Richardson J S, Zhou Y, Kumar U
Department of Pharmacology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Ann N Y Acad Sci. 1996 Jan 17;777:362-7. doi: 10.1111/j.1749-6632.1996.tb34446.x.
The fragment of the beta-amyloid protein that contains the peptide sequence 25 to 35 of the parent compound, increases cytosolic calcium and is directly cytotoxic to neurons in tissue culture. The cytotoxic action of beta-amyloid has been considered to be the primary determinant of the neurodegeneration observed in Alzheimer's disease. The cytotoxic effects of beta-amyloid 25-35 or beta-amyloid 1-40 added to primary cultures of rat hippocampal or cortical neurons can be reduced or prevented by anti-oxidant lazaroid drugs such as U-74500A, U-78517F, or U-83836E. beta-amyloid 25-35 evokes an immediate increase in cytosolic calcium when added to suspensions of PC 12 cells, and is cytotoxic to PC 12 cells in tissue culture. Both the calcium-elevating and the cytotoxic actions of beta-amyloid 25-35 on PC 12 cells are reduced or prevented by lazaroid anti-oxidant drugs. Since the lazaroids have been shown to scavenge free radical species, the present results indicate that the actions of beta-amyloid 25-35 on calcium regulation and on cell survival are mediated by free radicals.
β-淀粉样蛋白片段包含母体化合物的肽序列25至35，可增加胞质钙并对组织培养中的神经元具有直接细胞毒性。β-淀粉样蛋白的细胞毒性作用被认为是阿尔茨海默病中观察到的神经退行性变的主要决定因素。添加到大鼠海马或皮质神经元原代培养物中的β-淀粉样蛋白25-35或β-淀粉样蛋白1-40的细胞毒性作用可被抗氧化剂拉扎罗类药物如U-74500A、U-78517F或U-83836E降低或阻止。β-淀粉样蛋白25-35添加到PC 12细胞悬液中会立即引起胞质钙升高，并且对组织培养中对PC 12细胞具有细胞毒性。拉扎罗类抗氧化剂药物可降低或阻止β-淀粉样蛋白25-35对PC 12细胞的钙升高和细胞毒性作用。由于已证明拉扎罗类药物可清除自由基，目前的结果表明β-淀粉样蛋白25-35对钙调节和细胞存活的作用是由自由基介导的。
