Title page for etd-0716117-115842


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URN etd-0716117-115842
Author Yi-Chun Song
Author's Email Address spk91326@gmail.com
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Department Biological Sciences
Year 2016
Semester 2
Degree Master
Type of Document
Language zh-TW.Big5 Chinese
Title Coral-derived natural marine compound GB9 inhibits vascular development in zebrafish
Date of Defense 2017-07-12
Page Count 66
Keyword
  • zebrafish
  • marine compound
  • angiogenesis
  • GB9
  • Abstract Vascular development is important for vertebrates, and genetic control vascular patterning has been intensively characterized. In addition, many studies have been show environmental hormones and chemical compounds affect vascular growth. Natural marine compound GB9 was isolated from the marine soft coral Capnella imbricate, the study show GB9 had anti-neuroinflammatory and anti-nociceptive effects. However, the effect of GB9 on blood vessels is still unknown. In this study, we use transgene zebrafish as an animal model to understand the effect of vascular development in GB9 treated embryo. The results showed that GB9 treated embryos impair ISV (intersegmental vessel) growth, and CVP (caudal vein plexus) sprouting, which leads to pericardial edema and circulation defects. TUNEL assay and AO staining showed that vascular defects were not caused by apoptosis, but likely due to the impairment of cell proliferation and/or migration. We further showed GB9 treatment reduce cell proliferation marker p-HH3 and protein level, by counting p-HH3 immunostaining cell and Western blotting. In addition, we quantitated the migration distance of ISV between 24hpf and 28hpf and perform wound healing assay in endothelial cells EA.hy926. We show that GB9 treatment inhibits cell migration. Next, we examined the molecular mechanism of vascular defects by in situ hybridization, qPCR and Western blot, the results showed GB9 treatment decreases the expression of arteriovenous markers, ephrinb2, flt4, mrc1, flk and stabilinï¼›the protein levels related to VEGF, BMP signal pathways. Those results suggest that GB9 interfere vascular signaling regulation in zebrafish. Besides, we examine whether GB9 treatment cause vascular defect due to the increase of oxidative stress? We co-treated low-dose GB9 and H2O2, observed that defects in CVP formation was more severe than single treatment. Moreover, antioxidants Acetyl-cysteine (NAC) can rescue vascular defects in GB9 treated embryos. These data suggested that GB9 exposure causes vascular defects mediated by an increase in oxidative. Together our data show that GB9 treatment affect vascular development mediated by the interference of VEGF and BMP signals by the enhance of oxidative stress.
    Advisory Committee
  • ming-hong Tai - chair
  • Tzu-Fun Fu - co-chair
  • Zhi-Hong Wen - co-chair
  • Yung-Jen Chuang - co-chair
  • Chang-Yi Wu - advisor
  • Files
  • etd-0716117-115842.pdf
  • Indicate in-campus at 3 year and off-campus access at 3 year.
    Date of Submission 2017-08-17

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