Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus.

Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus.
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DOI:
10.1073/pnas.78.8.5190
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发表时间:
1981-08
影响因子:
11.1
通讯作者:
H. Vlassara;M. Brownlee;A. Cerami
H. Vlassara;M. Brownlee;A. Cerami
中科院分区:
综合性期刊1区
文献类型:
--
作者:
H. Vlassara;M. Brownlee;A. Cerami

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一种新的亲和色谱系统,选择性地保留糖基化的氨基酸已被用来确定糖尿病和对照大鼠和狗的外周神经中存在的非酶糖基化的量。糖尿病大鼠糖基化氨基酸平均值是正常大鼠的2.8倍(P <0.001)。在糖尿病犬中,平均值是正常值的2.15倍(P <0.05)。先前通过亲和色谱分离的还原的糖基化氨基酸的氨基酸分析表明,糖基化赖氨酸及其水解重排产物是存在的主要硼氢化物可还原加合物。此外,观察到另一种糖基化产物以较大比例存在。该放射性产物未使用任何可用的糖基化氨基酸标准品进行色谱分析。糖尿病导致周围神经糖基化增加近3倍的发现与之前的许多研究一致,其中在糖尿病患者和正常人的血红蛋白、血清白蛋白和尿氨基酸和肽中测量糖基化。本文报告的结果提供了证据,表明非酶糖基化增加发生在组织中,其中生理学、形态学和临床变性特征性地发展为糖尿病的结果。
A new affinity chromatography system that selectively retains glycosylated amino acids has been utilized to determine the amount of nonenzymatic glycosylation present in peripheral nerve from diabetic and control rats and dogs. The mean value for glycosylated amino acids in diabetic rats was 2.8 times greater than the mean value in normal rats (P less than 0.001). In diabetic dogs, mean values were 2.15 times greater than normal values (P less than 0.05). Amino acid analysis of reduced, glycosylated amino acids previously isolated by affinity chromatography showed that glycosylated lysine and its hydrolysis rearrangement products were the major borohydride-reducible adduct present. In addition, another glycosylated product was noted to be present in major proportions. This radioactive product did not chromatograph with any of the available glycosylated amino acid standards. The finding that diabetes results in a nearly 3-fold increase of peripheral nerve glycosylation is consistent with a number of previous investigations in which glycosylation was measured in hemoglobin, serum albumin, and urinary amino acids and peptides from diabetics and normals. The results reported here provide evidence that increased nonenzymatic glycosylation is occurring in a tissue where physiological, morphological, and clinical degeneration characteristically develop as a result of diabetes mellitus.