Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.
Fibrilization in mouse senile amyloidosis is fibril conformation-dependent.
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小鼠老年淀粉样变性中的纤维化是纤维构象依赖性的。
DOI：
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发表时间：
1998
期刊：
影响因子：
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通讯作者：
M. Hosokawa
中科院分区：
文献类型：
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作者：
K. Higuchi;K. Kogishi;J. Wang;X. Chen;T. Chiba;T. Matsushita;Y. Hoshii;H. Kawano;T. Ishihara;T. Yokota;M. Hosokawa
淀粉样变性是指以淀粉样原纤维组织沉积为特征的一组疾病。单次静脉注射极少量的天然小鼠老年性淀粉样蛋白原纤维（AApoAII）可诱导具有淀粉样蛋白源性apoA-II基因（Apoa2c）的年轻小鼠发生严重的系统性淀粉样蛋白沉积。在小鼠自发性老年性淀粉样变中观察到，注射AApoAII后，淀粉样蛋白沉积迅速发生并加速进展。然而，注射变性的AApoAII、高密度脂蛋白（HDL）中的天然apoA-II和变性的apoA-II单体，它们具有相同的初级结构，但没有纤维构象，没有诱导淀粉样变性。具有抗淀粉样蛋白apoA-II基因（Apoa2b）的小鼠在注射AApoAII 3个月后也未观察到淀粉样蛋白沉积。在杂合携带两种apoA-II基因（Apoa2b/c）的小鼠中，淀粉样蛋白沉积明显减少。这些发现表明，在体外发现的核依赖性聚合也发生在体内，并且注射的淀粉样蛋白原纤维需要纤维构象才能在体内充当种子。纤维构象依赖性纤维化被认为是体内发生的各种淀粉样变性发病机制的一般模型；这可能有助于阐明淀粉样变的发病机制和开发有效的治疗方法来治疗这种疾病。
Amyloidosis refers to a group of diseases characterized by tissue deposition of amyloid fibrils. A single intravenous injection of a very small amount of the native mouse senile amyloid fibrils (AApoAII) induced severe systemic amyloid deposition in young mice having the amyloidogenic apoA-II gene (Apoa2c). After AApoAII injection, amyloid deposition occurred rapidly and advanced in an accelerated manner, as observed in spontaneous senile amyloidosis in mice. However, the injection of denatured AApoAII, native apoA-II in high-density lipoprotein (HDL), and denatured apoA-II monomer, which have the same primary structure but without a fibril conformation, did not induce amyloidosis. No amyloid deposition was observed in mice having an amyloid-resistant apoA-II gene (Apoa2b) even 3 months after AApoAII injection. Significantly less amyloid deposition was observed in mice having both types of apoA-II genes heterozygously (Apoa2b/c). These findings suggest that the nucleation-dependent polymerization found in vitro also occurs in vivo, and that the fibril conformation is required for the injected amyloid fibrils to act as seeds in vivo. Fibril conformation-dependent fibrillization is proposed as a general model of the pathogenesis of various kinds of amyloidosis occurring in vivo; it may be useful in both elucidating the pathogenesis of amyloidosis and developing effective therapeutic modalities to treat this disease.