Yamaguchi M, Kambayashi D, Toda J, Sano T, Toyoshima S, Hojo H
Showa College of Pharmaceutical Sciences, Higashi-tamagawagakuen, Machida, Tokyo, 194-8543, Japan.
Biochem Biophys Res Commun. 1999 Sep 16;263(1):139-42. doi: 10.1006/bbrc.1999.1289.
Acetylleucine chloromethyl ketone (ALCK), an inhibitor of acylpeptide hydrolase (ACPH), inhibited the growth of human monoblastic U937 cells in a dose- and time-dependent manner. Morphology of the ALCK-exposed cells showed typical apoptosis, judging from the nuclear condensation and segmentation. Chromosomal DNA of U937 cells treated with ALCK showed an internucleosomal ladder-like pattern on electrophoresis, being characteristic of apoptosis. Of the other leucine chloromethyl ketone analogues, butyloylleucine chloromethyl ketone (BLCK) induced a weak ladder-like formation but caploylleucine chloromethyl ketone (CLCK)barely did. On the other hand, intracellular ACPH activity of U937 cells was strongly inhibited by culturing with ALCK, moderately with BLCK, and not with CLCK. These findings indicate that the inhibition of ACPH activity leads to apoptosis and suggest that ACPH may play a vital role in eukaryotic cells.
乙酰亮氨酸氯甲基酮（ALCK），一种酰基肽水解酶（ACPH）的抑制剂，以剂量和时间依赖性方式抑制人单核细胞U937细胞的生长。从核浓缩和核分裂判断，暴露于ALCK的细胞形态显示出典型的凋亡。用ALCK处理的U937细胞的染色体DNA在电泳上呈现出核小体间梯状模式，这是凋亡的特征。在其他亮氨酸氯甲基酮类似物中，丁酰亮氨酸氯甲基酮（BLCK）诱导出较弱的梯状形成，而己酰亮氨酸氯甲基酮（CLCK）几乎没有。另一方面，通过与ALCK培养，U937细胞的细胞内ACPH活性受到强烈抑制，与BLCK培养时受到中度抑制，与CLCK培养时则不受抑制。这些发现表明ACPH活性的抑制导致凋亡，并提示ACPH可能在真核细胞中发挥重要作用。
