Homocysteine as a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide
Article first published online: 5 FEB 2009
1997 British Pharmacological Society
British Journal of Pharmacology
Volume 122, Issue 2, pages 269–274, September 1997
How to Cite
Nishio, E. and Watanabe, Y. (1997), Homocysteine as a modulator of platelet-derived growth factor action in vascular smooth muscle cells: a possible role for hydrogen peroxide. British Journal of Pharmacology, 122: 269–274. doi: 10.1038/sj.bjp.0701391
- Issue published online: 5 FEB 2009
- Article first published online: 5 FEB 2009
- (Received March 3, 1997, Revised June 19, 1997, Accepted June 20, 1997)
- platelet derived growth factor-BB;
- superoxide dismutase;
- glutathione peroxidase;
- vascular smooth muscle cell;
- 1Homocysteine is an independent risk factor for cardiovascular disease. The mechanisms by which elevated plasma concentrations of homocysteine are related to the pathogenesis of atherosclerosis are not fully understood. Therefore, we examined the effect of homocysteine on cell replication of rat cultured vascular smooth muscle cells (VSMCs) at concentrations similar to those observed in clinical studies.
- 2The incorporation of [3H]-thymidine was used as a marker of mitosis. Homocysteine (250–500 μM) was a weak mitogen as compared to platelet-derived growth factor-BB (PDGF-BB, 1 nM) and serum (10%), but it potentiated the mitogenic effect of PDGF-BB four fold at 500 μM. This enhancement of mitogenesis was blunted by the addition of the scavenging enzyme catalase or the antioxidant N-acetyl-L-cysteine.
- 3Furthermore, stimulation of VSMC with homocysteine (25–500 μM) decreased the glutathione peroxidase activity of the cells to 50% of control at 500 μM. Inversely, homocysteine enhanced the superoxide dismutase (SOD) activity to 137% of control at 500 μM, but it had no effect on the catalase activity.
- 4Homocysteine decreased the activity of bovine purified liver cytosolic glutathione peroxidase in a time- and dose-dependent manner. The maximum decrease was 50%.
- 5In summary, homocysteine has a weak mitogenic effect on VSMC, but it dramatically enhances the mitogenic response of PDGF-BB, presumably by disturbing the activity of antioxidant enzymes.
British Journal of Pharmacology (1997) 122, 269–274; doi:10.1038/sj.bjp.0701391