NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes

作者：Lin Chih Chung; Hsieh Hsi Lung; Shih Ruey Horng; Chi Pei Ling; Cheng Shin Ei; Chen Jin Chung; Yang Chuen Mao^*

来源：Cell Communication and Signaling, 2012, 10(1): 35.

DOI：10.1186/1478-811X-10-35

• Brain inflammation
• Astrocytes
• Bradykinin
• Matrix metalloproteinase-9
• NADPH oxidase
• Reactive oxygen species

Background: Matrix metalloproteinase-9 (MMP-9) plays a crucial role in pathological processes of brain inflammation, injury, and neurodegeneration. Moreover, bradykinin (BK) induces the expression of several inflammatory proteins in brain astrocytes. Recent studies have suggested that increased oxidative stress is implicated in the brain inflammation and injury. However, whether BK induced MMP-9 expression mediated through oxidative stress remains virtually unknown. Herein we investigated the role of redox signals in BK-induced MMP-9 expression in rat brain astrocytes (RBA-1 cells). %26lt;br%26gt;Results: In the study, we first demonstrated that reactive oxygen species (ROS) plays a crucial role in BK-induced MMP-9 expression in cultured brain astrocytes (in vitro) and animal brain tissue (in vivo) models. Next, BK-induced MMP-9 expression is mediated through a Ca2+-mediated PKC-a linking to p47(phox)/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (i.e. c-Fos and c-Jun), which bound to MMP-9 promoter region, and thereby turned on transcription of MMP-9 gene. Functionally, BK-induced MMP-9 expression enhanced astrocytic migration. %26lt;br%26gt;Conclusions: These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-a-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.

• 出版日期2012-11-23
• 单位长春大学