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

التفاصيل البيبلوغرافية
العنوان: NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes
المؤلفون: Lin, Chih-Chung, Hsieh, Hsi-Lung, Shih, Ruey-Horng, Chi, Pei-Ling, Cheng, Shin-Ei, Chen, Jin-Chung, Yang, Chuen-Mao
بيانات النشر: BioMed Central Ltd.
سنة النشر: 2012
المجموعة: BioMed Central
مصطلحات موضوعية: Brain inflammation, Astrocytes, Bradykinin, Matrix metalloproteinase-9, NADPH oxidase, Reactive oxygen species
الوصف: 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). 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 Ca 2+ -mediated PKC-α 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. Conclusions These results demonstrated that in RBA-1 cells, activation of AP-1 (c-Fos/c-Jun) by the PKC-α-mediated Nox2/ROS signals is essential for up-regulation of MMP-9 and cell migration enhanced by BK.
نوع الوثيقة: report
اللغة: English
العلاقة: http://www.biosignaling.com/content/10/1/35Test
الإتاحة: http://www.biosignaling.com/content/10/1/35Test
حقوق: Copyright 2012 Lin et al.; licensee BioMed Central Ltd.
رقم الانضمام: edsbas.CEBE4D73
قاعدة البيانات: BASE