SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression
Background: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular ef...
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| Format: | Article |
| Language: | English |
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Cell Physiol Biochem Press GmbH & Co KG
2015-01-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | http://www.karger.com/Article/FullText/369671 |
| _version_ | 1818681369463619584 |
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| author | Ping Xie Yingchun Duan Xianzhi Guo Lina Hu Minghua Yu |
| author_facet | Ping Xie Yingchun Duan Xianzhi Guo Lina Hu Minghua Yu |
| author_sort | Ping Xie |
| collection | DOAJ |
| description | Background: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. Conclusion: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression. |
| first_indexed | 2024-12-17T10:01:51Z |
| format | Article |
| id | doaj.art-ecaf7c5c9ebf441793df5f1f76f2dbf7 |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-17T10:01:51Z |
| publishDate | 2015-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-ecaf7c5c9ebf441793df5f1f76f2dbf72022-12-21T21:53:16ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782015-01-01351172810.1159/000369671369671SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor ExpressionPing XieYingchun DuanXianzhi GuoLina HuMinghua YuBackground: Salvianolic acid A (SalA) has been shown to display robust protection against endothelial injury. VLDL receptor (VLDLr) is expressed at high levels in the endothelial cells. However its endothelial biological function has not been completely elucidated. Here, we investigated molecular effects of SalA on endothelial VLDLr expression, ER stress, and apoptosis under hypoxia condition. Methods: Human umbilical vein endothelial cells (HUVECs) pretreated with SalA were subjected to hypoxia stimulation. Endothelial ER stress and apoptosis were examined. The mRNA levels were tested by real-time RT-PCR, and the protein levels were determined by immunoblot analysis. Results: Pretreatment of HUVECs with SalA markedly attenuated hypoxia-induced endothelial ER stress and apoptosis. Hypoxia resulted in enhancement of VLDLr expression, which was effectively inhibited by SalA pretreatment. Furthermore, luciferase reporter gene assays indicated that SalA inhibited vldlr gene promoter activity, and ChIP assays showed that hypoxia increase the recruitment of HIF-1α to the vldlr gene promoter, and this process was hampered markedly by pretreatment of SalA. Finally, overexpression of VLDLr abolished SalA-mediated protection of endothelial cells from ER stress and apoptosis. Knockdown of VLDLr mimicked SalA protective effect. Conclusion: These results for the first time demonstrate that SalA protects against hypoxia-induced endothelial ER stress and apoptosis through inhibiting recruitment of HIF-1α to vldlr gene promoter and thus suppressing VLDLr expression.http://www.karger.com/Article/FullText/369671ApoptosisSalvianolic acid AHypoxiaVLDL receptorEndothelial endoplasmic reticulum stress |
| spellingShingle | Ping Xie Yingchun Duan Xianzhi Guo Lina Hu Minghua Yu SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression Cellular Physiology and Biochemistry Apoptosis Salvianolic acid A Hypoxia VLDL receptor Endothelial endoplasmic reticulum stress |
| title | SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression |
| title_full | SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression |
| title_fullStr | SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression |
| title_full_unstemmed | SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression |
| title_short | SalA Attenuates Hypoxia-Induced Endothelial Endoplasmic Reticulum Stress and Apoptosis via Down-Regulation of VLDL Receptor Expression |
| title_sort | sala attenuates hypoxia induced endothelial endoplasmic reticulum stress and apoptosis via down regulation of vldl receptor expression |
| topic | Apoptosis Salvianolic acid A Hypoxia VLDL receptor Endothelial endoplasmic reticulum stress |
| url | http://www.karger.com/Article/FullText/369671 |
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