Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation
Relationship between NF-κB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation
复制标题
DOI：
10.1006/bbrc.2000.4120
复制
发表时间：
2001-01-12
影响因子：
3.1
通讯作者：
Steer, ML
中科院分区：
文献类型：
--
作者：
Hietaranta, AJ;Saluja, AK;Steer, ML
腺泡细胞内核因子-κ B（NF-κ B）和胰蛋白酶原激活是促分泌素诱导的急性胰腺炎的早期事件。我们研究了大鼠胰腺NF-κ B与胰蛋白酶原激活的关系。CCK类似物雨蛙肽诱导早期（15分钟内）并行激活的NF-κ B和胰蛋白酶原在胰腺在体内以及在胰腺腺泡在体外。然而，NF-κ B的激活可以诱导没有胰蛋白酶原激活的脂多糖在胰腺在体内和佛波酯在胰腺腺泡在体外。在培养6小时后用雨蛙素刺激腺泡导致NF-κ B而不是胰蛋白酶原活化。蛋白酶抑制剂（AEBSF、TLCK和E64 d）抑制雨蛙素刺激的腺泡中的细胞内胰蛋白酶活性和NF-κ B活化。胰凝乳蛋白酶抑制剂（TPCK）抑制NF-κ B活化，但不抑制胰蛋白酶活性。蛋白酶体抑制剂MG-132可阻止雨蛙素诱导的NF-κ B活化，但不能阻止胰蛋白酶原活化。这些结果表明，虽然雨蛙素诱导的NF-κ B和胰蛋白酶原激活时间密切相关，它们是独立的事件在胰腺腺泡细胞。NF-κ B激活本身并不是由超最大促分泌素刺激引起的早期腺泡细胞损伤所必需的。(C)北京：科学出版社.
Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel activation of both NF-kappaB and trypsinogen in pancreas in vivo as well as in pancreatic acini in vitro. However, NF-kappaB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-kappaB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-kappaB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-kappaB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-kappaB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation. (C) 2001 Academic Press.