碩士 / 國立中山大學 / 生物科學系研究所 / 104 / The balance of reduction-oxidation (redox) has been shown acting an important role in vascular formation, especially in angiogenesis. Most studies have done in adult animals under pathological conditions, and very limited information about oxidative stress and vascular development during embryogenesis. Here, we report a novel biologi-cal function of prdx1 that play critical roles in vascular growth during zebrafish devel-opment.
Prdx1 (peroxiredoxin1) belongs to a member of the peroxiredoxin family of anti-oxidant enzymes.We show prdx1 is expressed in developing vessels and knockdown of prdx1 by morpholino injection impairs the growth of ISV (intersegmental vessel) and CVP (cardinal vein plexus), suggesting the role of prdx1 in promoting vessels growth. We further show the reduction of ISV cells is due to a decrease of cell proliferation and migration, but not results from cell death in non-endothelial cells.
The molecular evidence of vascular defects in prdx1MO is related to the decreased ex-pression of vascular markers, flt4, mrc1, stabilin and ephrinb2. Loss of prdx1 results in vascular defects suggest the antioxidant function is important, thus, we tested if oxida-tive stress could cause vascular defects in H2O2-treated embryos. Our data showed H2O2 treatment impaired CVP formation and caused mild ISV defects. While H2O2-treated embryo combined with knockdown of prdx1, synergetic effects are ob-served. In addition, exogenous N-acetylcysteine (NAC) treatment rescues the vascular defects in prdx1MO. These data suggest the oxidative stress indeed can disturb vascular development. We further show the differential regulation of antioxidant genes SOD1, SOD2 and catalase in prdx1morphants from H2O2-treated embryos.
To confirm the role of prdx1 in vasculature, we overexpressed prdx1 in the embryos and found overexpression of prdx1 promotes ISV and CVP growth. Meanwhile, overexpres-sion of prdx1 can rescue the loss of prdx1. These data suggest prdx1 functions in vascu-lar development necessary and sufficient. Interestingly, we found the increased expres-sion of blood markers (gata1, globin) coincident with the decreased expression of en-dothelial markers flk1 and fli1a in prdx1 MO, suggested prdx1 likely regulate hemangio-blast fate decision at earlier developmental stage. We further demonstrate prdx1 likely interacts with Notch to control cell fate switch and regulated by BMP and VEGF sig-nals. Together, we showed prdx1 play novel and critical roles in vascular growth during zebrafish development.
| Identifer | oai:union.ndltd.org:TW/104NSYS5112034 |
| Date | January 2016 |
| Creators | Po-Chun Huang, 黃柏鈞 |
| Contributors | Chang-Yi Wu, 吳長益 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 74 |
Page generated in 0.0019 seconds