The function of oxidative stress-inducible proteins in pancreas-implication in pathogenesis of pancreatitis and diabetes-

氧化应激诱导蛋白被认为是细胞中抗氧化系统的一种。在这项研究中，我们研究了氧化应激诱导蛋白，血红素加氧酶（HO）和MSP23作为我们发现的氧化应激诱导蛋白。为了研究HO在急性胰腺炎中的表达，我们通过腹腔注射一种十肽胆囊收缩素类似物——小蛋白来诱导大鼠胰腺炎。用小粒蛋白处理大鼠后1h胰腺中未检测到诱导型HO-1表达，但在小粒蛋白处理大鼠中观察到间质水肿。在给药12-24 h后，HO-1在胰腺组织中选择性表达，而组成型HO-2和MSP23的表达保持不变。在小鼠胰岛（BETATC3）和大鼠腺泡（AR42J）胰腺细胞系中，氧化应激如过氧化氢、紫紫甲基、氯化镉和马来酸二乙酯以剂量和时间依赖性方式增强HO-1表达，而不改变HO-2和MSP23.3的表达。BETATC3对氧化应激的敏感性与AR42J细胞不同。因此，我们研究了这些细胞内的谷胱甘肽水平。AR42J细胞的谷胱甘肽水平明显高于BETATC3细胞。结果表明，AR42J细胞中较高的谷胱甘肽水平反映了较高的胱氨酸转运活性，胱氨酸是谷胱甘肽合成的限速前体氨基酸。这些结果提示氧化应激诱导蛋白在急性胰腺炎中起重要作用。这些蛋白与糖尿病的关系值得进一步探讨。

The oxidative stress-inducible proteins are thought to function as one of the anti-oxidant systems in the cells. In this study, we have investigatad oxidative stress-inducible proteins, heme oxygenase (HO) and MSP23 as an oxidative stress-inducible protein found by us.1. To investigate expression of HO in acute pancreatitis, pancreatitis was induced in rats by adminstering caerulein, a decapeptide cholecystokinin analogue, intraperitoneally. Inducible form HO-1 expression was not detected in the pancreas 1h after treatment of rats with caerulein, although interstitial oedema was observed in caerulein-treated rats. HO-1 was expressed selectively in pancreatic tissue 12-24 h after treatment of rats with caerulein, whereas expression of the constitutive form HO-2 and MSP23 remained unchanged.2. In murine islet (BETATC3) and rat acinar (AR42J) pancreatic cell lines, oxidative stress such as hydrogen peroxide, methyl viologen, cadmium chloride, and diethylmaleate enhanced HO-1 expression in a dose-and time-dependent manner without altering expression of HO-2 and MSP23.3. The sensitivity of BETATC3 to oxidative stress was different from that of AR42J cells. Therefore, we investigated the intracellular glutathione levels in these cells. The glutathione level in AR42J cells was significantly higher than that in BETATC3 cells. It was demonstrated that the higher level of glutathione in AR42J cells reflected the higher transport activity of cystine, which is a rate-limiting precursor amino acid for glutathione synthesis.From these results, it was suggested that oxidative stress-inducible proteins play an important role in acute pancreatitis. The relationship between these proteins and diabetes deserves further exploration.