Brodt-Eppley J, Hui D Y
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529.
Biochem J. 1995 Mar 1;306 ( Pt 2)(Pt 2):605-8. doi: 10.1042/bj3060605.
The bile salt-stimulated cholesterol esterase is a digestive enzyme synthesized by the acinar cells of the pancreas. Previous results have shown that cholesterol esterase biosynthesis and secretion in the AR42J pancreatoma cells could be increased 3-5-fold by intestinal hormones such as cholecystokinin (CCK). The purpose of the current study is to explore the signalling mechanism by which CCK stimulation of AR42J cells results in increased biosynthesis and secretion of the cholesterol esterase. The results showed that the CCK-induced cholesterol esterase secretion could be mimicked by addition of the Ca2+ ionophore A23187 or by transient incubation of AR42J cells with the protein kinase C activator phorbol 12-myristate 13-acetate (PMA). Cholesterol esterase stimulation by CCK, A23187 and PMA could be abolished by the calcium chelator BAPTA or by specific protein kinase C inhibitors such as chelerythrine. Additionally, prolonged incubation of AR42J cells with PMA to reduce the protein kinase C level, also reduced CCK-stimulated cholesterol esterase secretion to a level similar to that observed in control cells. Taken together, these data suggested that CCK activation of cholesterol esterase secretion may be mediated by a Ca(2+)-dependent protein kinase C pathway, requiring increases in calcium mobilization and activation of protein kinase C.
胆盐刺激的胆固醇酯酶是一种由胰腺腺泡细胞合成的消化酶。先前的研究结果表明，胆囊收缩素（CCK）等肠道激素可使AR42J胰腺癌细胞中的胆固醇酯酶生物合成和分泌增加3至5倍。本研究的目的是探讨CCK刺激AR42J细胞导致胆固醇酯酶生物合成和分泌增加的信号传导机制。结果显示，添加Ca2+离子载体A23187或用蛋白激酶C激活剂佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）短暂孵育AR42J细胞，可模拟CCK诱导的胆固醇酯酶分泌。CCK、A23187和PMA对胆固醇酯酶的刺激作用可被钙螯合剂BAPTA或诸如白屈菜红碱等特异性蛋白激酶C抑制剂消除。此外，用PMA长时间孵育AR42J细胞以降低蛋白激酶C水平，也会使CCK刺激的胆固醇酯酶分泌降低至与对照细胞中观察到的水平相似。综上所述，这些数据表明CCK激活胆固醇酯酶分泌可能是由Ca(2+)依赖性蛋白激酶C途径介导的，需要钙动员增加和蛋白激酶C激活。
