Comparison of modification sites formed on human serum albumin at various stages of glycation.
Comparison of modification sites formed on human serum albumin at various stages of glycation.
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比较人血清白蛋白在不同糖化阶段形成的修饰位点。
DOI：
10.1016/j.cca.2010.10.018
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发表时间：
2011-01-30
期刊：
影响因子：
--
通讯作者：
Hage DS
中科院分区：
文献类型：
--
作者：
Barnaby OS;Cerny RL;Clarke W;Hage DS
糖尿病期间遇到的许多并发症可能与蛋白质的非酶糖化有关，包括人血清白蛋白（HSA）。然而，关于HSA的糖基化模式如何随着糖基化的总程度变化而变化的信息很少。本研究的目的是鉴定并半定量比较在存在不同水平糖化的情况下产生的HSA上的糖化产物。通过将生理浓度的HSA与15 mmol/l葡萄糖孵育2或5周，或与30 mmol/l葡萄糖孵育4周，在体外制备三种糖化HSA样品。然后消化这些样品，并通过基质辅助激光解吸/电离飞行时间质谱（MALDI-TOF MS）进行检查，以鉴定形成的糖化产物。结果发现，HSA的糖基化模式随着其总糖基化程度的变化而变化。许多修饰包括先前报道的主要糖化位点（例如，K199、K281和N-末端）在供试样品中一致存在。赖氨酸199和281，以及精氨酸428，含有最一致的确定和丰富的糖化产物。还发现赖氨酸93、276、286、414、439和524/525以及N-末端和丝氨酸98、197和521在不同程度的HSA糖化下被修饰。发现HSA的糖基化模式随总糖基化水平的不同而变化，并包括该蛋白上2个主要药物结合位点的修饰。这一结果表明，在糖基化的总程度和糖基化模式方面，HSA的不同修饰形式可以在糖尿病的不同阶段发现。这些结果的临床意义在于，HSA与某些药物的结合可能在糖尿病的不同阶段发生改变，因为这种蛋白质中的糖基化程度和修饰类型不同。
Many of the complications encountered during diabetes can be linked to the non-enzymatic glycation of proteins, including human serum albumin (HSA). However, there is little information regarding how the glycation pattern of HSA changes as the total extent of glycation is varied. The goal of this study was to identify and conduct a semi-quantitative comparison of the glycation products on HSA that are produced in the presence of various levels of glycation. Three glycated HSA samples were prepared in vitro by incubating physiological concentrations of HSA with 15 mmol/l glucose for 2 or 5 weeks, or with 30 mmol/l glucose for 4 weeks. These samples were then digested and examined by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to identify the glycation products that were formed. It was found that the glycation pattern of HSA changed with its overall extent of total glycation. Many modifications including previously-reported primary glycation sites (e.g., K199, K281, and the N-terminus) were consistently found in the tested samples. Lysines 199 and 281, as well as arginine 428, contained the most consistently identified and abundant glycation products. Lysines 93, 276, 286, 414, 439, and 524/525, as well as the N-terminus and arginines 98, 197, and 521, were also found to be modified at various degrees of HSA glycation. The glycation pattern of HSA was found to vary with different levels of total glycation and included modifications at the 2 major drug binding sites on this protein. This result suggests that different modified forms of HSA, both in terms of the total extent of glycation and glycation pattern, may be found at various stages of diabetes. The clinical implication of these results is that the binding of HSA to some drug may be altered at various stages of diabetes as the extent of glycation and types of modifications in this protein are varied.
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DOI：
10.1016/j.jchromb.2010.08.021
发表时间：
2010-10-15
影响因子：
3
作者：
Joseph, K. S.;Anguizola, Jeanethe;Jackson, Abby J.;Hage, David S.
通讯作者：
Hage, David S.
影响因子：
4.8
作者：
Ahmed, N;Dobler, D;Thornalley, PJ
通讯作者：
Thornalley, PJ
DOI：
10.1007/bf02872403
发表时间：
2004-01-01
期刊：
Indian journal of clinical biochemistry : IJCB
影响因子：
--
作者：
Jansirani;Anathanaryanan, P H
通讯作者：
Anathanaryanan, P H
影响因子：
3.4
作者：
LEWIS, BS;HARDING, JJ
通讯作者：
HARDING, JJ
影响因子：
1.6
作者：
Barzegar, Abolfazl;Moosavi-Movahedi, Ali A.;Norouzi, Parviz
通讯作者：
Norouzi, Parviz