Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells

Jer Chia Tsai, Hong Wang, Mark A. Perrella, Masao Yoshizumi, Nicholas E.S. Sibinga, Larissa C. Tan, Edgar Haber, Ted Hung Tse Chang, Robert Schlegel, Mu En Lee

Research output: Contribution to journalArticle

187 Scopus citations

Abstract

Homocysteine is an important and independent risk factor for arteriosclerosis. We showed previously that homocysteine stimulates vascular smooth muscle cell proliferation, a hallmark of arteriosclerosis. We show here that homocysteine and serum increased DNA synthesis synergistically in both human and rat aortic smooth muscle cells (RASMCs). Treatment of quiescent RASMCs with 1 mM homocysteine or 2% calf serum for 36 h increased cyclin A mRNA levels by 8- and 14-fold, respectively, whereas homocysteine plus serum increased cyclin A mRNA levels by 40-fold, indicating a synergistic induction of cyclin A mRNA. Homocysteine did not increase the half-life of cyclin A mRNA (2.9 h), but it did increase the transcriptional rate of the cyclin A gene in nuclear run-on experiments. The positive effect of homocysteine on cyclin A gene transcription was confirmed by our finding that homocysteine increased cyclin A promoter activity and ATF-binding protein levels in RASMCs. Finally, 1 mM homocysteine increased cyclin A protein levels and cyclin A-associated kinase activity by threefold. This homocysteine-induced expression of cyclin A may accelerate progression of arteriosclerotic lesions by promoting proliferation of vascular smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)146-153
Number of pages8
JournalJournal of Clinical Investigation
Volume97
Issue number1
DOIs
StatePublished - Jan 1 1996
Externally publishedYes

Keywords

  • atherosclerosis
  • cell cycle
  • gene regulation
  • myocardial infarction
  • transcription

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Tsai, J. C., Wang, H., Perrella, M. A., Yoshizumi, M., Sibinga, N. E. S., Tan, L. C., Haber, E., Chang, T. H. T., Schlegel, R., & Lee, M. E. (1996). Induction of cyclin A gene expression by homocysteine in vascular smooth muscle cells. Journal of Clinical Investigation, 97(1), 146-153. https://doi.org/10.1172/JCI118383