TY - JOUR
T1 - Anaerobic vs aerobic pathways of carbonyl and oxidant stress in human lens and skin during aging and in diabetes
T2 - A comparative analysis
AU - Fan, Xingjun
AU - Sell, David R.
AU - Zhang, Jianye
AU - Nemet, Ina
AU - Theves, Mathilde
AU - Lu, Jie
AU - Strauch, Christopher
AU - Halushka, Marc K.
AU - Monnier, Vincent M.
N1 - Funding Information:
This work was supported by NEI Grant EY07099 to V.M.M., American Diabetes Association Grant 1-05-JF-20 to M.K.H., and NIDDK Grant DK079432 to D.R.S.
PY - 2010/9
Y1 - 2010/9
N2 - The effects of anaerobic (lens) vs aerobic (skin) environment on carbonyl and oxidant stress are compared using de novo and existing data on advanced glycation and oxidation products in human crystallins and collagen. Almost all modifications increase with age. Methylglyoxal hydroimidazolones, carboxymethyllysine, and carboxyethyllysine are severalfold higher in lens than in skin and markedly increase upon incubation of lens crystallins with 5mM ascorbic acid. In contrast, fructose-lysine, glucosepane crosslinks, glyoxal hydroimidazolones, metal-catalyzed oxidation (allysine), and H2O2-dependent modifications (2-aminoapidic acid and methionine sulfoxide) are markedly elevated in skin, but relatively suppressed in the aging lens. In both tissues ornithine is the dominant modification, implicating arginine residues as the principal target of the Maillard reaction in vivo. Diabetes (here mostly type 2 studied) increases significantly fructose-lysine and glucosepane in both tissues (P<0.001) but has surprisingly little effect on the absolute level of most other advanced glycation end products. However, diabetes strengthens the Spearman correlation coefficients for age-related accumulation of hydrogen peroxide-mediated modifications in the lens. Overall, the data suggest that oxoaldehyde stress involving methylglyoxal from either glucose or ascorbate is predominant in the aging noncataractous lens, whereas aging skin collagen undergoes combined attack by nonoxidative glucose-mediated modifications, as well as those from metal-catalyzed oxidation and H2O2.
AB - The effects of anaerobic (lens) vs aerobic (skin) environment on carbonyl and oxidant stress are compared using de novo and existing data on advanced glycation and oxidation products in human crystallins and collagen. Almost all modifications increase with age. Methylglyoxal hydroimidazolones, carboxymethyllysine, and carboxyethyllysine are severalfold higher in lens than in skin and markedly increase upon incubation of lens crystallins with 5mM ascorbic acid. In contrast, fructose-lysine, glucosepane crosslinks, glyoxal hydroimidazolones, metal-catalyzed oxidation (allysine), and H2O2-dependent modifications (2-aminoapidic acid and methionine sulfoxide) are markedly elevated in skin, but relatively suppressed in the aging lens. In both tissues ornithine is the dominant modification, implicating arginine residues as the principal target of the Maillard reaction in vivo. Diabetes (here mostly type 2 studied) increases significantly fructose-lysine and glucosepane in both tissues (P<0.001) but has surprisingly little effect on the absolute level of most other advanced glycation end products. However, diabetes strengthens the Spearman correlation coefficients for age-related accumulation of hydrogen peroxide-mediated modifications in the lens. Overall, the data suggest that oxoaldehyde stress involving methylglyoxal from either glucose or ascorbate is predominant in the aging noncataractous lens, whereas aging skin collagen undergoes combined attack by nonoxidative glucose-mediated modifications, as well as those from metal-catalyzed oxidation and H2O2.
KW - Collagen
KW - Crystallins
KW - Free radicals
KW - Glycation
KW - Metals
KW - Methylglyoxal
KW - Oxidative stress
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U2 - 10.1016/j.freeradbiomed.2010.06.003
DO - 10.1016/j.freeradbiomed.2010.06.003
M3 - Article
C2 - 20541005
AN - SCOPUS:77955095090
SN - 0891-5849
VL - 49
SP - 847
EP - 856
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 5
ER -