Yazaki Masahide, Liepnieks Juris J, Kincaid John C, Benson Merrill D
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, 975 West Walnut Street, IB 503, Indianapolis, Indiana 46202, USA.
Muscle Nerve. 2003 Oct;28(4):438-42. doi: 10.1002/mus.10452.
To elucidate the contribution of wild-type transthyretin (TTR) to amyloid polyneuropathy in TTR amyloidosis, we biochemically investigated amyloid fibrils isolated from sciatic nerve of an autopsied patient with TTR Ala25Ser variant and compared the amount of wild-type and variant TTR in the nerve to that in the heart. Amyloid subunit protein from isolated fibrils was solubilized in 6M guanidine HCl and purified by gel filtration chromatography. The relative amounts of variant and wild-type TTR in the purified protein were estimated from the recovered amounts of tryptic peptides with Ser25 or Ala25. Approximately 60% variant and 40% wild-type TTR were found in both the nerve and heart amyloid deposits. Our results indicate that wild-type TTR co-deposits in the peripheral nerves with variant TTR as amyloid fibril, and therefore that progression of amyloid deposition in the peripheral nerves from wild-type TTR may occur after liver transplantation, as has been seen in the heart.
为阐明野生型转甲状腺素蛋白（TTR）在TTR淀粉样变性中对淀粉样多神经病的作用，我们对一名患有TTR Ala25Ser变体的尸检患者坐骨神经中分离出的淀粉样纤维进行了生化研究，并将神经中野生型和变体TTR的含量与心脏中的进行了比较。从分离的纤维中提取的淀粉样亚基蛋白溶解于6M盐酸胍中，并通过凝胶过滤色谱法进行纯化。根据含Ser25或Ala25的胰蛋白酶肽的回收量，估算纯化蛋白中变体和野生型TTR的相对含量。在神经和心脏淀粉样沉积物中均发现约60%的变体TTR和40%的野生型TTR。我们的结果表明，野生型TTR与变体TTR作为淀粉样纤维共同沉积于周围神经中，因此，野生型TTR导致的周围神经淀粉样沉积进展可能在肝移植后发生，正如在心脏中所见。
