Destruction of Amyloid Fibrils of a β2-Microglobulin Fragment by Laser Beam Irradiation*
Destruction of Amyloid Fibrils of a β2-Microglobulin Fragment by Laser Beam Irradiation*
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DOI：
10.1074/jbc.m805118200
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发表时间：
2009-01
影响因子：
4.8
通讯作者：
Daisaku Ozawa;H. Yagi;T. Ban;A. Kameda;T. Kawakami;H. Naiki;Y. Goto
中科院分区：
文献类型：
--
作者：
Daisaku Ozawa;H. Yagi;T. Ban;A. Kameda;T. Kawakami;H. Naiki;Y. Goto
为了了解淀粉样蛋白原纤维形成的机制，我们一直在实时观察单个原纤维的生长，使用全内部荧光显微镜结合淀粉样蛋白特异性荧光染料，硫磺素T（ThT）。在中性pH下，用442 nm激光束照射以激发ThT抑制β2-微球蛋白（β2-m）的纤维生长，β2-m是透析相关淀粉样变性患者中沉积的淀粉样纤维的主要成分。用β2-m的22个残基的K3片段进行的检测表明，抑制纤维生长以及破坏预先形成的纤维与ThT的激发相耦合。一些证据表明，激发的ThT将能量转移到基态分子氧，产生活性氧，从而引起各种类型的化学修饰。这些结果意味着一种新的策略，防止淀粉样纤维的沉积和破坏预先形成的淀粉样沉积物。
To understand the mechanism by which amyloid fibrils form, we have been making real-time observations of the growth of individual fibrils, using total internal fluorescence microscopy combined with an amyloid-specific fluorescence dye, thioflavin T (ThT). At neutral pH, irradiation at 442 nm with a laser beam to excite ThT inhibited the fibril growth of β2-microglobulin (β2-m), a major component of amyloid fibrils deposited in patients with dialysis-related amyloidosis. Examination with a 22-residue K3 fragment of β2-m showed that the inhibition of fibril growth and moreover the destruction of preformed fibrils were coupled with the excitation of ThT. Several pieces of evidence suggest that the excited ThT transfers energy to ground state molecular oxygen, producing active oxygen, which causes various types of chemical modifications. The results imply a novel strategy for preventing the deposition of amyloid fibrils and for destroying preformed amyloid deposits.