Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells
Heat-shock protein 27 is a major methylglyoxal-modified protein in endothelial cells
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DOI：
10.1016/j.febslet.2006.01.086
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发表时间：
2006-03-06
期刊：
影响因子：
3.5
通讯作者：
van Hinsbergh, VWM
中科院分区：
文献类型：
--
作者：
Schalkwijk, CG;van Bezu, J;van Hinsbergh, VWM
在高糖条件下培养的内皮细胞中，甲基乙二醛是形成晚期糖基化终产物的主要细胞内前体。我们发现，与5 mM D-葡萄糖相比，与30 mM D-葡萄糖孵育的内皮细胞产生约2倍高水平的甲基乙二醛，但不产生3-脱氧葡萄糖酮和乙二醛。在高血糖条件下，用特异性抗体检测到的甲基甘氨酸-精氨酸加合物精氨酸嘧啶显著升高，但N-e-（羧甲基）赖氨酸和N-e-（羧乙基）赖氨酸未检测到。乙醛酸酶I抑制剂HCCG和PPAR γ配体曲格列酮也增加了精氨酸嘧啶水平。由葡萄糖、HCCG和曲格列酮引起的精氨酸嘧啶水平的增加伴随着内皮细胞增殖的减少。一个27 kDa的蛋白被检测到作为一个主要的精嘧啶修饰的蛋白。通过凝胶内酶切和质谱分析，我们鉴定了这种主要蛋白质为热休克蛋白27（Hsp 27）。热休克蛋白27的这种精氨酸嘧啶修饰可能有助于与糖尿病相关的内皮细胞功能的变化。(c)2006年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
In endothelial cells cultured under high glucose conditions, methylglyoxal is the major intracellular precursor in the formation of advanced glycation endproducts. We found that endothelial cells incubated with 30 mM D-glucose produced approximately 2-fold higher levels of methylglyoxal but not 3-deoxyglucosone and glyoxal, as compared to 5 mM D-glucose. Under hyperglyeaemic conditions, the methylglyoxal-arginine adduct argpyrimidine as detected with a specific antibody, but not N-e-(carboxymethyl)lysine and N-e-(carboxyethyl)lysine, was significantly elevated. The glyoxylase I inhibitor HCCG and the PPAR gamma ligand troglitazone also increased argpyrimidine levels. Increased levels of argpyrimidine by glucose, HCCG and troglitazone are accompanied by a decrease in proliferation of endothelial cells. A 27 kDa protein was detected as a major argpyrimidine-modified protein. With in-gel digestion and mass spectrometric analysis, we identified this major protein as heat-shock protein 27 (Hsp27). This argpyrimidine modification of Hsp27 may contribute to changes in endothelial cell function associated to diabetes. (c) 2006 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.