期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 50, 期 3, 页码 734-740出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2011.12.005
关键词
Ophiopogon japonicus polysaccharide; Myocardial ischemia; Sphingosine 1-phosphate; Sphingosine kinase; S1P receptor 1
资金
- Shanghai Municipal Education Committee [J50302, 09JW20]
- Shanghai Committee of Science and Technology, China [11ZR1434400, 09DZ2292000, 09DZ1973000]
- National Natural Science Foundation of China [81073065, 81173516]
- Doctoral Program of Higher Education [20103107120011]
Ophiopogon japonicus is a traditional Chinese medicine used to treat cardiovascular disease. Recent studies have confirmed the anti-ischemic properties of a water-soluble beta-D-fructan (MDG-1) from O. japonicus. The sphingosine 1-phosphate (S1P) signaling pathway is involved in its cytoprotective effects. Herein, we explore the role of the SIP signaling pathway in the anti-ischemic effect of MDG-1 and assess one possible mechanism by which it induces SIP release and sphingosine 1-phosphate receptor 1 (S1P(1)) expression in human microvascular endothelial cells (HMEC-1) and cardiomyocytes. Our evidence demonstrates that MDG-1 promotes sphingosine kinase (SPHK) activity in HMEC-1 cells. An analytical method for measuring the mass of S1P using ESI/MS/MS was developed and we found that MDG-1 increases intracellular S1P levels. Meanwhile, MDG-1 is protective during hypoxia and ischemia through mechanisms that require S1P(1) receptor activation, which was confirmed both in oxygen glucose deprivation (OGD) and coronary artery ligation models by using transfection of cloned human S1P(1) receptor and RNA interference. These data indicate that the increase of intracellular S1P generation, particularly by activation of the SPHK enzyme, coupled with the autocrine and paracrine stimulation of cell surface S1P receptors, is a potential mechanism in the anti-ischemic and cell protective effect of MDG-1. (C) 2011 Elsevier B.V. All rights reserved.
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