Identification of a novel advanced glycation end product derived from lactaldehyde
Identification of a novel advanced glycation end product derived from lactaldehyde
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DOI：
10.1080/09168451.2019.1585745
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发表时间：
2019-06-03
影响因子：
1.6
通讯作者：
Watanabe, Hirohito
中科院分区：
文献类型：
--
作者：
Fujimoto, Shiori;Murakami, Yoto;Watanabe, Hirohito
晚期糖基化终产物（AGEs）通过AGEs受体（AGEs）参与糖尿病并发症的发展。我们已经报道，3-羟基吡啶鎓（3 HP）含有AGEs来自-羟基醛物理相互作用的干扰素，并显示细胞毒性。乳酸醛（LA）是由苏氨酸和髓过氧化物酶之间的反应形成的，但没有LA衍生的AGEs已被表征。在这里，我们确定的结构和生理作用的年龄来自LA。从乳酸和N-乙酰基-L-赖氨酸的混合物中分离得到一种新的3 HP衍生物2-乙酰氨基-6-（3-羟基-5-甲基-吡啶-1-鎓-1-基）己酸酯，命名为N-乙酰基-LAPL（lactaldehyde-derived pyridinium-type lysine addition）。在LA修饰的蛋白中也检测到LAPL。LAPL在PC 12神经元细胞中引起毒性，但该作用被可溶性形式的作为诱饵受体的LPL抑制。此外，基于表面等离子体共振的分析显示，LAPL特异性结合重组的p53。缩略语：AGEs：晚期糖基化终产物; AGEs：晚期糖基化终产物受体; 3 HP：3-羟基吡啶鎓; LA：乳醛; LAPL：乳醛衍生的吡啶鎓型赖氨酸加合物; BSA：牛血清白蛋白;甘氨酰甘油衍生的吡啶鎓; MPO：髓过氧化物酶; HFBA：七氟丁酸; TFA：三氟乙酸; HPLC：高效液相色谱; LC-ESI-QTOF-MS：液相色谱-电喷雾电离-四极杆飞行时间-质谱; NMR：核磁共振; LA-BSA：乳醛修饰的牛血清白蛋白; PBS：磷酸盐缓冲盐水、GST、谷胱甘肽S-转移酶; SPR：表面等离子体共振; OP-赖氨酸：2-铵基-6-（3-氧化吡啶鎓-1-基）己酸; GLO 1：甘油二酸酶1; MG，甲基乙二醛
Advanced glycation end products (AGEs) are implicated in the development of diabetic complications via the receptor for AGEs (RAGE). We have reported that the 3-hydroxypyridinium (3HP)-containing AGEs derived from -hydroxyaldehydes physically interact with RAGE and show cytotoxicity. Lactaldehyde (LA) is formed from a reaction between threonine and myeloperoxidase, but no LA-derived AGEs have been characterized. Here, we identify the structure and physiological effects of an AGE derived from LA. We isolated a novel 3HP derivative, 2-acetamido-6-(3-hydroxy-5-methyl-pyridin-1-ium-1-yl)hexanoate, named as N-acetyl-LAPL (lactaldehyde-derived pyridinium-type lysine adduct), from a mixture of LA with N-acetyl-L-lysine. LAPL was also detected in the LA-modified protein. LAPL elicited toxicity in PC12 neuronal cells, but the effect was suppressed by the soluble form of RAGE as a decoy receptor. Moreover, surface plasmon resonance-based analysis revealed that LAPL specifically binds to recombinant RAGE. These results indicate that LA generates an AGE containing the 3HP moiety and contributes to RAGE-dependent cytotoxicity.Abbreviations: AGEs: advanced glycation end products; RAGE: receptor for advanced glycation end products; 3HP: 3-hydroxypyridinium; LA: lactaldehyde; LAPL: lactaldehyde-derived pyridinium-type lysine adduct; BSA: bovine serum albumin; GLAP: glyceraldehyde-derived pyridinium; MPO: myeloperoxidase; HFBA: heptafluorobutyric acid; TFA: trifluoroacetic acid; HPLC: high performance liquid chromatography; LC-ESI-QTOF-MS: liquid chromatography-electrospray ionization-quadrupole time-of-flight-mass spectrometry; NMR: nuclear magnetic resonance; LA-BSA: lactaldehyde-modified bovine serum albumin; PBS: phosphate buffered saline, GST, glutathione S-transferase; SPR: surface plasmon resonance; OP-lysine: 2-ammonio-6-(3-oxidopyridinium-1-yl)hexanoate; GLO1: glyoxalase 1; MG, methylglyoxal