Effect of reactive oxygen and carbonyl species on crucial cellular antioxidant enzymes

Chem Biol Interact. 2011 Mar 15;190(1):28-34. doi: 10.1016/j.cbi.2010.12.028. Epub 2011 Jan 7.

Abstract

Numerous reactive oxygen species (ROS) and reactive carbonyl species (RCS) issuing from lipid and sugar oxidation are known to damage a large number of proteins leading to enzyme inhibition and alteration of cellular functions. Whereas studies in literature only focus on the reactivity of one or two of these compounds, we aimed at comparing in the same conditions of incubations (4 and 24h at 37°C) the effects of both various RCS (4-hydroxynonenal, 4-hydroxyhexenal, acrolein, methylglyoxal, glyoxal, malondialdehyde) and ROS (H₂O₂, AAPH) on the activity of key enzymes involved in cellular oxidative stress: superoxide dismutase (Cu,Zn-SOD), glutathione peroxidase (GPx), glutathione S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH). This was realized both in vitro on purified proteins and MIAPaCa-2 cells. Incubation of these enzymes with RCS resulted in a significant time- and concentration-dependent inhibition for both pure enzymes and in cell lysates. Among all RCS and ROS, hydroxynonenal (HNE) was observed as the most toxic for all studied enzymes except for SOD and is followed by hydrogen peroxide. At 100μM, HNE resulted in a 50% reduction of GPx, 56% of GST, 65% of G6PDH, and only 10% of Cu,Zn-SOD. Meanwhile it seems that concentrations used in our study are closer to biological conditions for ROS than for RCS. H₂O₂ and AAPH-induced peroxyl radicals may be probably more toxic towards the studied enzymes in vivo.

MeSH terms

  • Acrolein / toxicity
  • Aldehydes / toxicity*
  • Amidines / toxicity
  • Antioxidants / metabolism*
  • Cell Line, Tumor
  • Glucosephosphate Dehydrogenase / metabolism
  • Glutathione Peroxidase / metabolism
  • Glutathione Transferase / metabolism*
  • Glyoxal / toxicity
  • Humans
  • Hydrogen Peroxide / toxicity
  • Malondialdehyde / toxicity
  • Oxidative Stress*
  • Oxidoreductases / metabolism*
  • Pyruvaldehyde / toxicity
  • Reactive Oxygen Species / toxicity*
  • Superoxide Dismutase / metabolism

Substances

  • Aldehydes
  • Amidines
  • Antioxidants
  • Reactive Oxygen Species
  • 4-hydroxyhexenal
  • Malondialdehyde
  • Glyoxal
  • Pyruvaldehyde
  • 2,2'-azobis(2-amidinopropane)
  • Acrolein
  • Hydrogen Peroxide
  • Oxidoreductases
  • Glucosephosphate Dehydrogenase
  • Glutathione Peroxidase
  • Superoxide Dismutase
  • Glutathione Transferase
  • 4-hydroxy-2-nonenal