Essalmani R, Macq A F, Mercken L, Octave J N
Université Catholique de Louvain, Laboratoire de Neurochimie, UCL 1080, Brussels, Belgium.
Biochem Biophys Res Commun. 1996 Jan 5;218(1):89-96. doi: 10.1006/bbrc.1996.0017.
Production of soluble amyloid peptide precursor (APP) and amyloid peptide (A beta) was measured in CHO cells transfected by the wild-type APP 695 cDNA sequence or by the same sequence carrying missense mutations associated with familial Alzheimer's disease in Sweden. Deletion of the C-terminal domain of the protein corresponding to residues 654 to 695 of APP 695 not only inhibited very significantly the internalization of APP at 37 degrees C, but also led to the secretion of an uncleaved APP in the culture medium of CHO cells. This deletion did not affect A beta production from the Swedish APP but was able to inhibit the production of the wild-type APP. These results demonstrate that, in CHO cells, the internalization of the wild-type APP is needed for A beta production, while the production of the amyloid peptide from Swedish APP is independent of the internalization process.
在转染了野生型APP 695 cDNA序列或携带与瑞典家族性阿尔茨海默病相关错义突变的相同序列的CHO细胞中，检测了可溶性淀粉样肽前体（APP）和淀粉样肽（Aβ）的产生。缺失与APP 695的654至695位残基相对应的蛋白质C末端结构域，不仅在37℃时非常显著地抑制了APP的内化，而且导致未切割的APP在CHO细胞培养基中分泌。这种缺失不影响瑞典APP产生Aβ，但能够抑制野生型APP的产生。这些结果表明，在CHO细胞中，野生型APP的内化是产生Aβ所必需的，而瑞典APP产生淀粉样肽则与内化过程无关。
