Figueiredo-Pereira M E, Berg K A, Wilk S
Department of Pharmacology, Mount Sinai School of Medicine, CUNY, New York 10029.
J Neurochem. 1994 Oct;63(4):1578-81. doi: 10.1046/j.1471-4159.1994.63041578.x.
Exposure of HT4 cells (a mouse neuronal cell line) to a new potent permeable peptidyl aldehyde inhibitor of the chymotrypsin-like activity of the multicatalytic proteinase complex (MPC) causes accumulation of ubiquitinylated proteins. In contrast, inhibition of calpain or treatment with a lysosomotropic agent failed to produce detectable ubiquitin-protein conjugates. The appearance of such conjugates is not a nonspecific phenomenon because incubation with the peptidyl alcohol analogue of the inhibitor does not produce accumulation of ubiquitinylated proteins. The MPC inhibitor may therefore be a useful tool for identification and study of physiological pathways involving MPC. Furthermore, the inhibitor may help develop a model for the study of neurodegeneration where accumulation of ubiquitin-protein conjugates is commonly detected in abnormal brain inclusions.
将HT4细胞（一种小鼠神经元细胞系）暴露于一种新型的、强效的、可渗透的肽基醛类多催化蛋白酶复合物（MPC）糜蛋白酶样活性抑制剂中，会导致泛素化蛋白的积累。相比之下，抑制钙蛋白酶或用溶酶体促渗剂处理均未能产生可检测到的泛素 - 蛋白缀合物。此类缀合物的出现并非非特异性现象，因为用该抑制剂的肽醇类似物孵育不会导致泛素化蛋白的积累。因此，MPC抑制剂可能是用于鉴定和研究涉及MPC的生理途径的有用工具。此外，该抑制剂可能有助于建立一个研究神经退行性变的模型，在异常脑内含物中通常可检测到泛素 - 蛋白缀合物的积累。
