Free radical generation by early glycation products: A mechanism for accelerated atherogenesis in diabetes

https://doi.org/10.1016/S0006-291X(05)80875-7Get rights and content

Abstract

Non-enzymatic glycation of reactive amino groups in model proteins increased the rate of free radical production at physiologic pH by nearly fifty-fold over non-glycated protein. Superoxide generation was confirmed by electron paramagnetic resonance measurements with the spin-trap phenyl-t-butyl-nitrone. Both Schiff base and Amadori glycation products were found to generate free radicals in a ratio of 1:1.5. Free radicals generated by glycated protein increased peroxidation of membranes of linoleic/arachidonic acid vesicles nearly 2-fold over control, suggesting that the increased glycation of proteins in diabetes may accelerate vascular wall lipid oxidative modification.

References (36)

  • KawateR. et al.

    Adv. Metab. Dis.

    (1978)
  • SparrowC.P. et al.

    J. Biol. Chem

    (1989)
  • BeauchampC. et al.

    Anal. Biochem.

    (1971)
  • MottleyC. et al.

    Biochem. Biophys. Res. Comm.

    (1986)
  • GebickiJ.M. et al.

    Chem. and Phys. Lipids

    (1976)
  • AhmedM.U. et al.

    J. Biol. Chem.

    (1986)
  • GutteridgeJ.M.C. et al.

    Biochim. Biophys. Acta

    (1983)
  • AraiK. et al.

    Biochim. Biophys. Acta

    (1987)
  • AraiK. et al.

    J. Biol. Chem.

    (1987)
  • ColwellJ.A. et al.

    Diabetes Care

    (1989)
  • WilsonP.W.F. et al.

    Dyslipoproteinemias and diabetes

  • WelbornT.A. et al.

    Diabetes Care

    (1979)
  • JarettR.J.

    Diabetologia

    (1988)
  • WestK.

    Epidemiology of Diabetes and Its Vascular Lesions

  • SteinbergD. et al.

    N. Engl. J. Med.

    (1989)
  • QuinnM.T. et al.
  • MorelD.W. et al.

    J. Clin. Invest

    (1984)
  • HaberlandM.E. et al.

    Science

    (1988)
  • Cited by (0)

    View full text