Homocysteine exerts cell type-specific inhibition of AP-1 transcription factor

Yuichiro J. Suzuki, Matthew V. Lorenzi, Susan S. Shi, Regina M. Day, Jeffrey B. Blumberg

Research output: Contribution to journalArticlepeer-review

19 Scopus citations


Homocysteine (Hcy) exerts either promoting or suppressive effects on mitogenesis in a cell type-specific manner. Hcy elicits proliferation of vascular smooth muscle cells, but is rather inhibitory to growth of endothelial cells and NIH/3T3 cells. In NIH/3T3 cells, we found that physiologically relevant concentrations (20-100 μM) of Hcy inhibit the activity of activating protein-1 (AP-1) transcription factor, although it is capable of eliciting immediate-early signaling events. Hcy induced p44/42 mitogen-activated protein kinase (MAPK) phosphorylation in control cells, but not in dominant negative p21(ras) transfected cells, indicating induction of the Ras-MAPK pathway. Hcy also induced the activity of serum response factor and expression of c-fos and c-jun genes. Despite the activation of these upstream events, Hcy potently inhibited AP-1 activity. Oxidized forms of Hcy (Hcy thiolactone, homocystine) were less effective in affecting AP-1. Hcy-mediated inhibition of AP-1 activity was not observed in A7r5 vascular smooth muscle cells. These results demonstrate that Hcy exerts cell type- and redox-specific inhibition of AP-1 dependent biological events. Copyright (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)39-45
Number of pages7
JournalFree Radical Biology and Medicine
Issue number1
StatePublished - Jan 2000


  • AP-1
  • Free radicals
  • Gene expression
  • Homocysteine
  • Redox
  • Signal transduction
  • Thiols

ASJC Scopus subject areas

  • Medicine(all)
  • Toxicology
  • Clinical Biochemistry


Dive into the research topics of 'Homocysteine exerts cell type-specific inhibition of AP-1 transcription factor'. Together they form a unique fingerprint.

Cite this