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

J. Biol. Chem., Vol. 279, Issue 51, 53395-53406, December 17, 2004

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 279/51/53395    most recent M403416200v1 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 Srivastava, S. Articles by Bhatnagar, A. Search for Related Content PubMed PubMed Citation Articles by Srivastava, S. Articles by Bhatnagar, A. Social Bookmarking                      What's this?

Aldose Reductase-catalyzed Reduction of Aldehyde Phospholipids^*

Sanjay Srivastava, Matthew Spite, John O. Trent, Matthew B. West, Yonis Ahmed, and Aruni Bhatnagar¶

From the Institute of Molecular Cardiology and the James Brown Cancer Center, Department of Medicine, University of Louisville, Louisville, Kentucky 40202

Oxidation of unsaturated phospholipids results in the generation of aldehyde side chains that remain esterified to the phospholipid backbone. Such "core" aldehydes elicit immune responses and promote inflammation. However, the biochemical mechanisms by which phospholipid aldehydes are metabolized or detoxified are not well understood. In the studies reported here, we examined whether aldose reductase (AR), which reduces hydrophobic aldehydes, metabolizes phospholipid aldehydes. Incubation with AR led to the reduction of 5-oxovaleroyl, 7-oxo-5-heptenoyl, 5-hydroxy-6-oxo-caproyl, and 5-hydroxy-8-oxo-6-octenoyl phospholipids generated upon oxidation of 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (PAPC). The enzyme also catalyzed the reduction of phospholipid aldehydes generated from the oxidation of 1-alkyl, and 1-alkenyl analogs of PAPC, and 1-palmitoyl-2-arachidonoyl phosphatidic acid or phosphoglycerol. Aldose reductase catalyzed the reduction of chemically synthesized 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphatidylcholine (POVPC) with a K_m of 10 µM. Addition of POVPC to the culture medium led to incorporation and reduction of the aldehyde in COS-7 and THP-1 cells. Reduction of POVPC in these cells was prevented by the AR inhibitors sorbinil and tolrestat and was increased in COS-7 cells overexpressing AR. Together, these observations suggest that AR may be a significant participant in the metabolism of several structurally diverse phospholipid aldehydes. This metabolism may be a critical regulator of the pro-inflammatory and immunogenic effects of oxidized phospholipids.

Received for publication, March 29, 2004 , and in revised form, September 28, 2004.

^* This work was supported in part by National Institutes of Health Grants HL55477, HL59378, ES11860 (to A. B.) and HL65618 (to S. S.). 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.

The on-line version of this article (available at http://www.jbc.org) contains Supplemental Materials.

^¶ To whom correspondence should be addressed: Division of Cardiology, Dept. of Medicine, Delia Baxter Bldg., 580 S. Preston St., Room 421F, University of Louisville, Louisville, KY 40202. Tel.: 502-852-5966; Fax: 502-852-3663; E-mail: aruni{at}louisville.edu.

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

This article has been cited by other articles:

				J. C. States, S. Srivastava, Y. Chen, and A. Barchowsky Arsenic and Cardiovascular Disease Toxicol. Sci., February 1, 2009; 107(2): 312 - 323. [Abstract] [Full Text] [PDF]

				K. Kaiserova, X.-L. Tang, S. Srivastava, and A. Bhatnagar Role of Nitric Oxide in Regulating Aldose Reductase Activation in the Ischemic Heart J. Biol. Chem., April 4, 2008; 283(14): 9101 - 9112. [Abstract] [Full Text] [PDF]

				A.-L. Levonen, M. Inkala, T. Heikura, S. Jauhiainen, H.-K. Jyrkkanen, E. Kansanen, K. Maatta, E. Romppanen, P. Turunen, J. Rutanen, et al. Nrf2 Gene Transfer Induces Antioxidant Enzymes and Suppresses Smooth Muscle Cell Growth In Vitro and Reduces Oxidative Stress in Rabbit Aorta In Vivo Arterioscler. Thromb. Vasc. Biol., April 1, 2007; 27(4): 741 - 747. [Abstract] [Full Text] [PDF]

				A. Pladzyk, A. B. M. Reddy, U. C. S. Yadav, R. Tammali, K. V. Ramana, and S. K. Srivastava Inhibition of Aldose Reductase Prevents Lipopolysaccharide-Induced Inflammatory Response in Human Lens Epithelial Cells Invest. Ophthalmol. Vis. Sci., December 1, 2006; 47(12): 5395 - 5403. [Abstract] [Full Text] [PDF]

				K. V. Ramana, M. S. Willis, M. D. White, J. W. Horton, J. M. DiMaio, D. Srivastava, A. Bhatnagar, and S. K. Srivastava Endotoxin-Induced Cardiomyopathy and Systemic Inflammation in Mice Is Prevented by Aldose Reductase Inhibition Circulation, October 24, 2006; 114(17): 1838 - 1846. [Abstract] [Full Text] [PDF]

				K. Kaiserova, S. Srivastava, J. D. Hoetker, S. O. Awe, X.-L. Tang, J. Cai, and A. Bhatnagar Redox Activation of Aldose Reductase in the Ischemic Heart J. Biol. Chem., June 2, 2006; 281(22): 15110 - 15120. [Abstract] [Full Text] [PDF]

				S. K. Srivastava, K. V. Ramana, and A. Bhatnagar Role of Aldose Reductase and Oxidative Damage in Diabetes and the Consequent Potential for Therapeutic Options Endocr. Rev., May 1, 2005; 26(3): 380 - 392. [Abstract] [Full Text] [PDF]