Redox regulation of a novel L1Md-A2 retrotransposon in vascular smooth muscle cells.
Activation and reintegration of retrotransposons into the genome is linked to several diseases in human and rodents, but mechanisms of gene activation remain largely unknown. Here we identify a novel gene of L1Md-A2 lineage in vascular smooth muscle cells and show that environmental hydrocarbons enhance gene expression and activate monomer-driven transcription via a redox-sensitive mechanism. Site-directed mutagenesis and progressive deletion analyses identified two antioxidant/electrophile response-like elements (5'-GTGACTCGAGC-3') within the A2/3 and A3 region. These elements mediated activation, with the A3 monomer playing an essential role in transactivation. This signaling pathway may contribute to gene instability during the course of atherogenesis.
Lu
Kim P
KP
Center for Environmental and Rural Health, Texas A & M University, College Station, Texas 77843-4455, USA.
Ramos
Kenneth S
KS
D000818:Animals; D001011:Aorta / Q000166:cytology; D001483:Base Sequence; D002478:Cells, Cultured; D004251:DNA Transposable Elements; D004730:Endothelium, Vascular / Q000378:metabolism*; D017353:Gene Deletion; D005822:Genetic Vectors; D006838:Hydrocarbons / Q000737:chemistry; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009130:Muscle, Smooth / Q000166:cytology*; D016297:Mutagenesis, Site-Directed; D016366:Open Reading Frames; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010957:Plasmids / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D015398:Signal Transduction; D014018:Tissue Distribution; D015533:Transcriptional Activation; D014162:Transfection
D004251:DNA Transposable Elements; D006838:Hydrocarbons; D008156:Luciferases