Kishikawa M
Department of Clinical Pathology, Osaka Medical College, Takatsuki.
Rinsho Byori. 2000 May;48(5):430-6.
We analyzed wild-type and variant transthyretins (TTRs) by mass spectrometry and reported that all TTR preparations demonstrated free TTR, TTR conjugated with thiol compounds and several minor components. We previously described a component with a molecular mass 80 Da larger than free TTR, which was proven to be TTR conjugated with bisulfite. The amyloid fibril formation of purified TTR was monitored by the turbidity at 330 nm, and by a Congo red binding assay as a function of pH. The S-sulfonated TTR showed clear elevation of the turbidity and Congo red binding under acidic conditions. In contrast, TTR reduced by dithiothreitol, which was free of the S-sulfonated component, did not show evidence of amyloid fibril formation. We analyzed rabbit serum TTR obtained from a rabbit fed a diet containing sulfite and from a rabbit on a sulfite-free diet. Compared to that in the rabbit fed a sulfite-containing diet, sulfonated TTR was decreased on the 7th day of a sulfite-free diet. These results suggested that the S-sulfonated wild-type TTR is highly amyloidogenic, and that prolonged ingestion of antimicrobial and antioxidant agents containing sulfite/bisulfite, may cause senile systemic amyloidosis.
我们通过质谱分析了野生型和变异型转甲状腺素蛋白（TTR），并报告称所有TTR制剂均显示出游离TTR、与硫醇化合物结合的TTR以及几种次要成分。我们之前描述过一种分子量比游离TTR大80 Da的成分，后来证明它是与亚硫酸氢盐结合的TTR。通过监测330 nm处的吸光度以及刚果红结合试验作为pH的函数，来观察纯化TTR的淀粉样纤维形成情况。在酸性条件下，S-磺化TTR的吸光度和刚果红结合明显升高。相比之下，用二硫苏糖醇还原且不含S-磺化成分的TTR未显示出淀粉样纤维形成的迹象。我们分析了从喂食含亚硫酸盐饮食的兔子和无亚硫酸盐饮食的兔子身上获取的兔血清TTR。与喂食含亚硫酸盐饮食的兔子相比，在无亚硫酸盐饮食的第7天，磺化TTR减少。这些结果表明，S-磺化野生型TTR具有高度的淀粉样变性，长期摄入含亚硫酸盐/亚硫酸氢盐的抗菌和抗氧化剂可能会导致老年系统性淀粉样变性。
