Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells.
Recent reports, highlighting the relationships of cadmium exposure and vascular diseases, indicated that vascular endothelial cell was the target of cadmium (Cd) toxicity. However, the underlying mechanisms have not been fully elucidated. In this study, we evaluated the internalization of Cd2+ into human umbilical vein endothelial cells (HUVECs) by a novel Cd2+-selective sensor suitable for living cells. Then, we detected apoptosis in the treated cells. Our results showed that Cd2+ at low concentrations (< 10 micromol/l) inhibited apoptosis induced by deprivation of serum and basic fibroblast growth factor (bFGF). To investigate the corresponding molecular mechanisms, we employed acridine orange staining and Western blotting of MAP1 LC3 to detect autophagy, and analyzed the levels of integrin beta4, caveolin-1 and activity of PC-PLC. Our results showed that low concentrations of Cd2+ promoted autophagy and depressed the levels of integrin beta4, caveolin-1 and PC-PLC activity. The data suggested that autophagy played a key role in Cd2+ induced endothelial dysfunction; integrin beta4, caveolin-1 and PC-PLC might be the targets of Cd2+ in vascular endothelial cells.
Dong
Zhiwu
Z
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Wang
Li
L
Xu
Jiping
J
Li
Yulian
Y
Zhang
Yun
Y
Zhang
Shangli
S
Miao
Junying
J
D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D019187:Cadmium Compounds / Q000633:toxicity*; D051242:Caveolin 1 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D039642:Eukaryotic Initiation Factors / Q000378:metabolism; D006801:Humans; D020287:In Situ Nick-End Labeling; D009566:Nitrates / Q000633:toxicity*; D010738:Type C Phospholipases / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
C495540:CAV1 protein, human; D019187:Cadmium Compounds; D051242:Caveolin 1; C109284:EIF6 protein, human; D004785:Environmental Pollutants; D039642:Eukaryotic Initiation Factors; D009566:Nitrates; D010738:Type C Phospholipases; C105598:phosphatidylcholine-specific phospholipase C; C035196:cadmium nitrate