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

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.

journal_name

Int J Mol Sci

journal_title

International journal of molecular sciences

authors

Song YC,Wu BJ,Chiu CC,Chen CL,Zhou JQ,Liang SR,Duh CY,Sung PJ,Wen ZH,Wu CY

doi

10.3390/ijms18081696

subject

Has Abstract

pub_date

2017-08-03 00:00:00

issue

issn

1422-0067

pii

ijms18081696

journal_volume

pub_type

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