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Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells
Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-...
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| Published in: | Journal of biomedical science 2009-01, Vol.16 (1), p.12-12 |
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| container_title | Journal of biomedical science |
| container_volume | 16 |
| creator | Hsieh, Chung-Yu Hsiao, Huai-Yu Wu, Wan-Yi Liu, Ching-Ann Tsai, Yu-Chih Chao, Yuen-Jen Wang, Danny L Hsieh, Hsyue-Jen |
| description | Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.
Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm2) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.
Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system. |
| doi_str_mv | 10.1186/1423-0127-16-12 |
| format | article |
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Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm2) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.
Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</description><identifier>ISSN: 1423-0127</identifier><identifier>ISSN: 1021-7770</identifier><identifier>EISSN: 1423-0127</identifier><identifier>DOI: 10.1186/1423-0127-16-12</identifier><identifier>PMID: 19272177</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Active Transport, Cell Nucleus - physiology ; Cell Nucleus - metabolism ; Cells, Cultured ; Endothelial Cells - cytology ; Endothelial Cells - metabolism ; Enzyme Inhibitors - metabolism ; Gene Expression Regulation ; Heme Oxygenase-1 - genetics ; Heme Oxygenase-1 - metabolism ; Humans ; Hydrogen Peroxide - metabolism ; NF-E2-Related Factor 2 - genetics ; NF-E2-Related Factor 2 - metabolism ; Nitric Oxide Synthase - antagonists & inhibitors ; Nitric Oxide Synthase - metabolism ; Oxidants - metabolism ; Phosphatidylinositol 3-Kinases - metabolism ; Reactive Oxygen Species - metabolism ; Shear Strength ; Stress, Mechanical</subject><ispartof>Journal of biomedical science, 2009-01, Vol.16 (1), p.12-12</ispartof><rights>Copyright © 2009 Hsieh et al; licensee BioMed Central Ltd. 2009 Hsieh et al; licensee BioMed Central Ltd.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b582t-f1fd81ae5944071c741ca5fc663c7d44b60d7d6a6471de1f736b3554fc9b33bc3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653516/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653516/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,730,783,787,888,27938,27939,53806,53808</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19272177$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hsieh, Chung-Yu</creatorcontrib><creatorcontrib>Hsiao, Huai-Yu</creatorcontrib><creatorcontrib>Wu, Wan-Yi</creatorcontrib><creatorcontrib>Liu, Ching-Ann</creatorcontrib><creatorcontrib>Tsai, Yu-Chih</creatorcontrib><creatorcontrib>Chao, Yuen-Jen</creatorcontrib><creatorcontrib>Wang, Danny L</creatorcontrib><creatorcontrib>Hsieh, Hsyue-Jen</creatorcontrib><title>Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells</title><title>Journal of biomedical science</title><addtitle>J Biomed Sci</addtitle><description>Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.
Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm2) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.
Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</description><subject>Active Transport, Cell Nucleus - physiology</subject><subject>Cell Nucleus - metabolism</subject><subject>Cells, Cultured</subject><subject>Endothelial Cells - cytology</subject><subject>Endothelial Cells - metabolism</subject><subject>Enzyme Inhibitors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>Heme Oxygenase-1 - genetics</subject><subject>Heme Oxygenase-1 - metabolism</subject><subject>Humans</subject><subject>Hydrogen Peroxide - metabolism</subject><subject>NF-E2-Related Factor 2 - genetics</subject><subject>NF-E2-Related Factor 2 - metabolism</subject><subject>Nitric Oxide Synthase - antagonists & inhibitors</subject><subject>Nitric Oxide Synthase - metabolism</subject><subject>Oxidants - metabolism</subject><subject>Phosphatidylinositol 3-Kinases - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Shear Strength</subject><subject>Stress, Mechanical</subject><issn>1423-0127</issn><issn>1021-7770</issn><issn>1423-0127</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNp1kltLxDAQhYMo3p99k_6Bup1c2xdBxRuIguhzyHU3km2WtCv47-1aWV3QpyRzznzMcILQCVRnADWfAMWkrACLEngJeAvtryvbv-576KDr3qoKWFOLXbQHDRYYhNhH02c3XUbVh9QWyRfdzKlchtYujbNFuzRxeBd9Vm0Xk1nb-pkrHrPHo2JyWHwpXpk-5SK0hWttGkwxqFgYF2N3hHa8ip07_j4P0evN9cvVXfnwdHt_dfFQalbjvvTgbQ3KsYbSSoARFIxi3nBOjLCUal5ZYbniVIB14AXhmjBGvWk0IdqQQ3Q_cm1Sb3KRw1zlD5lUkF-FlKdS5T4Me0nOoDZYawKeU-8a3XhBa0I5t7wRpB5Y5yNrsdRzZ41rh3XjBnRTacNMTtO7xJwRBnwAXI4AHdI_gE3FpLlchSZXoUngEvAAmYwQk1PXZefX_VDJ1Sf4o-P099w__u_UySeTAq-E</recordid><startdate>20090122</startdate><enddate>20090122</enddate><creator>Hsieh, Chung-Yu</creator><creator>Hsiao, Huai-Yu</creator><creator>Wu, Wan-Yi</creator><creator>Liu, Ching-Ann</creator><creator>Tsai, Yu-Chih</creator><creator>Chao, Yuen-Jen</creator><creator>Wang, Danny