MAPKs and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis
MAPKs and Hsc70 are critical to the protective effect of molecular hydrogen during the early phase of acute pancreatitis
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MAPKs 和 Hsc70 对于急性胰腺炎早期阶段氢分子的保护作用至关重要
DOI：
10.1111/febs.13629
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发表时间：
2016-02-01
期刊：
影响因子：
5.4
通讯作者：
Sun, Bei
中科院分区：
文献类型：
--
作者：
Han, Bing;Zhou, Haoxin;Sun, Bei
分子氢（H2）已被证明是一种有效的药剂，可以通过减少氧化应激来治疗多器官疾病。虽然氢对急性胰腺炎（AP）的保护作用已被证实，但其分子机制尚不清楚。在这篇文章中，我们的目的是研究胰腺细胞蛋白表达的变化与H2对AP的保护作用，并试图揭示这一过程的分子机制。蛋白质组学分析确定了73个差异表达的蛋白质，并生成了这些蛋白质的蛋白质-蛋白质相互作用网络。结果引发了我们对丝裂原活化蛋白激酶（MAPK）和热休克同源71 kDa蛋白（Hsc 70）的兴趣。随后的体外实验表明，H2处理抑制了细胞外信号调节激酶（ERK）、c-jun N-末端激酶（JNK）和p38 MAPK的磷酸化，激活了NF-κB以及肿瘤坏死因子α和白细胞介素-1 β的表达，同时阻止了磷酸化ERK、磷酸化JNK和磷酸化p38从细胞质向细胞核的移位。此外，Hsc 70的表达上调H2管理。动物实验结果与体外实验结果一致。结论：H2治疗可通过抑制MAPK通路和增加Hsc 70表达，减轻AP早期的炎症反应，降低炎症介质的表达。
Molecular hydrogen (H2) has been proven to be an effective agent that can cure multiple organ diseases by reducing oxidative stress. Although the protective effect of hydrogen on acute pancreatitis (AP) has been confirmed, its molecular mechanism is still unclear. In this article, we aimed to investigate the changes in pancreatic cell protein expression associated with the protective effect of H2 against AP and attempted to uncover the molecular mechanism underlying this process. A proteomic analysis identified 73 differentially expressed proteins and generated the protein–protein interaction networks of these proteins. The results triggered our interest in mitogen‐activated protein kinase (MAPK) and heat shock cognate 71 kDa protein (Hsc70). The subsequent in vitro experiments showed that H2 treatment inhibited the phosphorylation of extracellular signal‐regulated kinase (ERK), c‐jun N‐terminal kinase (JNK), and p38 MAPK, and activated NF‐κB and the expression of tumor necrosis factor α and interleukin‐1β, while simultaneously preventing the translocation of phospho‐ERK, phospho‐JNK, and phospho‐p38 from the cytoplasm to the nucleus. Furthermore, Hsc70 expression was upregulated by H2 administration. The animal experimental results were consistent with those of the in vitro experiments. In conclusion, H2 treatment can ameliorate the inflammatory response and reduce the expression of inflammatory mediators during the early phase of AP by inhibiting the MAPK pathways and increasing Hsc70 expression.