Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase
Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase
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DOI：
10.1016/j.peptides.2011.08.027
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发表时间：
2011-10-01
期刊：
影响因子：
3
通讯作者：
Takayanagi, Ryoichi
中科院分区：
文献类型：
--
作者：
Fujimori, Nao;Oono, Takamasa;Takayanagi, Ryoichi
血管活性肠肽(VIP)通过抑制炎症细胞产生细胞因子来减轻实验性急性胰腺炎(AP)。已有研究表明，活性氧(ROS)和细胞因子在AP的早期病理生理过程中起着关键作用。本研究旨在阐明血管活性肠肽对胰腺，尤其是胰腺腺泡细胞氧化状态的影响。用CM-H(2)DCFDA评估，过氧化氢(H(2)O(2))诱导的细胞内ROS增加，呈时间和剂量依赖性。用四甲基偶氮唑盐比色法测定ROS对细胞的损伤作用，结果表明，随着浓度的增加，细胞存活率下降。VIP显著抑制腺泡细胞产生ROS，并以剂量依赖的方式增加细胞存活率。除SOD2外，VIP对过氧化氢酶、谷胱甘肽还原酶、超氧化物歧化酶和谷胱甘肽过氧化物酶等抗氧化剂的表达无明显影响。此外，NADPH氧化酶的主要成分NOX1和NOX2在胰腺腺泡内均有表达，H(2)O(2)处理后表达显著增加。H(2)O(2)对NADPH氧化酶活性有激活作用。VIP降低NADPH氧化酶活性，该作用可被PICA抑制剂H89消除。这些结果表明，VIP通过诱导cAMP/PKA途径影响ROS的产生机制，包括NADPH氧化酶。综上所述，VIP通过抑制NADPH氧化酶减少腺泡细胞的氧化应激。这些结果结合我们以前的研究结果表明，VIP在胰腺损伤中发挥保护作用，不仅通过抑制细胞因子的产生，而且通过减轻氧化应激引起的损伤。(C)2011 Elsevier Inc.保留所有权利。
Vasoactive intestinal peptide (VIP) attenuates experimental acute pancreatitis (AP) by inhibition of cytokine production from inflammatory cells. It has been suggested that reactive oxygen species (ROS) as well as cytokines play pivotal roles in the early pathophysiology of AP. This study aimed to clarify the effect of VIP on the oxidative condition in pancreas, especially pancreatic acinar cells (acini). Hydrogen peroxide (H(2)O(2))-induced intracellular ROS, assessed with CM-H(2)DCFDA, increased time- and dose-dependently in acini isolated from rats. Cell viability due to ROS-induced cellular damage, evaluated by MTS assay, was decreased with >= 100 mu mol/L H(2)O(2). VIP significantly inhibited ROS production from acini and increased cell viability in a dose-dependent manner. Expression of antioxidants including catalase, glutathione reductase, superoxide dismutase (SOD) 1 and glutathione peroxidase was not altered by VIP except for SOD2. Furthermore, Nox1 and Nox2, major components of NADPH oxidase, were expressed in pancreatic acini, and significantly increased after H(2)O(2) treatment. Also, NADPH oxidase activity was provoked by H(2)O(2). VIP decreased NADPH oxidase activity, which was abolished by PICA inhibitor H89. These results suggested that VIP affected the mechanism of ROS production including NADPH oxidase through induction of a cAMP/PKA pathway. In conclusion, VIP reduces oxidative stress in acini through the inhibition of NADPH oxidase. These results combined with findings of our previous study suggest that VIP exerts its protective effect in pancreatic damage, not only through an inhibition of cytokine production, but also through a reduction of the injury caused by oxidative stress. (C) 2011 Elsevier Inc. All rights reserved.