Protamine may have anti-atherogenic potential by inhibiting the binding of oxidized-low density lipoprotein to LOX-1 |
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| Authors: | Yukitoshi Takemura Masaki Okamoto Makoto Hasegawa Kenichi Hatanaka |
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| Institution: | 1. Institute of Industrial Science, The University of Tokyo, Tokyo, Japan;2. Department of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan;3. Department of Pharmaceutical Sciences, Teikyo Heisei University, Tokyo, Japan |
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| Abstract: | Oxidized low-density lipoprotein (ox-LDL) leads to atherosclerosis via lectin-like oxidized lipoprotein receptor-1 (LOX-1), one of the major receptor for ox-LDL. Inhibition of the binding of ox-LDL to LOX-1 decreases the proinflammatory and atherosclerotic events. The aim of the present study was to investigate whether protamine, a polybasic nuclear protein, interferes the binding of ox-LDL to LOX-1. Using sandwich ELISA with newly generated antibody, we measured the blocking effect of protamine on the binding of ox-LDL to LOX-1. Protamine dose-dependently inhibited the binding of ox-LDL to LOX-1. DiI-labeled ox-LDL uptake assay in two types of cultured human endothelial cells was performed with fluorescence microplate reader. Activation of extracellular-signal-regulated kinase (ERK)1/2 by ox-LDL was analyzed by immunoblotting. We found that protamine suppressed uptake of ox-LDL in endothelial cells and inhibited ERK1/2 activation by ox-LDL. These results suggest that protamine may possess anti-atherogenic potential by inhibiting ox-LDL binding to LOX-1 through electrostatic interactions. |
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| Keywords: | Protamine ox-LDL LOX-1 |
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