A novel isochroman derivative inhibited apoptosis in vascular endothelial cells through depressing the levels of integrin beta4, p53 and ROS.
A new derivative of isochroman, 7-(isopropoxymethyl)-5-phenyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isochromene (ISO-9), was synthesized in our laboratory. In this study, we investigated the effect of ISO-9 on the apoptosis induced by deprivation of serum and fibroblast growth factor-2 (FGF-2) in human umbilical vein vascular endothelial cells (HUVECs). The results of MTT assay showed that 40 microM ISO-9 prevented the reduction of cell viability induced by the deprivation of serum and FGF-2 at 24 h or 48 h, respectively. To further study the correlated mechanism, the levels of integrin beta4, p53 and reactive oxygen species (ROS) were analyzed. The results showed that the high levels of integrin beta4, p53 and ROS induced by the deprivation of serum and FGF-2 could be inhibited by the treatment of 40 microM ISO-9. The data suggested that ISO-9 was a promising anti-apoptotic agent and could be served as a useful tool to study the molecular mechanism of apoptosis in vascular endothelial cells (VECs).
Zhang
Lu
L
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Zhu
Xingshang
X
Zhao
BaoXiang
B
Zhao
Jing
J
Zhang
Yun
Y
Zhang
ShangLi
S
Miao
JunYing
J
D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044967:Serum / Q000378:metabolism; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C530273:7-(isopropoxymethyl)-5-phenyl-7,8-dihydro-5H-(1,3)dioxolo(4,5-g)isochromene; D052117:Benzodioxoles; D001578:Benzopyrans; D039663:Integrin beta4; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016222:Fibroblast Growth Factor 2