ADVERTISEMENT
ADVERTISEMENT

Diabetic vascular damage

Inhibition of PARP may block hyperglycemia-induced vascular damage

Tudor Toma(t.toma@imperial.ac.uk)

Hyperglycemia is important in the pathogenesis of diabetic vascular disease, and the four major molecular mechanisms implicated in hyperglycemia-induced vascular damage reflect a single process: overproduction of superoxide by the mitochondrial electron transport chain. However, the precise pathway by which overproduction of superoxide induces vascular damage has been unclear. In the October 1 Journal of Clinical Investigation, Xueliang Du and colleagues at the Albert Einstein College of Medicine, show that inhibition of GAPDH activity by poly(ADP-ribose) polymerase (PARP) activates three major pathways of hyperglycemic damage in endothelial cells (Journal of Clinical Investigation, 112:1049–1057, October 1, 2003).

Du et al. performed in vitro experiments on bovine aortic endothelial cells and observed that hyperglycemia-induced GAPDH inhibition was a consequence of poly(ADP-ribosyl)ation of GAPDH by PARP—activated by DNA strand breaks produced by mitochondrial superoxide overproduction. In addition, the authors showed that blocking PARP activity with the competitive PARP inhibitors...

Interested in reading more?

Become a Member of

Receive full access to more than 35 years of archives, as well as TS Digest, digital editions of The Scientist, feature stories, and much more!
Already a member?
ADVERTISEMENT