The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis.
The pancreatitis-associated protein is induced by free radicals in AR4-2J cells and confers cell resistance to apoptosis.
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DOI：
10.1016/s0016-5085(98)70595-5
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发表时间：
1998-04
期刊：
影响因子：
29.4
通讯作者：
E. Ortiz;N. Dusetti;S. Vasseur;David Malka;Hans Bödeker;Jean-Charles Dagorn;Juan L. Iovanna
中科院分区：
文献类型：
--
作者：
E. Ortiz;N. Dusetti;S. Vasseur;David Malka;Hans Bödeker;Jean-Charles Dagorn;Juan L. Iovanna
背景与目的自由基参与了急性胰腺炎的发病过程，在此过程中，胰腺炎相关蛋白-I(PAP-I)过度表达。方法将AR4-2J细胞暴露于过氧化氢或甲萘二酮中，用Northern印迹法检测PAP-I信使核糖核酸的表达。结果氧化应激诱导AR4-2J细胞表达PAP-I的能力最强。12小时后可检测到诱导作用，18小时达到高峰，然后下降。用吡咯烷二硫代氨基甲酸酯处理细胞后，PAP-ImRNA的诱导完全消失，提示NFκB参与了信号转导途径。这些发现在使用含有与氯霉素乙酰转移酶报告基因相连的PAP-I启动子的质粒的瞬时转染试验中得到证实。然后考虑了PAP-I的诱导与氧化应激过程中细胞损伤保护的关系。转染PAP-I互补DNA后的AR4-2J细胞表达PAP-I，对低剂量的过氧化氢诱导的细胞凋亡有明显的抵抗作用，但对高剂量的过氧化氢诱导的细胞坏死无明显影响。结论在氧化应激过程中，PAP-I可能是胰腺细胞保护凋亡的机制之一。胃肠病学1998；114：808-816
Background & AimsFree radicals are involved in the pathogenesis of acute pancreatitis, during which pancreatitis-associated protein (PAP)-I is overexpressed. We explored whether PAP-I expression could be induced by oxidative stress and whether it could affect apoptosis.MethodsAR4-2J cells were exposed to H2O2or menadione, and PAP-I messenger RNA (mRNA) expression was analyzed by Northern blotting.ResultsMaximal expression was observed with 0.1 mmol/L H2O2or with 0.05 mmol/L menadione. Induction was detectable after 12 hours, reached a climax at 18 hours, and then decreased. Pretreatment of the cells with pyrrolidine dithiocarbamate completely abolished PAP-I mRNA induction, suggesting involvement of NFκB in the signaling pathway. These findings were confirmed in transient transfection assays using a plasmid containing the PAP-I promoter linked to the chloramphenicol acetyltransferase reporter gene. Then the relationship between PAP-I induction and protection against cell damage during oxidative stress was considered. Constitutive PAP-I expression in AR4-2J cells after transfection with PAP-I complementary DNA conferred significant resistance to apoptosis induced by low doses of H2O2but not to necrosis induced by high doses of H2O2.ConclusionsThese results suggest that during oxidative stress, PAP-I might be part of a mechanism of pancreatic cell protection against apoptosis. GASTROENTEROLOGY 1998;114:808-816