Hyperglycemia reduces nitric oxide synthase and glycogen synthase activity in endothelial cells

I. Noyman, M. Marikovsky, S. Sasson, A. H. Stark, K. Bernath, R. Seger, Z. Madar*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

47 Scopus citations

Abstract

Hyperglycemia is considered a primary cause of diabetic vascular complications. A hallmark of vascular disease is endothelial cell dysfunction characterized by diminished nitric-oxide (NO)-dependent phenomena such as vasodilation, angiogenesis, and vascular maintenance. This study was designed to investigate the effects of a high level of D-glucose on endothelial NO response, oxidative stress, and glucose metabolism. Bovine aortic endothelial cells (BAECs) were pretreated with a high concentration of glucose (HG) (22 mmol/L) for at least 2 weeks and compared with control cells exposed to 5 mmol/L glucose (NG). The effect of chronic hyperglycemia on endothelial NO-synthase (eNOS) activity and expression, glycogen synthase (GS) activity, extracellular-signal-regulated kinase (ERK 1,2), p38, Akt expression, and Cu/Zn superoxide-dismutse (SOD-1) activity and expression were determined. Western blot analysis showed that eNOS protein expression decreased in HG cells and was accompanied by diminished eNOS activity. The activity of GS was also significantly lower in the HG cells than in NG cells, 25.0 ± 17:4 and 89 ± 22.5 nmol UDP-glucose·mg protein-1 × min-1, respectively. Western blot analysis revealed a 40-60% decrease in ERK 1,2 and p38 protein levels, small modification of phosphorylated Akt expression, and a 30% increase in SOD-1 protein expression in HG cells. Although SOD expression was increased, no change was observed in SOD activity. These results support the findings that vascular dysfunction due to exposure to pathologically high D-glucose concentrations may be caused by impairment of the NO pathway and increased oxidative stress accompanied by altered glucose metabolism.

Original languageAmerican English
Pages (from-to)187-193
Number of pages7
JournalNitric Oxide - Biology and Chemistry
Volume7
Issue number3
DOIs
StatePublished - 2002

Keywords

  • Cu/Zn superoxide dismutase
  • ERK1,2, p38
  • Endothelial cells
  • Glycogen synthase
  • Hyperglycemia
  • Nitric oxide

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