Trypsinogen activation in rat pancreatic acinar cells hyperstimulated by caerulein

被引:19
作者
Halangk, W
Stürzebecher, J
Matthias, R
Schulz, HU
Lippert, H
机构
[1] Univ Magdeburg, Dept Expt Surg, Ctr Surg, D-39120 Magdeburg, Germany
[2] Univ Jena, Ctr Vasc Biol & Med Erfurt, D-99089 Erfurt, Germany
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE | 1997年 / 1362卷 / 2-3期
关键词
rhodamine 110-based substrate; cathepsin B inhibitor; benzamidine; trypsin(ogen); pancreatic acinar cell;
D O I
10.1016/S0925-4439(97)00082-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Inappropriate trypsinogen activation is discussed as an early intracellular event in the secretagogue-induced model of acute pancreatitis. However, the mechanisms by which trypsinogen is activated are not well characterized. In the present work, trypsinogen activation was studied in intact acinar cells using bis-(CBZ-arginyl)-Rhodamine 110 [(CBZ-Arg)(2)-Rho 110] as a cell-permeant substrate for trypsin and also independently via the formation of trypsinogen activation peptide (TAP). Preincubation with 10nM caerulein increased the Rho 110-substrate cleavage more than threefold. This proteolytic activity was fully sensitive to a benzamidine (BA)-type serine protease inhibitor. The appearance of enzymatic activity was paralleled by the formation of TAP. The lack of effect of the high-molecular soybean trypsin inhibitor indicates an intracellular substrate cleavage. The cathepsin B inhibitor CA-074 prevented neither the caerulein-induced formation of TAP nor the (CBZ-Arg)(2) Rho 110-cleaving activity. BA inhibited the Rho 110-substrate cleavage and significantly reduced the TAP formation. These results show that trypsinogen activation in caerulein-hyperstimulated acinar cells may occur independently of the activity of cathepsin B. On the contrary, the effect of BA suggests the role of a serine protease in trypsinogen activation. (C) 1997 Elsevier Science B.V.
引用
收藏
页码:243 / 251
页数:9
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