Peroxisome proliferator-activated receptor ???? ligands activate transcription of lectin-like oxidized low density lipoprotein receptor-1 gene through GC box motif

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• 作者：Hayashida ; Kazutaka ; Kume ; Noriaki ; Minami ; Manabu ; Inui-Hayashida ; Atsuko ; Mukai ; Eri ; Toyohara ; Masako ; et. al.
• 关键词：Lectin-like oxidized low-density lipoprotein receptor-1 ; Peroxisome proliferators-activated receptors ???? ; Vascular endothelial cells ; GC box like motif ; Oxidized LDL
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2004
• 出版时间：October 22, 2004
• 年：2004
• 卷：323
• 期：3
• 页码：1116-1123
• 全文大小：3.09 M

文摘

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is a receptor for oxidized LDL. Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors regulating transcription of various genes. We examined effects of PPAR ligands on LOX-1 expression and their transcriptional regulation in vascular endothelial cells. PPAR??-specific ligands, such as fenofibrate and WY-14643, but not PPAR??-specific ligands induced LOX-1 expression. Reduced expression of PPAR?? by antisense oligonucleotides directed to PPAR?? blocked fenofibrate-induced LOX-1 expression. Luciferase reporter gene assays with deletion and point mutations in the LOX-1 promoter revealed that transcriptional activity of LOX-1 gene by fenofibrate was localized in the ???114/???106 GC box. Electrophoretic mobility shift assays with the radiolabeled GC box sequence showed inducible bands by PPAR?? ligands, which is competitively suppressed by unlabeled GC box motif and by an antibody to PPAR??. In conclusion, PPAR?? appears to be one of the key regulators that induce LOX-1 expression, utilizing the GC box as a promoter.