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标题：Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 5'-phosphate as the inhibitor
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作者：Higuchi, Ohki ; Nakagawa, Kiyotaka ; Tsuzuki, Tsuyoshi 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2006
卷号：47
期号：5
页码：964-974
DOI：10.1194/jlr.M500348-JLR200
出版社：American Society for Biochemistry and Molecular Biology
摘要：Peroxidized phospholipid-mediated cytotoxity is involved inthe pathophysiology of a number of diseases [i.e., the abnormalincrease of phosphatidylcholine hydroperoxide (PCOOH) foundin the plasma of type 2 diabetic patients]. The PCOOH accumulationmay relate to Amadori-glycated phosphatidylethanolamine (deoxy-D-fructosylPE, or Amadori-PE), because Amadori-PE causes oxidative stress.However, lipid glycation inhibitor has not been discovered yetbecause of the lack of a lipid glycation model useful for inhibitorscreening. We optimized and developed a lipid glycation modelconsidering various reaction conditions (glucose concentration,temperature, buffer type, and pH) between PE and glucose. Usingthe developed model, various protein glycation inhibitors (aminoguanidine,pyridoxamine, and carnosine), antioxidants (ascorbic acid, ${alpha}$ -tocopherol,quercetin, and rutin), and other food compounds (L-lysine, L-cysteine,pyridoxine, pyridoxal, and pyridoxal 5'-phosphate) were evaluatedfor their antiglycative properties. Pyridoxal 5'-phosphate andpyridoxal (vitamin B₆ derivatives) were the most effective antiglycativecompounds. These pyridoxals could easily be condensed with PEbefore the glucose/PE reaction occurred. Because PE-pyridoxal5'-phosphate adduct was detectable in human red blood cellsand the increased plasma Amadori-PE concentration in streptozotocin-induceddiabetic rats was decreased by dietary supplementation of pyridoxal5'-phosphate, it is likely that pyridoxal 5'-phosphate actsas a lipid glycation inhibitor in vivo, which possibly contributesto diabetes prevention. Supplementary key words lipid glycation inhibitor • phosphatidylethanolamine • diabetes Abbreviations: AGE, advanced glycation end product; dioleoyl-PE, 1,2-di(cis-9-octadecenoyl)-sn-glycero-3-phosphoethanolamine; ELSD, evaporative light-scattering detection; LC, liquid chromatography; MRM, multiple reaction monitoring; MS, mass spectrometry; PCOOH, phosphatidylcholine hydroperoxide; PE, phosphatidylethanolamine; QTRAP LC/MS/MS, quadrupole/linear ion-trap liquid chromatography tandem mass spectrometry; RBC, red blood cell; STZ; streptozotocin