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J. Biol. Chem., Vol. 278, Issue 30, 28201-28209, July 25, 2003

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Redox Regulation of a Novel L1Md-A2 Retrotransposon in Vascular Smooth Muscle Cells^*

Kim P. Lu and Kenneth S. Ramos 

From the Center for Environmental and Rural Health, Texas A & M University, College Station, Texas 77843-4455

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.

Received for publication, April 14, 2003

^* This work was supported in part by National Institutes of Health Grants ES 04849 and ES 09106. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology and Center for Genetics and Molecular Medicine, University of Louisville Health Sciences Center, Louisville, KY 40292. Tel.: 502-852-5217; Fax: 502-852-6222; E-mail: kenneth.ramos{at}louisville.edu.

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