Molecular hydrogen suppresses FcεRI-mediated signal transduction and prevents degranulation of mast cells
Molecular hydrogen suppresses FcεRI-mediated signal transduction and prevents degranulation of mast cells
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DOI：
10.1016/j.bbrc.2009.09.047
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发表时间：
2009-11-27
影响因子：
3.1
通讯作者：
Ito, Masafumi
中科院分区：
文献类型：
--
作者：
Itoh, Tomohiro;Fujita, Yasunori;Ito, Masafumi
分子氢改善动物模型中氧化应激相关疾病。我们发现，口服富含氢的水可以消除小鼠的速发型过敏反应。使用大鼠RBL-2 H3肥大细胞，我们证明了氢减弱了Fc γ RI相关林恩的磷酸化及其下游信号转导，随后抑制NADPH氧化酶活性并减少过氧化氢的产生。我们还发现，抑制NADPH氧化酶减弱肥大细胞中林恩的磷酸化，表明存在一个前馈回路，加强过敏反应。因此，氢抑制环中所有测试的信号传导分子。氢的影响已被完全归因于专门清除羟基自由基。在速发型过敏反应中，氢不是通过其自由基清除活性，而是通过调节特定的信号传导途径发挥其有益作用。氢在其他疾病中的作用可能是通过调节尚未确定的信号通路来介导的。我们的研究还表明，氢是一种气体信号分子，如一氧化氮。(C)2009 Elsevier Inc. All rights reserved.
Molecular hydrogen ameliorates oxidative stress-associated diseases in animal models. We found that oral intake of hydrogen-rich water abolishes an immediate-type allergic reaction in mice. Using rat RBL-2H3 mast cells, we demonstrated that hydrogen attenuates phosphorylation of the Fc epsilon RI-associated Lyn and its downstream signal transduction, which subsequently inhibits the NADPH oxidase activity and reduces the generation of hydrogen peroxide. We also found that inhibition of NADPH oxidase attenuates phosphorylation of Lyn in mast cells, indicating the presence of a feed-forward loop that potentiates the allergic responses. Hydrogen accordingly inhibits all tested signaling molecule(s) in the loop. Hydrogen effects have been solely ascribed to exclusive removal of hydroxyl radical. In the immediate-type allergic reaction, hydrogen exerts its beneficial effect not by its radical scavenging activity but by modulating a specific signaling pathway. Effects of hydrogen in other diseases are possibly mediated by modulation of yet unidentified signaling pathways. Our studies also suggest that hydrogen is a gaseous signaling molecule like nitric oxide. (C) 2009 Elsevier Inc. All rights reserved.