Safrole oxide induced human umbilical vein vascular endothelial cell differentiation into neuron-like cells by depressing the reactive oxygen species level at the low concentration.
Previously, we found that 5-25 microg/ml safrole oxide could inhibit apoptosis and dramatically make a morphological change in human umbilical vein vascular endothelial cells (HUVECs). But the possible mechanism by which safrole oxide function is unknown. To answer this question, in this study, we first investigated the effects of it on the activity of nitric oxide synthetase (NOS), the expressions of Fas and integrin beta4, which play important roles in HUVEC growth and apoptosis, respectively. The results showed that, at the low concentration (10 microg/ml), safrole oxide had no effects on NOS activity and the expressions of Fas and integrin beta4. Then, we investigated whether HUVECs underwent differentiation. We examined the expressions of neuron-specific enolase (NSE) and neurofilament-L (NF-L). Furthermore, we analyzed the changes of intracellular reactive oxygen species (ROS). After 10 h of treatment with 10 microg/ml safrole oxide, some HUVECs became neuron-like cells in morphology, and intensively displayed positive NSE and NF-L. Simultaneously, ROS levels dramatically decreased during HUVECs differentiation towards neuron-like cells. At the low concentration, safrole oxide induced HUVECs differentiation into neuron-like cells. Furthermore, our data suggested that safrole oxide might perform this function by depressing intracellular ROS levels instead of by affecting cell growth or apoptosis signal pathways.
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Le
L
Su
Jing
J
Zhao
Bao Xiang
BX
Zhao
Jun Ying
JY
Miao
De Ling
DL
Yin
Shang Li
SL
Zhang
D015153:Blotting, Western; D002352:Carrier Proteins / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects* / Q000502:physiology; D039642:Eukaryotic Initiation Factors; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012451:Safrole / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology*; D019014:fas Receptor / Q000378:metabolism
D002352:Carrier Proteins; C109284:EIF6 protein, human; D039642:Eukaryotic Initiation Factors; D007381:Intermediate Filament Proteins; D017382:Reactive Oxygen Species; D019014:fas Receptor; C009196:safrole oxide; D019001:Nitric Oxide Synthase; D012451:Safrole