Identification of STC1 as an beta-amyloid activated gene in human brain microvascular endothelial cells using cDNA microarray.
To explore the molecular basis underlying beta-amyloid peptide (Abeta)-induced toxicity in the cerebrovasculature, we performed a cDNA microarray analysis to investigate the transcriptional profile induced by Abeta in human brain microvascular endothelial cells (HBMECs). This study identified 24 differentially expressed genes in HBMECs upon Abeta treatment. Among these genes, we found that the gene for a well-characterized calcium-regulating hormone, stanniocalcin-1 (STC1) was specifically up-regulated by Abeta treatment in a time and dose-dependent manner. Moreover, using overexpression and knock-down strategies, we found that overexpression of STC1 decreased transmigration of monocytes induced by Abeta and prevented Abeta-induced apoptosis of HBMECs. In addition, we explored the possible mechanisms underlying the effects of STC1, showing that overexpression of STC1 attenuated the effect of Abeta on up-regulating early growth response-1 (Egr-1), macrophage inflammatory protein-1beta (MIP-1beta), or cleaved caspase-8. Our data thus indicate a key role of STC1 in the response of HBMECs to Abeta exposure.
Li
Keshen
K
Department of Biomedical Engineering, Harbin Engineering University, Harbin 150001, China.
Dong
Daming
D
Yao
Lifen
L
Dai
Dawei
D
Gu
Xuefeng
X
Guo
Liang
L
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D017209:Apoptosis / Q000235:genetics; D001921:Brain / Q000098:blood supply* / Q000378:metabolism*; D002196:Capillaries / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D020869:Gene Expression Profiling; D006023:Glycoproteins / Q000235:genetics*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D015533:Transcriptional Activation
D016229:Amyloid beta-Peptides; D006023:Glycoproteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C051795:teleocalcin; D053181:Caspase 8