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

作　　者：Wenjun Liu Hailong Wu Lili Chen Yankai Wen Xiaoni Kong Wei-Qiang Gao 

机构地区：[1]State Key Laboratory for Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital,School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China

出　　处：《Cell Research》2015年第6期691-706,共16页细胞研究（英文版）

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 （autosomai recessive, early onset） 7 （Park7） has a cytoprotective role by eliminating ROS. However, wheth- er 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 produc- tion 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, NA- DPH oxidase activation and inflammation responses.

关 键 词：Park7 INFLAMMATION SEPSIS NADPH oxidase 

分 类 号：Q255[生物学—细胞生物学] S432.23[农业科学—植物病理学]