標題: Cholesterol loading augments oxidative stress in macrophages
作者: Hung, YC
Hong, MY
Huang, GS
材料科學與工程學系奈米科技碩博班
Graduate Program of Nanotechnology , Department of Materials Science and Engineering
關鍵字: low-density lipoproteins;foam cells;microarray;atherosclerosis;macrophages;oxidized LDL;acetylated LDL;apoptosis;expression pattern;inflammatory response;real-time RT-PCR
公開日期: 6-Feb-2006
摘要: To investigate the molecular consequence of loading free cholesterol into macrophages, we conducted a large-scale gene expression study to analyze acetylated-LDL-laden foam cells (AFC) and oxidized-LDL-laden foam cells (OFC) induced from human THP-1 cell lines. Cluster analysis was performed using 9600-gene microarray datasets from time course experiment. AFC and OFC shared common expression profiles; however, there were sufficient differences between these two treatments that AFC and OFC appealed as two separate entities. We identified 80 commonly upregulated genes and 48 commonly downregulated genes in AFC and OFC. Functional annotation of the differentially expressed genes indicated that apoptosis, extracellular matrix, oxidative stress, and cell proliferation was deregulated. We also identified 87 differentially expressed genes unique for AFC and 31 genes for OFC. The uniquely expressed genes of AFC are associated with kinase activity, ATP binding activity, and transporter activity, while unique genes for OFC are associated with cell signaling and adhesion. To validate the hypothesis that oxidative stress is a common feature for AFC and OFC, we performed a cluster analysis employing the genes related to oxidative stress, but we were unable to distinguish AFC from OFC in this manner. We performed real-time RTPCR and ELISA on foam cells to examine the transcripts and secreted protein of interleukin 1 beta (IL1 beta). IL1 beta was rapidly induced in foam cells, but for AFC both RNA level and protein level dropped immediately and was attenuated. To detect levels of reactive oxygen species in foam cells we conducted hydroethidine staining and observed high levels of superoxide anion. We conclude that loading free cholesterol induces high levels of superoxide anion, increases oxidative stress, and triggers a transient inflammatory response in macrophages. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
URI: http://dx.doi.org/10.1016/j.febslet.2005.12.102
http://hdl.handle.net/11536/12637
ISSN: 0014-5793
DOI: 10.1016/j.febslet.2005.12.102
期刊: FEBS LETTERS
Volume: 580
Issue: 3
起始頁: 849
結束頁: 861
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