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Mar. Drugs 2012, 10(6), 1307-1320; doi:10.3390/md10061307
Article

Marine Cyclotripeptide X-13 Promotes Angiogenesis in Zebrafish and Human Endothelial Cells via PI3K/Akt/eNOS Signaling Pathways

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1 Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China 2 School of Chemistry & Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China 3 Department of Pharmacology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China 4 Key Laboratory of Functional Molecules from Oceanic Microorganisms, Department of Education of Guangdong Province, Guangzhou 510080, China 5 Division of Cardiac Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China 6 The Key Laboratory of Assisted Circulation, Ministry of Health, Guangzhou 510182, China 7 Division of Anatomy, Department of Surgery, Institute of Medical Science, Faculty of Medicine, University of Toronto, Toronto, ON M5G 1G6, Canada 8 Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 4 March 2012 / Revised: 8 May 2012 / Accepted: 29 May 2012 / Published: 7 June 2012
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Abstract

Cyclotripeptide X-13 is a core of novel marine compound xyloallenoide A isolated from mangrove fungus Xylaria sp. (no. 2508). We found that X-13 dose-dependently induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/Akt/eNOS by LY294002 or l-NAME suppressed X-13-induced angiogenesis. The present work demonstrates that X-13 promotes angiogenesis via PI3K/Akt/eNOS pathways.
Keywords: angiogenesis; marine cyclotripeptide; zebrafish; endothelial nitric oxide synthase; xyloallenoide A angiogenesis; marine cyclotripeptide; zebrafish; endothelial nitric oxide synthase; xyloallenoide A
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Lu, X.-L.; Xu, Z.-L.; Yao, X.-L.; Su, F.-J.; Ye, C.-H.; Li, J.; Lin, Y.-C.; Wang, G.-L.; Zeng, J.-S.; Huang, R.-X.; Ou, J.-S.; Sun, H.-S.; Wang, L.-P.; Pang, J.-Y.; Pei, Z. Marine Cyclotripeptide X-13 Promotes Angiogenesis in Zebrafish and Human Endothelial Cells via PI3K/Akt/eNOS Signaling Pathways. Mar. Drugs 2012, 10, 1307-1320.

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