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.: Home > International Journal of Medical Sciences > 2009 > Volume 6 Number 4 > Akira Tokumura1, Laura D. Carbone2,3, Yasuko Yoshioka1, Junichi Morishige1, Masaki Kikuchi1, Arnold Postlethwaite2,3, and Mitchell A. Watsky4

Elevated Serum Levels of Arachidonoyl-lysophosphatidic Acid and Sphingosine 1-Phosphate in Systemic Sclerosis

Akira Tokumura1, Laura D. Carbone2,3, Yasuko Yoshioka1, Junichi Morishige1, Masaki Kikuchi1, Arnold Postlethwaite2,3, and Mitchell A. Watsky4
1. Department of Health Chemistry, Institute of Health Bioscience, The University of Tokushima Graduate School, 1–78-1 Shomachi, Tokushima 770–8505, Japan; 2. Veterans Affairs Medical Center, Memphis, Tennessee, USA; 3. Division of Rheumatology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA; 4. Department of Physiology, University of Tennessee Health Science Center, 894 Union Ave., Memphis, Tennessee, USA
Abstract :

Systemic sclerosis (SSc) is an often fatal disease characterized by autoimmunity and inflammation, leading to widespread vasculopathy and fibrosis. Lysophosphatidic acid (LPA), a bioactive phospholipid in serum, is generated from lysophospholipids secreted from activated platelets in part by the action of lysophospholipase D (lysoPLD). Sphingosine 1-phosphate (S1P), a member of the bioactive lysophospholipid family, is also released from activated platelets. Because activated platelets are a hallmark of SSc, we wanted to determine whether subjects with SSc have altered serum lysophospholipid levels or lysoPLD activity. Lysophospholipid levels were measured using mass spectrometric analysis. LysoPLD activity was determined by quantifying choline released from exogenous lysophosphatidylcholine
(LPC). The major results were that serum levels of arachidonoyl (20:4)-LPA and S1P were significantly higher in SSc subjects versus controls. Furthermore, serum LPA:LPC ratios of two different  polyunsaturated phospholipid molecular species, and also the ratio of all species combined, were significantly higher in SSc subjects versus controls. No significant differences were found between other lysophospholipid levels or lysoPLD activities. Elevated 20:4 LPA, S1P levels and polyunsaturated LPA:LPC ratios may be markers for and/or play a significant role in the etiology of SSc and may be future  pharmacological targets for SSc treatment.

Keywords :
scleroderma, lysophospholipids, LPA, S1P, LPC, lysophospholipase D, fibrosis

Date Deposited : 27 Jul 2011 13:22

Last Modified : 27 Jul 2011 13:22

Official URL: http://www.medsci.org/archive

Volume 6, Number 4, - 2009 , ISSN 1449-1907

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