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Int. J. Mol. Sci. 2017, 18(8), 1696;

Coral-Derived Natural Marine Compound GB9 Impairs Vascular Development in Zebrafish

Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
Department of Marine Biotechnology and Resources, National Sun Yat-sen University, Kaohsiung 80424, Taiwan
Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung 81342, Taiwan
Department of Biotechnology, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan
National Museum of Marine Biology and Aquarium, Pingtung 94450, Taiwan
Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University, Academia Sinica, Kaohsiung 80424, Taiwan
The authors contributed equally to this work.
Author to whom correspondence should be addressed.
Received: 25 May 2017 / Revised: 17 July 2017 / Accepted: 1 August 2017 / Published: 3 August 2017
(This article belongs to the Section Bioactives and Nutraceuticals)
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Blood vessels in vertebrates are established and genetically controlled in an evolutionarily-conserved manner during embryogenesis. Disruption of vascular growth by chemical compounds or environmental hormones may cause developmental defects. This study analyzed the vascular impacts of marine compound GB9 in zebrafish. GB9 was isolated from the marine soft coral Capnella imbricata and had shown anti-neuroinflammatory and anti-nociceptive activities. However, the role of GB9 on vascular development has not been reported. We first tested the survival rate of embryos under exogenous 5, 7.5, 10, and 15 μM GB9 added to the medium and determined a sub-lethal dosage of 10 μM GB9 for further assay. Using transgenic Tg(fli:eGFP) fish to examine vascular development, we found that GB9 treatment impaired intersegmental vessel (ISV) growth and caudal vein plexus (CVP) patterning at 25 hours post-fertilization (hpf) and 30 hpf. GB9 exposure caused pericardial edema and impaired circulation at 48–52 hpf, which are common secondary effects of vascular defects and suggest the effects of GB9 on vascular development. Apoptic cell death analysis showed that vascular defects were not caused by cell death, but were likely due to the inhibition of migration and/or proliferation by examining ISV cell numbers. To test the molecular mechanisms of vascular defects in GB9-treated embryos, we examined the expression of vascular markers and found the decreased expression of vascular specific markers ephrinb2, flk, mrc1, and stabilin. In addition, we examined whether GB9 treatment impairs vascular growth due to an imbalance of redox homeostasis. We found an enhanced effect of vascular defects during GB9 and H2O2 co-treatment. Moreover, exogenous N-acetyl-cysteine (NAC) treatment rescued the vascular defects in GB9 treated embryos. Our results showed that GB9 exposure causes vascular defects likely mediated by the imbalance of redox homeostasis. View Full-Text
Keywords: marine compound GB9; intersegmental vessel; vascular development; zebrafish; oxidative stress marine compound GB9; intersegmental vessel; vascular development; zebrafish; oxidative stress

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Song, Y.-C.; Wu, B.-J.; Chiu, C.-C.; Chen, C.-L.; Zhou, J.-Q.; Liang, S.-R.; Duh, C.-Y.; Sung, P.-J.; Wen, Z.-H.; Wu, C.-Y. Coral-Derived Natural Marine Compound GB9 Impairs Vascular Development in Zebrafish. Int. J. Mol. Sci. 2017, 18, 1696.

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