JBC:用激光摧毁蛋白质淀粉斑

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发表于 2009-2-6 07:59:33 | 显示全部楼层 |阅读模式
研究者们在实验室中发现了一种能够使淀粉样纤维显影的技术,该技术有可能应用于临床治疗。该技术包括以激光消除荧光标记纤维的方法,它能抑制标记纤维的生长并将其降解。此研究发表于本周的JBC杂志,它可能为治疗淀粉斑引起的疾病,如阿兹海默症、帕金森症以及亨廷顿症提供一种非药物疗法。

Yuji Goto及其同事们致力于研究淀粉斑、蛋白质聚集体,希望能够更好的了解它们的形成机理。在一项显微镜实时检测淀粉斑形成的实验中,他们加入了一种淀粉斑特异性染色剂,名叫硫磺素T(ThT),然后用激光诱导其发出荧光。他们意外的发现,在一定条件下,激光能够停止纤维生长,甚至降解淀粉斑。

Goto及其同事们认为,激光激活ThT时将其能量转移给了周围的氧原子,使氧原子成为激活形式,引起周围蛋白质纤维发生变化。这些特定实验都集中作用于beta2-微球蛋白上,它与透析相关淀粉变(目前尚未有好的治疗方法)共同组成淀粉斑的主要成分之一。研究者们认为,类似的光诱导分解实验可能对其它类型的蛋白质淀粉斑同样起作用。(生物谷Bioon.com)

生物谷推荐原始出处:

J. Biol. Chem., Vol. 284, Issue 2, 1009-1017, January 9, 2009

Destruction of Amyloid Fibrils of a β2-Microglobulin Fragment by Laser Beam Irradiation*

Daisaku Ozawa, Hisashi Yagi, Tadato Ban, Atsushi Kameda, Toru Kawakami, Hironobu Naiki?, and Yuji Goto1

From the Institute for Protein Research, Osaka University and CREST, Japan Science and Technology Agency, Yamadaoka 3-2, Suita, Osaka 565-0871, Japan, the National Institute of Advanced Industrial Science and Technology, Midorigaoka 1-8-31, Ikeda, Osaka 563-8577, Japan, and the ?Department of Pathological Sciences, Faculty of Medical Sciences, University of Fukui and CREST, Japan Science and Technology Agency, Matsuoka, Fukui 910-1193, Japan

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.

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发表于 2009-2-6 07:59:34 | 显示全部楼层
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