Abstract
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.
Highlights
Natural compounds discovered in marine organisms have drawn attention as potential sources of novel drugs for human diseases [1]
Treatment using chemicals or natural products can result in anti-proliferation and migration of endothelial cells or the death of cancer cells mediated by the increase of oxidative stress [30,31]
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Summary
Natural compounds discovered in marine organisms have drawn attention as potential sources of novel drugs for human diseases [1]. Many studies have indicated that marine natural products exhibit anti-inflammatory bioactivities that can be used to develop antiviral and anti-inflammatory drugs [2,3,4,5]. The zebrafish model has been successfully used to reveal molecular mechanisms of blood vessel formation, such as angioblast specification and differentiation, endothelial cell proliferation and migration, vessel formation, patterning, and morphogenesis [16,17,18,19,20,21,22,23]. Treatment using chemicals or natural products can result in anti-proliferation and migration of endothelial cells or the death of cancer cells mediated by the increase of oxidative stress [30,31]. Our results provide a useful reference for future examination of vascular growth during chemical treatment
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