L</creator><creator>Hsieh, Hsyue-Jen</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><general>BMC</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20090122</creationdate><title>Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells</title><author>Hsieh, Chung-Yu ; Hsiao, Huai-Yu ; Wu, Wan-Yi ; Liu, Ching-Ann ; Tsai, Yu-Chih ; Chao, Yuen-Jen ; Wang, Danny L ; Hsieh, Hsyue-Jen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b582t-f1fd81ae5944071c741ca5fc663c7d44b60d7d6a6471de1f736b3554fc9b33bc3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Active Transport, Cell Nucleus - physiology</topic><topic>Cell Nucleus - metabolism</topic><topic>Cells, Cultured</topic><topic>Endothelial Cells - cytology</topic><topic>Endothelial Cells - metabolism</topic><topic>Enzyme Inhibitors - metabolism</topic><topic>Gene Expression Regulation</topic><topic>Heme Oxygenase-1 - genetics</topic><topic>Heme Oxygenase-1 - metabolism</topic><topic>Humans</topic><topic>Hydrogen Peroxide - metabolism</topic><topic>NF-E2-Related Factor 2 - genetics</topic><topic>NF-E2-Related Factor 2 - metabolism</topic><topic>Nitric Oxide Synthase - antagonists & inhibitors</topic><topic>Nitric Oxide Synthase - metabolism</topic><topic>Oxidants - metabolism</topic><topic>Phosphatidylinositol 3-Kinases - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Shear Strength</topic><topic>Stress, Mechanical</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hsieh, Chung-Yu</creatorcontrib><creatorcontrib>Hsiao, Huai-Yu</creatorcontrib><creatorcontrib>Wu, Wan-Yi</creatorcontrib><creatorcontrib>Liu, Ching-Ann</creatorcontrib><creatorcontrib>Tsai, Yu-Chih</creatorcontrib><creatorcontrib>Chao, Yuen-Jen</creatorcontrib><creatorcontrib>Wang, Danny L</creatorcontrib><creatorcontrib>Hsieh, Hsyue-Jen</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>Open Access: DOAJ - Directory of Open Access Journals</collection><jtitle>Journal of biomedical science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hsieh, Chung-Yu</au><au>Hsiao, Huai-Yu</au><au>Wu, Wan-Yi</au><au>Liu, Ching-Ann</au><au>Tsai, Yu-Chih</au><au>Chao, Yuen-Jen</au><au>Wang, Danny L</au><au>Hsieh, Hsyue-Jen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells</atitle><jtitle>Journal of biomedical science</jtitle><addtitle>J Biomed Sci</addtitle><date>2009-01-22</date><risdate>2009</risdate><volume>16</volume><issue>1</issue><spage>12</spage><epage>12</epage><pages>12-12</pages><issn>1423-0127</issn><issn>1021-7770</issn><eissn>1423-0127</eissn><abstract>Vascular endothelial cells (ECs) constantly experience fluid shear stresses generated by blood flow. Laminar flow is known to produce atheroprotective effects on ECs. Nrf2 is a transcription factor that is essential for the antioxidant response element (ARE)-mediated induction of genes such as heme-oxygenase 1 (HO-1). We previously showed that fluid shear stress increases intracellular reactive oxygen species (ROS) in ECs. Moreover, oxidants are known to stimulate Nrf2. We thus examined the regulation of Nrf2 in cultured human ECs by shear stress.
Exposure of human umbilical vein endothelial cells (HUVECs) to laminar shear stress (12 dyne/cm2) induced Nrf2 nuclear translocation, which was inhibited by a phosphatidylinositol 3-kinase (PI3K) inhibitor, a protein kinase C (PKC) inhibitor, and an antioxidant agent N-acetyl cysteine (NAC), but not by other protein kinase inhibitors. Therefore, PI3K, PKC, and ROS are involved in the signaling pathway that leads to the shear-induced nuclear translocation of Nrf2. We also found that shear stress increased the ARE-binding activity of Nrf2 and the downstream expression of HO-1.
Our data suggest that the atheroprotective effect of laminar flow is partially attributed to Nrf2 activation which results in ARE-mediated gene transcriptions, such as HO-1 expression, that are beneficial to the cardiovascular system.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>19272177</pmid><doi>10.1186/1423-0127-16-12</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| source | Open Access: PubMed Central; Publicly Available Content Database |
| subjects | Active Transport, Cell Nucleus - physiology Cell Nucleus - metabolism Cells, Cultured Endothelial Cells - cytology Endothelial Cells - metabolism Enzyme Inhibitors - metabolism Gene Expression Regulation Heme Oxygenase-1 - genetics Heme Oxygenase-1 - metabolism Humans Hydrogen Peroxide - metabolism NF-E2-Related Factor 2 - genetics NF-E2-Related Factor 2 - metabolism Nitric Oxide Synthase - antagonists & inhibitors Nitric Oxide Synthase - metabolism Oxidants - metabolism Phosphatidylinositol 3-Kinases - metabolism Reactive Oxygen Species - metabolism Shear Strength Stress, Mechanical |
| title | Regulation of shear-induced nuclear translocation of the Nrf2 transcription factor in endothelial cells |
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