The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin.
SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4032329?pdf=render |
| _version_ | 1828515084064784384 |
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| author | Yu-Yan Jia Jie Lu Yue Huang Guang Liu Peng Gao Yan-Zhen Wan Ran Zhang Zhu-Qin Zhang Rui-Feng Yang Xiaoqiang Tang Jing Xu Xu Wang Hou-Zao Chen De-Pei Liu |
| author_facet | Yu-Yan Jia Jie Lu Yue Huang Guang Liu Peng Gao Yan-Zhen Wan Ran Zhang Zhu-Qin Zhang Rui-Feng Yang Xiaoqiang Tang Jing Xu Xu Wang Hou-Zao Chen De-Pei Liu |
| author_sort | Yu-Yan Jia |
| collection | DOAJ |
| description | SIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis. |
| first_indexed | 2024-12-11T18:08:27Z |
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| id | doaj.art-f890f5eaba6a4ec7acfd54ea0338114a |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-11T18:08:27Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f890f5eaba6a4ec7acfd54ea0338114a2022-12-22T00:55:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0195e9799910.1371/journal.pone.0097999The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin.Yu-Yan JiaJie LuYue HuangGuang LiuPeng GaoYan-Zhen WanRan ZhangZhu-Qin ZhangRui-Feng YangXiaoqiang TangJing XuXu WangHou-Zao ChenDe-Pei LiuSIRT1, a class III histone deacetylase, acts as a negative regulator for many transcription factors, and plays protective roles in inflammation and atherosclerosis. Transcription factor nuclear factor of activated T cells (NFAT) has been previously shown to play pro-inflammatory roles in endothelial cells. Inhibition of NFAT signaling may be an attractive target to regulate inflammation in atherosclerosis. However, whether NFAT transcriptional activity is suppressed by SIRT1 remains unknown. In this study, we found that SIRT1 suppressed NFAT-mediated transcriptional activity. SIRT1 interacted with NFAT, and the NHR and RHR domains of NFAT mediated the interaction with SIRT1. Moreover, we found that SIRT1 primarily deacetylated NFATc3. Adenoviral over-expression of SIRT1 suppressed PMA and calcium ionophore Ionomycin (PMA/Io)-induced COX-2 expression in human umbilical vein endothelial cells (HUVECs), while SIRT1 RNAi reversed the effects in HUVECs. Moreover, inhibition of COX-2 expression by SIRT1 in PMA/Io-treated HUVECs was largely abrogated by inhibiting NFAT activation. Furthermore, SIRT1 inhibited NFAT-induced COX-2 promoter activity, and reduced NFAT binding to the COX-2 promoter in PMA/Io-treated HUVECs. These results suggest that suppression of NFAT transcriptional activity is involved in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Io, and that the negative regulatory mechanisms of NFAT by SIRT1 may contribute to its anti-inflammatory effects in atherosclerosis.http://europepmc.org/articles/PMC4032329?pdf=render |
| spellingShingle | Yu-Yan Jia Jie Lu Yue Huang Guang Liu Peng Gao Yan-Zhen Wan Ran Zhang Zhu-Qin Zhang Rui-Feng Yang Xiaoqiang Tang Jing Xu Xu Wang Hou-Zao Chen De-Pei Liu The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. PLoS ONE |
| title | The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. |
| title_full | The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. |
| title_fullStr | The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. |
| title_full_unstemmed | The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. |
| title_short | The involvement of NFAT transcriptional activity suppression in SIRT1-mediated inhibition of COX-2 expression induced by PMA/Ionomycin. |
| title_sort | involvement of nfat transcriptional activity suppression in sirt1 mediated inhibition of cox 2 expression induced by pma ionomycin |
| url | http://europepmc.org/articles/PMC4032329?pdf=render |
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