Irie Y, Keung W M
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA.
Biochem Biophys Res Commun. 2001 Mar 30;282(2):416-20. doi: 10.1006/bbrc.2001.4594.
Metallothionein-III (MT-III) protects cerebral cortical neurons in established culture from the toxic effect of amyloid beta peptides (Abetas). Protection is concentration dependent and approaches 100% at 0.1 microM. The EC(50) value estimated at 5 microM Abeta(1-40) is 2 nM. At higher concentrations (>0.1 microM), MT-III also antagonizes the trophic effect of Abeta(1-40) on cerebral cortical neurons in early cultures. Because only the fibrillar, SDS-resistant form of Abeta aggregates are thought to be neurotoxic, we analyzed and compared Abeta(1-40) aggregates formed in the presence and absence of MT-III using SDS-PAGE. Results show that aggregates formed in the absence of MT-III are predominantly SDS-resistant whereas those formed in its presence are mostly SDS-soluble. Neither MT-I nor -II exhibits any of the effects of MT-III. On the basis of these results, we propose that MT-III alleviates Abetas' neurotoxic effect by abolishing the formation of toxic aggregates of Abetas and that it may play a specific and important role in protecting the brain from the deleterious effects of Abetas.
金属硫蛋白-III（MT-III）可保护原代培养的大脑皮质神经元免受β淀粉样肽（Aβ）的毒性作用。这种保护作用呈浓度依赖性，在0.1微摩尔时接近100%。在5微摩尔Aβ（1-40）作用下，MT-III的半数有效浓度（EC50）值为2纳摩尔。在较高浓度（>0.1微摩尔）时，MT-III还会拮抗早期培养物中Aβ（1-40）对大脑皮质神经元的营养作用。由于只有纤维状、抗十二烷基硫酸钠（SDS）的Aβ聚集体被认为具有神经毒性，因此我们使用SDS聚丙烯酰胺凝胶电泳（SDS-PAGE）分析并比较了在有或没有MT-III存在的情况下形成的Aβ（1-40）聚集体。结果表明在没有MT-III的情况下形成的聚集体主要是抗SDS 的，而在有MT-III存在的情况下形成的聚集体大多是可溶于SDS的。MT-I和MT-II均未表现出MT-III的任何作用。基于这些结果，我们提出MT-III通过消除Aβ毒性聚集体的形成来减轻Aβ的神经毒性作用，并且它可能在保护大脑免受Aβ的有害影响方面发挥特定且重要的作用。
