Antioxidants inhibit the ability of lysophosphatidylcholine to regulate proteoglycan synthesis.
OBJECTIVE
We previously have shown that lysophosphatidylcholine (lysoPC) regulates proteoglycan synthesis by vascular smooth muscle cells (SMCs). Given the accumulating evidence for reactive oxygen species (ROS) as mediators of a variety of effects of lysoPC, the present study evaluates the potential role of ROS as intermediate molecules in the regulation of proteoglycan synthesis by lysoPC.


RESULTS
LysoPC (10 micromol/L) was found to stimulate rapid and sustained generation of ROS by SMC, as indicated using a fluorescent probe for measuring intracellular oxidants and fluorescence-activated cell sorting. This was not associated with cytotoxicity, as evaluated by fluorescence microscopy using MitoTracker Red or propidium iodide, cell number, cell protein, or lactate dehydrogenase release. Pretreatment with catalase or superoxide dismutase, specific scavengers of hydrogen peroxide and superoxide, respectively, blocked the ability of lysoPC to stimulate both accumulation of ROS and proteoglycan synthesis. Most importantly, these enzymatic antioxidants prevented lysoPC from stimulating the synthesis of proteoglycans with enhanced lipoprotein-binding properties, as quantified by a gel shift binding assay.


CONCLUSIONS
These findings strongly suggest that ROS are key mediators in the ability of lysoPC to regulate proteoglycan synthesis and that these effects can be inhibited by antioxidants.
Chang
Mary Y
MY
Department of Medicine, University of Washington, Seattle, WA 98195-6426, USA. mychang@u.washington.edu
Han
Chang-Yeop
CY
Wight
Thomas N
TN
Chait
Alan
A
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002374:Catalase / Q000494:pharmacology; D002478:Cells, Cultured; D004347:Drug Interactions; D016166:Free Radical Scavengers / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008254:Macaca nemestrina; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011509:Proteoglycans / Q000096:biosynthesis* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology
D000975:Antioxidants; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D011509:Proteoglycans; D017382:Reactive Oxygen Species; D002374:Catalase; D013482:Superoxide Dismutase