Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells
Clinical data implicate fluctuations of high levels of plasma glucose in cardiovascular diseases. Endothelial cells (EC) are the first cells of the vessel wall exposed to them. Our aim was to evaluate the effects of oscillating glucose (OG) on EC function and to decipher new molecular mechanisms inv...
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| Format: | Article |
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MDPI AG
2023-03-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/13/4/626 |
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| author | Laura Toma Gabriela M. Sanda Camelia S. Stancu Loredan S. Niculescu Mina Raileanu Anca V. Sima |
| author_facet | Laura Toma Gabriela M. Sanda Camelia S. Stancu Loredan S. Niculescu Mina Raileanu Anca V. Sima |
| author_sort | Laura Toma |
| collection | DOAJ |
| description | Clinical data implicate fluctuations of high levels of plasma glucose in cardiovascular diseases. Endothelial cells (EC) are the first cells of the vessel wall exposed to them. Our aim was to evaluate the effects of oscillating glucose (OG) on EC function and to decipher new molecular mechanisms involved. Cultured human ECs (EA.hy926 line and primary cells) were exposed to OG (5/25 mM alternatively at 3 h), constant HG (25 mM) or physiological concentration (5 mM, NG) for 72 h. Markers of inflammation (Ninj-1, MCP-1, RAGE, TNFR1, NF-kB, and p38 MAPK), oxidative stress (ROS, VPO1, and HO-1), and transendothelial transport proteins (SR-BI, caveolin-1, and VAMP-3) were assessed. Inhibitors of ROS (NAC), NF-kB (Bay 11-7085), and Ninj-1 silencing were used to identify the mechanisms of OG-induced EC dysfunction. The results revealed that OG determined an increased expression of Ninj-1, MCP-1, RAGE, TNFR1, SR-B1, and VAMP-3 andstimulated monocyte adhesion. All of these effects were induced bymechanisms involving ROS production or NF-kB activation. <i>NINJ-1</i> silencing inhibited the upregulation of caveolin-1 and VAMP-3 induced by OG in EC. In conclusion, OG induces increased inflammatory stress, ROS production, and NF-kB activation and stimulates transendothelial transport. To this end, we propose a novel mechanism linking Ninj-1 up-regulation to increased expression of transendothelial transport proteins. |
| first_indexed | 2024-03-11T05:12:04Z |
| format | Article |
| id | doaj.art-7d12c573890d44648974e8f753d47738 |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-03-11T05:12:04Z |
| publishDate | 2023-03-01 |
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| series | Biomolecules |
| spelling | doaj.art-7d12c573890d44648974e8f753d477382023-11-17T18:29:07ZengMDPI AGBiomolecules2218-273X2023-03-0113462610.3390/biom13040626Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial CellsLaura Toma0Gabriela M. Sanda1Camelia S. Stancu2Loredan S. Niculescu3Mina Raileanu4Anca V. Sima5Lipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaLipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaLipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaLipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaLipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaLipidomics Department, Institute of Cellular Biology and Pathology “Nicolae Simionescu” of the Romanian Academy, 8, B.P. Hasdeu Street, 050568 Bucharest, RomaniaClinical data implicate fluctuations of high levels of plasma glucose in cardiovascular diseases. Endothelial cells (EC) are the first cells of the vessel wall exposed to them. Our aim was to evaluate the effects of oscillating glucose (OG) on EC function and to decipher new molecular mechanisms involved. Cultured human ECs (EA.hy926 line and primary cells) were exposed to OG (5/25 mM alternatively at 3 h), constant HG (25 mM) or physiological concentration (5 mM, NG) for 72 h. Markers of inflammation (Ninj-1, MCP-1, RAGE, TNFR1, NF-kB, and p38 MAPK), oxidative stress (ROS, VPO1, and HO-1), and transendothelial transport proteins (SR-BI, caveolin-1, and VAMP-3) were assessed. Inhibitors of ROS (NAC), NF-kB (Bay 11-7085), and Ninj-1 silencing were used to identify the mechanisms of OG-induced EC dysfunction. The results revealed that OG determined an increased expression of Ninj-1, MCP-1, RAGE, TNFR1, SR-B1, and VAMP-3 andstimulated monocyte adhesion. All of these effects were induced bymechanisms involving ROS production or NF-kB activation. <i>NINJ-1</i> silencing inhibited the upregulation of caveolin-1 and VAMP-3 induced by OG in EC. In conclusion, OG induces increased inflammatory stress, ROS production, and NF-kB activation and stimulates transendothelial transport. To this end, we propose a novel mechanism linking Ninj-1 up-regulation to increased expression of transendothelial transport proteins.https://www.mdpi.com/2218-273X/13/4/626endothelial cell dysfunctioninflammatory stressoscillating glucoseoxidative stressNinjurin-1transendothelial transport proteins |
| spellingShingle | Laura Toma Gabriela M. Sanda Camelia S. Stancu Loredan S. Niculescu Mina Raileanu Anca V. Sima Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells Biomolecules endothelial cell dysfunction inflammatory stress oscillating glucose oxidative stress Ninjurin-1 transendothelial transport proteins |
| title | Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells |
| title_full | Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells |
| title_fullStr | Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells |
| title_full_unstemmed | Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells |
| title_short | Oscillating Glucose Induces the Increase in Inflammatory Stress through Ninjurin-1 Up-Regulation and Stimulation of Transport Proteins in Human Endothelial Cells |
| title_sort | oscillating glucose induces the increase in inflammatory stress through ninjurin 1 up regulation and stimulation of transport proteins in human endothelial cells |
| topic | endothelial cell dysfunction inflammatory stress oscillating glucose oxidative stress Ninjurin-1 transendothelial transport proteins |
| url | https://www.mdpi.com/2218-273X/13/4/626 |
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