Abstract
The disrupted metabolism of homocysteine (Hcy) causes hyperhomocysteinemia, a condition associated with the impairment of nitric oxide (NO) bio-availability, tissue hypoxia and increased risk of vascular disease. Here, we examined how Hcy modulates the induction of the stress protein haem oxygenase-1 (HO-1) evoked by NO releasing agents and hypoxia in vascular endothelial cells. We found that Hcy (0.5 mM) markedly reduced the increase in haem oxygenase activity and HO-1 protein expression induced by sodium nitroprusside (SNP, 0.5 mM) but did not affect HO-1 activation mediated by S-nitroso-N-acetyl-penicillamine. Cells pre-treated with Hcy followed by addition of fresh medium containing SNP still exhibited an augmented haem oxygenase activity. Interestingly, high levels of Hcy were also able to abolish hypoxia-mediated HO-1 expression in a concentration-dependent manner. These novel findings indicate that hyperhomocysteinemia interferes with crucial signaling pathways required by cells to respond and adapt to stressful conditions.
| Original language | English |
|---|---|
| Pages (from-to) | 403-6 |
| Number of pages | 4 |
| Journal | FEBS Letters |
| Volume | 508 |
| Issue number | 3 |
| Publication status | Published - 23 Nov 2001 |
Keywords
- Animals
- Cattle
- Cell Hypoxia
- Cells, Cultured
- Culture Media
- Dose-Response Relationship, Drug
- Endothelium, Vascular
- Enzyme Induction
- Heme Oxygenase (Decyclizing)
- Homocysteine
- Nitric Oxide
- Nitric Oxide Donors
- Nitroprusside
- S-Nitroso-N-Acetylpenicillamine
- Journal Article
- Research Support, Non-U.S. Gov't