Mandal Pravat K, Williams John P, Mandal Ratna
Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15213, USA.
Biochemistry. 2007 Jan 23;46(3):762-71. doi: 10.1021/bi062184l.
Abeta peptide is the major component of senile plaques (SP), which accumulate in the brain of a patient with Alzheimer's disease (AD). A recent report indicated that isoflurane enhanced Abeta oligomerization (micro-aggregation) and subsequent cytotoxicity of the Abeta peptide. A separate study showed that a clinically relevant concentration of isoflurane induces apoptosis and increases Abeta production in a human neuroglioma cell line. In vitro studies have indicated that halothane interacts specifically with Abeta peptide to induce oligomerization and that Abeta42 oligomerizes faster than Abeta40. The specific interactions of isoflurane, propofol, and thiopental with uniformly 15N labeled Abeta40 and Abeta42 peptide were investigated using multidimensional nuclear magnetic resonance (NMR) experiments. We found that isoflurane and propofol (at higher concentration) interact with Abeta40 peptides and induce Abeta oligomerization. Thiopental does not interact with specific residues (G29, A30, and I31) of Abeta40; hence, the peptide remains in the monomeric form. On the basis of our NMR study, thiopental does not oligomerize Abeta40 even at higher concentrations.
β淀粉样肽是老年斑（SP）的主要成分，老年斑会在阿尔茨海默病（AD）患者的大脑中积累。最近的一份报告表明，异氟烷会增强β淀粉样肽的寡聚化（微聚集）以及随后的细胞毒性。另一项研究表明，临床相关浓度的异氟烷会诱导人神经胶质瘤细胞系发生凋亡并增加β淀粉样肽的产生。体外研究表明，氟烷与β淀粉样肽特异性相互作用以诱导寡聚化，并且β淀粉样蛋白42比β淀粉样蛋白40更快地发生寡聚化。使用多维核磁共振（NMR）实验研究了异氟烷、丙泊酚和硫喷妥钠与均匀标记15N的β淀粉样蛋白40和β淀粉样蛋白42肽的特异性相互作用。我们发现异氟烷和丙泊酚（在较高浓度下）与β淀粉样蛋白40肽相互作用并诱导β淀粉样肽寡聚化。硫喷妥钠不与β淀粉样蛋白40的特定残基（G29、A30和I31）相互作用；因此，该肽保持单体形式。基于我们的核磁共振研究，即使在较高浓度下，硫喷妥钠也不会使β淀粉样蛋白40发生寡聚化。
