Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats
Water immersion stress induces heat shock protein 60 expression and protects against pancreatitis in rats
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DOI：
10.1053/gast.2000.8551
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发表时间：
2000-07-01
期刊：
影响因子：
29.4
通讯作者：
Saluja, AK
中科院分区：
文献类型：
--
作者：
Lee, HS;Bhagat, L;Saluja, AK
背景与目的：热休克蛋白（Heat shock proteins，Hsps）是由细胞应激诱导产生的一种细胞保护蛋白。最近的研究表明，热休克蛋白60的表达，诱导暴露于水浸应激，保护对胰腺炎引起的管理超大剂量雨蛙肽在大鼠。然而，负责这种保护的机制尚不清楚。方法：大鼠浸水3-12 h。胰腺炎由雨蛙肽给药诱导。结果如下：结果证实，通过水浸应激诱导Hsp 60表达可显著改善蛙皮素诱导的胰腺炎的严重程度，这可通过显著降低高淀粉酶血症、胰腺水肿和腺泡细胞坏死程度来判断。水浸也可防止组织蛋白酶B从富含溶酶体的组分向较重的富含酶原颗粒的组分的亚细胞再分布，这在胰腺炎模型中是已知的。腺泡内细胞激活胰蛋白酶原，发生后不久，暴露于一个超大刺激剂量的雨蛙肽在体内和体外的预先水浸应力和Hsp 60的表达被阻止。水浸应激后对胰腺炎的保护不是由胆囊收缩素受体的改变引起的，因为水浸不会改变对雨蛙肽刺激的典型双相淀粉酶分泌反应。结论：水浸应激诱导热休克蛋白60的表达，改善蛙皮素诱导的胰腺炎，并防止腺泡细胞内的胰蛋白酶原激活。我们认为，热休克蛋白60通过阻止腺泡细胞内的胰蛋白酶原激活来防止蛙皮素诱导的胰腺炎。
Background & Aims: Heat shock proteins (Hsps), induced by cell stress, are known to protect against cellular injury. Recent studies have indicated that Hsp60 expression, induced by exposure to water immersion stress, protects against pancreatitis induced by administration of supramaximal doses of cerulein in rats. However, the mechanisms responsible for this protection are not known. Methods: Rats were water-immersed for 3-12 hours. Pancreatitis was induced by cerulein administration. Results: The results confirm that prior induction of Hsp60 expression by water-immersion stress significantly ameliorates the severity of cerulein-induced pancreatitis as judged by the markedly reduced degree of hyperamylasemia, pancreatic edema, and acinar cell necrosis. Water immersion also prevents the subcellular redistribution of cathepsin B from a lysosome-enriched fraction to a heavier, zymogen granule-enriched fraction that is known to occur in this model of pancreatitis. Intra-acinar cell activation of trypsinogen that occurs shortly after exposure to a supramaximally stimulating dose of cerulein both in vivo and in vitro is prevented by prior water-immersion stress and Hsp60 expression. The protection against pancreatitis that follows water-immersion stress is not caused by alterations of cholecystokinin receptors, because water immersion does not alter the typical biphasic amylase secretory response to stimulation with cerulein. Conclusions: Water-immersion stress induces Hsp60 expression, ameliorates cerulein-induced pancreatitis, and prevents intra-acinar cell activation of trypsinogen. We suggest that Hsp60 protects against cerulein-induced pancreatitis by preventing trypsinogen activation within acinar cells.