Moroo Iku, Ujiie Maki, Walker Brandie L, Tiong Jacqueline W C, Vitalis Timothy Z, Karkan Delara, Gabathuler Reinhard, Moise Alexander R, Jefferies Wilfred A
Biotechnology Laboratory, University of British Columbia, Vancouver, Canada.
Microcirculation. 2003 Dec;10(6):457-62. doi: 10.1038/sj.mn.7800213.
This study was undertaken to assess the role of p97 (also known as melanotransferrin) in the transfer of iron into the brain, because the passage of most large molecules is limited by the presence of the blood-brain barrier, including that of the serum iron transporter transferrin.
To study the function of the soluble form of p97, we followed the uptake of radioiodinated and 55Fe loaded p97 and transferrin by the brain during a 24-hour period.
We show that the soluble form of p97 has the ability to transcytose across the murine blood-brain barrier, and its transcytosis can be inhibited in a specific manner. We also provide evidence that p97 transports iron into the brain more efficiently than transferrin.
These data support the idea that p97 is an important iron transporter across the blood-brain barrier in normal physiology and possibly in neurodegenerative diseases, such as Alzheimer disease, in which iron homeostasis in the brain becomes disrupted.
开展本研究以评估p97(也称为黑素转铁蛋白)在铁转运至脑内过程中的作用,因为包括血清铁转运蛋白转铁蛋白在内的大多数大分子的通过受到血脑屏障的限制。
为研究可溶性p97的功能,我们在24小时内追踪了脑对放射性碘化及负载55Fe的p97和转铁蛋白的摄取情况。
我们发现可溶性p97具有跨小鼠血脑屏障转胞吞的能力,且其转胞吞作用可被特异性抑制。我们还提供了证据表明p97比转铁蛋白更有效地将铁转运至脑内。
这些数据支持了这样一种观点,即p97是正常生理状态下以及可能在神经退行性疾病(如阿尔茨海默病,其中脑内铁稳态被破坏)中跨血脑屏障的重要铁转运蛋白。