NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes
<p>Abstract</p> <p>Background</p> <p>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 astroc...
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| Format: | Article |
| Language: | English |
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BMC
2012-11-01
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| Series: | Cell Communication and Signaling |
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| Online Access: | http://www.biosignaling.com/content/10/1/35 |
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| author | Lin Chih-Chung Hsieh Hsi-Lung Shih Ruey-Horng Chi Pei-Ling Cheng Shin-Ei Chen Jin-Chung Yang Chuen-Mao |
| author_facet | Lin Chih-Chung Hsieh Hsi-Lung Shih Ruey-Horng Chi Pei-Ling Cheng Shin-Ei Chen Jin-Chung Yang Chuen-Mao |
| author_sort | Lin Chih-Chung |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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 (<it>in vitro</it>) and animal brain tissue (<it>in vivo</it>) models. Next, BK-induced MMP-9 expression is mediated through a Ca<sup>2+</sup>-mediated PKC-α linking to p47<sup>phox</sup>/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (<it>i.e.</it> 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.</p> <p>Conclusions</p> <p>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.</p> |
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| format | Article |
| id | doaj.art-6f5b24856c0348d5a13b9053c7cef0cf |
| institution | Directory Open Access Journal |
| issn | 1478-811X |
| language | English |
| last_indexed | 2024-04-13T12:17:12Z |
| publishDate | 2012-11-01 |
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| series | Cell Communication and Signaling |
| spelling | doaj.art-6f5b24856c0348d5a13b9053c7cef0cf2022-12-22T02:47:20ZengBMCCell Communication and Signaling1478-811X2012-11-011013510.1186/1478-811X-10-35NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytesLin Chih-ChungHsieh Hsi-LungShih Ruey-HorngChi Pei-LingCheng Shin-EiChen Jin-ChungYang Chuen-Mao<p>Abstract</p> <p>Background</p> <p>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).</p> <p>Results</p> <p>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 (<it>in vitro</it>) and animal brain tissue (<it>in vivo</it>) models. Next, BK-induced MMP-9 expression is mediated through a Ca<sup>2+</sup>-mediated PKC-α linking to p47<sup>phox</sup>/NADPH oxidase 2 (Nox2)/ROS signaling pathway. Nox2-dependent ROS generation led to activation and up-regulation of the downstream transcriptional factor AP-1 (<it>i.e.</it> 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.</p> <p>Conclusions</p> <p>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.</p>http://www.biosignaling.com/content/10/1/35Brain inflammationAstrocytesBradykininMatrix metalloproteinase-9NADPH oxidaseReactive oxygen species |
| spellingShingle | Lin Chih-Chung Hsieh Hsi-Lung Shih Ruey-Horng Chi Pei-Ling Cheng Shin-Ei Chen Jin-Chung Yang Chuen-Mao NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes Cell Communication and Signaling Brain inflammation Astrocytes Bradykinin Matrix metalloproteinase-9 NADPH oxidase Reactive oxygen species |
| title | NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes |
| title_full | NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes |
| title_fullStr | NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes |
| title_full_unstemmed | NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes |
| title_short | NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes |
| title_sort | nadph oxidase 2 derived reactive oxygen species signal contributes to bradykinin induced matrix metalloproteinase 9 expression and cell migration in brain astrocytes |
| topic | Brain inflammation Astrocytes Bradykinin Matrix metalloproteinase-9 NADPH oxidase Reactive oxygen species |
| url | http://www.biosignaling.com/content/10/1/35 |
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