期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 488, 期 1-3, 页码 11-18出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2004.01.033
关键词
neuronal PC12D cells; nerve growth factor; survival supportiiig activity; neurite regeneration; phosphatidylinositol-3 kinase; sargaquinoic acid
Sargaquinoic acid (designated previously as MC14) was isolated from a marine brown alga Sargassum macrocarpum, and has been found to possess a novel nerve growth factor (NGF)-dependent neurite outgrowth promoting activity in PC I 2D cells. In this study, we explored the neuroprotective effects of MC14 in terms of its survival supporting, antioxidant and neurite-regenerating activities under NGF deficient or deprived conditions. Intriguingly, MC14 did not only promote the NGF-induced survival support on neuronal PC12D cells, but also significantly abated neuronal PC I 2D cell death even in the absence of NGF. The pharmacological inhibition of phosphatidylinositol-3 kinase (PI3K) by wortmannin significantly suppressed the survival supporting activity of MC14, whereas the NGF receptor (tyrosine kinase A or TrkA) inhibitor K252a showed no detectable effect on MC14 activity. These results demonstrate that MC14 supports survival of neuronal PC12D cells in an NGF-independent manner, and that PI3K may be required for the neuroprotective activity of MC14. In addition, we have shown that MC14 markedly enhanced neurite-regeneration and protected PC12D cells from hydrogen peroxide (H2O2)-induced oxidative stress. These pharmacological features suggest that MC14 may be a potentially important neuroprotective agent. (C) 2004 Elsevier B.V. All rights reserved.
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