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Publication : Mechanisms controlling competence gene expression in murine fibroblasts stimulated with minimally modified LDL.

First Author  Bork RW Year  1992
Journal  Arterioscler Thromb Volume  12
Issue  7 Pages  800-6
PubMed ID  1616905 Mgi Jnum  J:2193
Mgi Id  MGI:50717 Doi  10.1161/01.atv.12.7.800
Citation  Bork RW, et al. (1992) Mechanisms controlling competence gene expression in murine fibroblasts stimulated with minimally modified LDL. Arterioscler Thromb 12(7):800-6
abstractText  Mildly oxidized low density lipoprotein (minimally modified low density lipoprotein [MM-LDL] is capable of inducing gene expression in cells of the artery wall. In this study, we investigated the mechanisms that control the mRNA expression of JE, KC, c-myc, and c-fos in quiescent mouse L-cell fibroblasts stimulated with MM-LDL. The data demonstrate that MM-LDL induces increases greater than or equal to 20-fold in the levels of transcripts of these genes within 15-60 minutes. Of the four genes examined, JE and KC mRNA showed the greatest response to MM-LDL. The pattern of induction by MM-LDL is distinct from that observed in fibroblasts stimulated with serum, a known inducer of these genes. Treatment with cycloheximide (10 micrograms/ml) did not block the MM-LDL-induced increase in the mRNA levels of these genes. The increase of JE and KC mRNA levels in response to MM-LDL could be blocked by treatment with actinomycin D (5 micrograms/ml). In nuclear runoff studies, MM-LDL increased the transcription rate of JE and KC at 4 hours by 13-fold and fivefold, respectively. Small but reproducible stimulations of c-fos and c-myc transcription by MM-LDL were also observed. In addition, the half-life of JE mRNA was increased after addition of MM-LDL to fibroblasts, suggesting that the MM-LDL-induced accumulation of these mRNAs might be accomplished by both transcriptional and posttranscriptional mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)
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