Colominic acid inhibits the proliferation of cultured bovine aortic endothelial cells and injures their monolayers: cell density-dependent effects prevented by sulfation |
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Authors: | Yamamoto Chika Morita Yuki Yamaguchi Shinya Hayashi Toshimitsu Kaji Toshiyuki |
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Affiliation: | Department of Environmental Health, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-1181, Japan. |
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Abstract: | Colominic acid (CA), produced by Escherichia coli K1, is a polymer of sialic acid linked through alpha (2-->8) glycosidic linkages. Although there are several studies on the biological activities of chemically sulfated CA, the activity of CA has been incompletely understood. In the present study, we investigated the effects of CA, prepared as an alpha2,8-linked homopolymer of N-acetylneuraminic acid, on the proliferation and monolayer maintenance of bovine aortic endothelial cells in culture. The results indicate that CA potently inhibits the proliferation of sparse endothelial cells without nonspecific cell damage. The inhibitory effect of CA was markedly stronger than those of sodium spirulan and calcium spirulan, known polysaccharides that inhibit endothelial cell proliferation. On the other hand, in dense endothelial cells, CA induced nonspecific cell damage and markedly injured the monolayer. These results indicate that CA has two distinct effects on vascular endothelial cells: one is the inhibition of proliferation when the cell density is low, and the other is the nonspecific cytotoxicity when the cell density is high. Interestingly, these cell density-dependent effects of CA could be prevented by sulfation of the CA chains. Therefore, it is concluded that CA not only inhibits the proliferation of sparse endothelial cells without nonspecific cell damage but also injures dense cells in a monolayer by nonspecific cytotoxicity, which can be prevented by sulfation of the polysaccharide. |
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Keywords: | CA, colominic acid Ca-SP, calcium spirulan CMF-PBS, Ca2+- and Mg2+-free phosphate-buffered saline DMEM, Dulbecco's modified Eagle's medium EDTA, ethylenediaminetetraacetic acid FGF-2, fibroblast growth factor-2 Na-SP, sodium spirulan PAI-1, plasminogen activator inhibitor type 1 SCA, O-sulfated colominic acid SCA2.4, O-sulfated colominic acid with a sulfur content of 2.4% SCA7.5, O-sulfated colominic acid with a sulfur content of 7.5% SCA13.4, O-sulfated colominic acid with a sulfur content of 13.4% |
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