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Cell Research:Park7与NADPH亚基相互作用,指导其ROS生产并对抗脓毒症

标签:Park7 NADPH
摘要 : 上海交大生物医学工程学院的研究团队发现,Park7(帕金森病蛋白7)能够与NADPH氧化酶的亚基相互作用,指导其ROS生产并对抗脓毒症。这项研究发表在五月二十九日的Cell Research杂志上,文章的通讯作者是高维强(Wei-Qiang Gao)教授和孔晓妮(Xiaoni Kong)研究员。

 脓毒症(sepsis)是指由于创伤、感染等一系列因素导致机体产生过激的炎症反应,会对机体产生严重的危害,是临床危重患者的主要死亡原因之一。这种疾病死亡率高而且发病机制复杂,一直是全世界重症医学研究的难点和热点。在脓毒症的病理过程中,免疫系统的功能抑制是一个非常突出问题。

已知NADPH氧化酶生产的活性氧(ROS)会通过Toll样受体(TLR)调节脓毒症中的炎症应答。上海交大生物医学工程学院的研究团队发现,Park7(帕金森病蛋白7)能够与NADPH氧化酶的亚基相互作用,指导其ROS生产并对抗脓毒症。这项研究发表在五月二十九日的Cell Research杂志上,文章的通讯作者是高维强(Wei-Qiang Gao)教授和孔晓妮(Xiaoni Kong)研究员。

研究人员发现,与野生型小鼠相比,Park7−/−小鼠在脓毒症中的死亡率和细菌负荷明显增加,系统性炎症和局部炎症显著减少,巨噬细胞的吞噬作用和杀菌能力严重受损。

令人惊讶的是,在Park7−/−巨噬细胞和Park7缺陷型RAW264.7细胞中,LPS和佛波酯PMA(phorbol-12-myristate-13-acetate)刺激不能诱导ROS和促炎症的细胞因子生产。

进一步研究表明,Park7通过自己的C端结合p47phox(一个NADPH氧化酶的亚基),促进依赖NADPH氧化酶的ROS生产。恢复Park7的表达可以挽救ROS生产,在LPS诱导的脓毒症中改善小鼠的生存情况。

这项研究向人们展示,Park7具有对抗脓毒症的保护性作用,通过控制巨噬细胞激活、NADPH氧化酶激活和炎症应答起作用。

原文标题:Park7 interacts with p47phox to direct NADPH oxidase-dependent ROS production and protect against sepsis

原文摘要:Inappropriate inflammation responses contribute to mortality during sepsis. Through Toll-like receptors (TLRs), reactive oxygen species (ROS) produced by NADPH oxidase could modulate the inflammation responses. Parkinson disease (autosomal recessive, early onset) 7 (Park7) has a cytoprotective role by eliminating ROS. However, whether Park7 could modulate inflammation responses and mortality in sepsis is unclear. Here, we show that, compared with wild-type mice, Park7−/− mice had significantly increased mortality and bacterial burdens in sepsis model along with markedly decreased systemic and local inflammation, and drastically impaired macrophage phagocytosis and bacterial killing abilities. Surprisingly, LPS and phorbol-12-myristate-13-acetate stimulation failed to induce ROS and proinflammatory cytokine production in Park7−/− macrophages and Park7-deficient RAW264.7 cells. Through its C-terminus, Park7 binds to p47phox, a subunit of the NADPH oxidase, to promote NADPH oxidase-dependent production of ROS. Restoration of Park7 expression rescues ROS production and improves survival in LPS-induced sepsis. Together, our study shows that Park7 has a protective role against sepsis by controlling macrophage activation, NADPH oxidase activation and inflammation responses.

来源: Cell Research 浏览次数:0

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