Glycated serum albumin-induced nitric oxide production in vascular smooth muscle cells by nuclear factor κB-dependent transcriptional activation of inducible nitric oxide synthase Academic Article uri icon

Overview

MeSH Major

  • Muscle, Smooth, Vascular
  • NF-kappa B
  • Nitric Oxide
  • Nitric Oxide Synthase
  • Serum Albumin

abstract

  • Glycated proteins, including serum albumin, may be involved in the pathogenesis of diabetic vasculopathy. Recent evidence suggests that expression of inducible nitric oxide synthase (iNOS) in vascular smooth muscle cells (VSMC) may, in part, promote atherosclerosis by increasing local oxidative stress. We therefore investigated whether VSMC exposed to glycated human serum albumin (GHSA) produce nitric oxide (NO) by increasing iNOS expression through transcriptional activation of the iNOS gene and whether this process is dependent on nuclear factor kappaB (NF-kappaB) activation. Treatment of VSMC with GHSA causes activation of NF-kappaB and the iNOS promoter. Induction of NF-kappaB and the iNOS promoter by GHSA exhibited dose-dependent kinetics at concentrations ranging from 3 to 1000 microgram/ml. GHSA alone was a weak inducer of NO production in VSMC as measured by determining nitrite levels, and interferon-gamma alone was totally ineffective, whereas the combination of GHSA and interferon-gamma was a strong stimulus. This synergy for NO production corresponded to Northern blot analyses of iNOS mRNA expression. Thus, GHSA may promote atherosclerosis in part by activation of NF-kappaB and upregulation of iNOS, thereby fostering local inflammation and oxidative stress.

publication date

  • May 27, 1999

Research

keywords

  • Academic Article

Identity

Language

  • eng

Digital Object Identifier (DOI)

  • 10.1006/bbrc.1999.0736

PubMed ID

  • 10334927

Additional Document Info

start page

  • 128

end page

  • 32

volume

  • 259

number

  • 1