TY - JOUR
T1 - Autoxidation products of both carbohydrates and lipids are increased in uremic plasma
T2 - Is there oxidative stress in uremia?
AU - Miyata, Toshio
AU - Fu, Min Xin
AU - Kurokawa, Kiyoshi
AU - Van Ypersele De Strihou, Charles
AU - Thorpe, Suzanne R.
AU - Baynes, John W.
N1 - Funding Information:
This study was supported by Research for the Future Program of the Japan Society for the Promotion of Science grant (96L00303) to TM, United States Public Health Service grants (NIDDK 19971) to JWB and (AG11472, P01-HL55782) to SRT, and a Juvenile Diabetes Foundation International grant to SRT.
PY - 1998
Y1 - 1998
N2 - Background. Advanced glycation end products (AGEs), formed by non- enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. Methods. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. Results. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (F < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). Conclusions. These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.
AB - Background. Advanced glycation end products (AGEs), formed by non- enzymatic glycation and oxidation (glycoxidation) reactions, have been implicated in the pathogenesis of several diseases, including normoglycemic uremia. AGE research in uremia has focused on the accumulation of carbohydrate-derived adducts generated by the Maillard reaction. Recent studies, however, have demonstrated that one AGE, the glycoxidation product carboxymethyllysine (CML), could be derived not only from carbohydrates but also from oxidation of polyunsaturated fatty acids in vitro, raising the possibility that both carbohydrate and lipid autoxidation might be increased in uremia. Methods. To address this hypothesis, we applied gas chromatography-mass spectrometry and high performance liquid chromatography to measure protein adducts formed in uremic plasma by reactions between carbonyl compounds and protein amino groups: pentosidine derived from carbohydrate-derived carbonyls, malondialdehyde (MDA)-lysine derived from lipid-derived carbonyls, and CML originating possibly from both sources. Results. All three adducts were elevated in uremic plasma. Plasma CML levels were mainly (>95%) albumin bound. Their levels were not correlated with fructoselysine levels and were similar in diabetic and non-diabetic patients on hemodialysis, indicating that their increase was not driven by glucose. Pentosidine and MDA-lysine were also increased in plasma to the same extent in diabetic and non-diabetic hemodialysis patients. Statistical analysis indicated that plasma levels of CML correlated weakly (F < 0.05) with those of pentosidine and MDA-lysine, but that pentosidine and MDA-lysine varied independently (P > 0.5). Conclusions. These data suggest that the increased levels of AGEs in blood, and probably in tissues, reported in uremia implicate a broad derangement in non-enzymatic biochemistry involving alterations in autoxidation of both carbohydrates and lipids.
KW - AGEs
KW - Carboxymethyllysine
KW - Glycoxidation
KW - Lipoxidation
KW - Malondialdehyde- lysine
KW - Non-enzymatic biochemistry
KW - Oxidative protein damage
KW - Pentosidine
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U2 - 10.1046/j.1523-1755.1998.00093.x
DO - 10.1046/j.1523-1755.1998.00093.x
M3 - Article
C2 - 9767546
AN - SCOPUS:0031656155
SN - 0085-2538
VL - 54
SP - 1290
EP - 1295
JO - Kidney International
JF - Kidney International
IS - 4
ER -
