S-Homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia
S-Homocysteinylation of transthyretin is detected in plasma and serum of humans with different types of hyperhomocysteinemia
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DOI：
10.1016/j.bbrc.2003.08.089
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发表时间：
2003-10-10
影响因子：
3.1
通讯作者：
Shimizu, A
中科院分区：
文献类型：
--
作者：
Sass, JO;Nakanishi, T;Shimizu, A
虽然同型半胱氨酸尿症与疾病的相关性已经知道了四十多年，但最近发现轻度高同型半胱氨酸血症是许多疾病的危险因素。然而，使（即使是轻微的）高同型半胱氨酸血症明显有害的机制尚不清楚。在高半胱氨酸衍生物高半胱氨酸硫内酯对蛋白质的N-高半胱氨酸化的报道之后，已经提出蛋白质的高半胱氨酸化可能有助于高半胱氨酸诱导生物效应。这促使我们通过电喷雾电离质谱研究不同类型的高同型半胱氨酸血症患者血浆和血清中甲状腺素运载蛋白（TTR）的同型半胱氨酸化。我们没有检测到任何N-同型半胱氨酸，但发现显着的S-同型半胱氨酸的TTR，如果总同型半胱氨酸的浓度高。我们的研究结果支持蛋白质的S-同型半胱氨酸化在高同型半胱氨酸血症的不利影响的介导中的可能作用。仔细研究个别蛋白质的翻译后修饰可能有助于更好地了解与高同型半胱氨酸血症相关的疾病。(C)2003年爱思唯尔公司All rights reserved.
While the association of homocystinuria with disease is known for more than four decades, mild hyperhomocysteinemia has been detected more recently as a risk factor for a number of diseases. However, the mechanism which apparently renders (even mild) hyperhomocystenemia harmful is not known. Following reports on N-homocysteinylation of proteins by the homocysteine derivative homocysteine thiolactone, it has been suggested that homocysteinylation of proteins may contribute to the induction of biological effects by homocysteine. This has prompted us to study by electrospray ionization mass spectrometry homocysteinylation of transthyretin (TTR) in plasma and serum of humans with different types of hyperhomocysteinemia. We did not detect any N-homocysteinylation, but found pronounced S-homocysteinylation of TTR, if the concentration of total homocysteine was high. Our findings support a possible role of S-homocysteinylation of proteins in the mediation of detrimental effects of hyperhomocysteinemia. Careful study of posttranslational modifications of individual proteins may contribute to a better understanding of diseases associated with hyperhomocysteinemia. (C) 2003 Elsevier Inc. All rights reserved.