospholipids promote the oxidation and fragmentation of {gamma}-hydroxyalkenals: formation and reactions of oxidatively truncated ether phospholipids J. Lipid Res., April 1, 2008; 49(4): 832 - 846. [Abstract] [Full Text] [PDF]

				N. S. Kar, M. Z. Ashraf, M. Valiyaveettil, and E. A. Podrez Mapping and Characterization of the Binding Site for Specific Oxidized Phospholipids and Oxidized Low Density Lipoprotein of Scavenger Receptor CD36 J. Biol. Chem., March 28, 2008; 283(13): 8765 - 8771. [Abstract] [Full Text] [PDF]

				M. E. Greenberg, X.-M. Li, B. G. Gugiu, X. Gu, J. Qin, R. G. Salomon, and S. L. Hazen The Lipid Whisker Model of the Structure of Oxidized Cell Membranes J. Biol. Chem., January 25, 2008; 283(4): 2385 - 2396. [Abstract] [Full Text] [PDF]

				N. G. Bazan Homeostatic Regulation of Photoreceptor Cell Integrity: Significance of the Potent Mediator Neuroprotectin D1 Biosynthesized from Docosahexaenoic Acid The Proctor Lecture Invest. Ophthalmol. Vis. Sci., November 1, 2007; 48(11): 4866 - 4881. [Full Text] [PDF]

				P. K. Mukherjee, V. L. Marcheselli, J. C. de Rivero Vaccari, W. C. Gordon, F. E. Jackson, and N. G. Bazan Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis PNAS, August 7, 2007; 104(32): 13158 - 13163. [Abstract] [Full Text] [PDF]

				E. Kaemmerer, F. Schutt, T. U. Krohne, F. G. Holz, and J. Kopitz Effects of Lipid Peroxidation-Related Protein Modifications on RPE Lysosomal Functions and POS Phagocytosis Invest. Ophthalmol. Vis. Sci., March 1, 2007; 48(3): 1342 - 1347. [Abstract] [Full Text] [PDF]

				S. Gao, R. Zhang, M. E. Greenberg, M. Sun, X. Chen, B. S. Levison, R. G. Salomon, and S. L. Hazen Phospholipid Hydroxyalkenals, a Subset of Recently Discovered Endogenous CD36 Ligands, Spontaneously Generate Novel Furan-containing Phospholipids Lacking CD36 Binding Activity in Vivo J. Biol. Chem., October 20, 2006; 281(42): 31298 - 31308. [Abstract] [Full Text] [PDF]