Malachite green induces cardiovascular defects in developing zebrafish (Danio rerio) embryos by blocking VEGFR-2 signaling.
Malachite green (MG) is a triphenyl methane dye used in various fields that demonstrates high toxicity to bacteria and mammalian cells. When bud stage zebrafish embryos were treated with MG at 125, 150, and 175ppb for 14h, the development of trunk including intersomitic vessels was inhibited in MG-treated flk-1-GFP transgenic embyos. MG clearly induced whole growth retardation. MG induced severe cell death in trunk intersomite region of zebrafish embryos and in human vascular endothelial cells in a dose-dependent manner. MG inhibited heart rates and cardiac looping. MG attenuated whole blood formation and inhibited vascular endothelial growth factor (VEGF)-induced receptor (R)-2 phosphorylation in vascular endothelial cells. In conclusion, MG significantly alters the cardiovascular development causing growth retardation in zebrafish through the blocking VEGFR-2 activation in early cardiovascular development. It suggests that MG may be an environmental toxic agent with the potential to induce embryonic cardiovascular defects in vertebrates.
Department of Natural Sciences, School of Life Sciences and Biotechnology, Kyungpook National University, Daegu 702-701, Republic of Korea.
Gun Hyuk
GH
Jang
In-Sook
IS
Park
Sun Hee
SH
Lee
Tae-Lin
TL
Huh
You Mie
YM
Lee
D000818:Animals; D017209:Apoptosis; D001919:Bradycardia / Q000139:chemically induced; D018376:Cardiovascular Abnormalities / Q000139:chemically induced* / Q000201:enzymology; D002478:Cells, Cultured; D004396:Coloring Agents / Q000633:toxicity*; D004625:Embryo, Nonmammalian / Q000002:abnormalities / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000002:abnormalities / Q000187:drug effects / Q000201:enzymology; D005659:Fungicides, Industrial / Q000633:toxicity*; D006410:Hematopoiesis / Q000187:drug effects; D006801:Humans; D018919:Neovascularization, Physiologic; D010766:Phosphorylation / Q000187:drug effects; D012394:Rosaniline Dyes / Q000633:toxicity*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015027:Zebrafish / Q000002:abnormalities*
D004396:Coloring Agents; D005659:Fungicides, Industrial; D012394:Rosaniline Dyes; C005095:malachite green; D040301:Vascular Endothelial Growth Factor Receptor-2