Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways

Xi-Lin Lu; Zhong-Liang Xu; Xiao-Li Yao; Feng-Juan Su; Cheng-Hui Ye; Jing Li; Yong-Cheng Lin; Guang-Lei Wang; Jin-Sheng Zeng; Ru-Xun Huang; Jing-Song Ou; Hong-Shuo Sun; Li-Ping Wang; Ji-Yan Pang; Zhong Pei

doi:10.3390/md10061307

Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways

Mar Drugs. 2012 Jun;10(6):1307-1320. doi: 10.3390/md10061307. Epub 2012 Jun 7.

Authors

Xi-Lin Lu¹, Zhong-Liang Xu², Xiao-Li Yao¹, Feng-Juan Su¹, Cheng-Hui Ye¹, Jing Li², Yong-Cheng Lin², Guang-Lei Wang^{3

4}, Jin-Sheng Zeng¹, Ru-Xun Huang¹, Jing-Song Ou^{5

6}, Hong-Shuo Sun⁷, Li-Ping Wang⁸, Ji-Yan Pang², Zhong Pei¹

Affiliations

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.

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; endothelial nitric oxide synthase; marine cyclotripeptide; xyloallenoide A; zebrafish.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Angiogenesis Inducing Agents / chemical synthesis
Angiogenesis Inducing Agents / chemistry
Angiogenesis Inducing Agents / isolation & purification
Angiogenesis Inducing Agents / pharmacology*
Animals
Aquatic Organisms / chemistry*
Biological Products / chemical synthesis
Biological Products / chemistry
Biological Products / isolation & purification
Biological Products / pharmacology
Cell Line
Chromones / pharmacology
Endothelial Cells / drug effects
Endothelial Cells / metabolism
Fungi / chemistry
Human Umbilical Vein Endothelial Cells
Humans
Morpholines / pharmacology
NG-Nitroarginine Methyl Ester / pharmacology
Neovascularization, Physiologic / drug effects*
Nitric Oxide / metabolism
Nitric Oxide Synthase Type III / antagonists & inhibitors
Nitric Oxide Synthase Type III / metabolism*
Phosphatidylinositol 3-Kinases / metabolism*
Phosphoinositide-3 Kinase Inhibitors
Phosphorylation / drug effects
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / metabolism*
Signal Transduction / drug effects*
Zebrafish / metabolism

Substances

Angiogenesis Inducing Agents
Biological Products
Chromones
Morpholines
Phosphoinositide-3 Kinase Inhibitors
Nitric Oxide
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Nitric Oxide Synthase Type III
Proto-Oncogene Proteins c-akt
NG-Nitroarginine Methyl Ester