Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils and protein A amyloid fibrils
Cross-seeding and cross-competition in mouse apolipoprotein A-II amyloid fibrils and protein A amyloid fibrils
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DOI：
10.2353/ajpath.2007.060576
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发表时间：
2007-07-01
影响因子：
6
通讯作者：
Higuchi, Keiichi
中科院分区：
文献类型：
--
作者：
Yan, Jingmin;Fu, Xiaoying;Higuchi, Keiichi
据报道，小鼠老年性[载脂蛋白A- ii淀粉样蛋白（AApoAII）]和反应性[蛋白A淀粉样蛋白（AA）]淀粉样变是通过与朊病毒相关疾病相似的种子机制传播的疾病，尽管新淀粉样蛋白形成和AApoAII或AA淀粉样变的进展尚不清楚。我们检测了在R1中联合注射AApoAII和AA原纤维和多种炎症刺激的影响。P1-Apoa2(c)携带淀粉样变性Apoa2(c)等位基因的小鼠。该系统均可诱导AApoAII和AA淀粉样变，但两种淀粉样原纤维优先促进同一种淀粉样原纤维的形成，而抑制另一种淀粉样原纤维的形成。此外，我们证明了AA或AApoAII淀粉样变性可以通过预沉积的AApoAII或AA原纤维进行交叉播种，并且当原纤维形成减少或停止时，预沉积的淀粉样原纤维被降解。此外，这两种淀粉样蛋白原纤维在脾和肝中形成新原纤维的过程中有很大比例的共定位。因此，我们提出AApoAII和AA在淀粉样蛋白形成方面既可以交叉种子也可以交叉竞争，这取决于淀粉样蛋白形成的阶段。这些结果有助于阐明淀粉样蛋白疾病的发病机制和进展。
Murine senile [apolipoprotein A-II amyloid (AApoAII)] and reactive [protein A amyloid (AA)] amyloidosis are reported to be transmissible diseases via a seeding mechanism similar to that observed in the prion-associated disorders, although de novo amyloidogenesis and the progression of AApoAII or AA amyloidosis remain unclear. We examined the effect of coinjection of AApoAII and AA fibrils and multiple inflammatory stimuli in R1.P1-Apoa2(c) mice with the amyloidogenic Apoa2(c) allele. Both AApoAII and AA amyloidosis could be induced in this system, but the two types of amyloid fibrils preferentially promote the formation of the same type of fibrils while inhibiting the formation of the other. Furthermore, we demonstrate that AA or AApoAII amyloidosis could he cross-seeded by predeposited AApoAII or AA fibrils and that the predeposited amyloid fibrils were degraded when the fibril formation was reduced or stopped. In addition, a large proportion of the two amyloid fibrils colocalized during the formation of new fibrils in the spleen and liver. Thus, we propose that AApoAII and AA can both cross-seed and cross-compete with regard to amyloid formation, depending on the stage of amyloidogenesis. These results win aid in the clarification of the mechanisms of pathogenesis and progression of amyloid disorders.