Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization
Background/Aims: Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-01-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/486918 |
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| author | Yang Yang Fangyuan Yin Qiyun Hang Xiaoliang Dong Jiao Chen Ling Li Peng Cao Zhimin Yin Lan Luo |
| author_facet | Yang Yang Fangyuan Yin Qiyun Hang Xiaoliang Dong Jiao Chen Ling Li Peng Cao Zhimin Yin Lan Luo |
| author_sort | Yang Yang |
| collection | DOAJ |
| description | Background/Aims: Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of vascular endothelial permeability. However, the mechanism maintaining endothelial cell barrier function against inflammatory stress is not fully understood. Glutathione S-transferase pi (GSTpi) exists in various types of cells and protects them against different stresses. In our previous study, GSTpi was found to act as a negative regulator of inflammatory responses. Methods: We used a Transwell permeability assay to test the influence of GSTpi and its transferase activity on the increase of endothelial permeability induced by tumor necrosis factor alpha (TNF-α). TNF-α-induced actin remodeling and the influence of GSTpi were observed by using laser confocal microscopy. Western blotting was used to test the influence of GSTpi on TNF-α-activated p38 mitogen-activated protein kinase (MAPK)/MK2/heat shock protein 27 (HSP27). Results: GSTpi reduced TNF-α-induced stress fiber formation and endothelial permeability increase by restraining actin cytoskeleton rearrangement, and this reduction was unrelated to its transferase activity. We found that GSTpi inhibited p38MAPK phosphorylation by directly binding p38 and influenced downstream substrate HSP27-induced actin remodeling. Conclusion: GSTpi inhibited TNF-α-induced actin remodeling, stress fiber formation and endothelial permeability increase by inhibiting the p38MAPK/HSP27 signaling pathway. |
| first_indexed | 2024-12-19T05:17:56Z |
| format | Article |
| id | doaj.art-5dcd035bf63a41f0919393d5362f3d0d |
| institution | Directory Open Access Journal |
| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-12-19T05:17:56Z |
| publishDate | 2018-01-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
| record_format | Article |
| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-5dcd035bf63a41f0919393d5362f3d0d2022-12-21T20:34:35ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-01-0145140641810.1159/000486918486918Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin PolymerizationYang YangFangyuan YinQiyun HangXiaoliang DongJiao ChenLing LiPeng CaoZhimin YinLan LuoBackground/Aims: Inflammation-induced injury of the endothelial barrier occurs in several pathological conditions, including atherosclerosis, ischemia, and sepsis. Endothelial cytoskeleton rearrangement is an important pathological mechanism by which inflammatory stimulation triggers an increase of vascular endothelial permeability. However, the mechanism maintaining endothelial cell barrier function against inflammatory stress is not fully understood. Glutathione S-transferase pi (GSTpi) exists in various types of cells and protects them against different stresses. In our previous study, GSTpi was found to act as a negative regulator of inflammatory responses. Methods: We used a Transwell permeability assay to test the influence of GSTpi and its transferase activity on the increase of endothelial permeability induced by tumor necrosis factor alpha (TNF-α). TNF-α-induced actin remodeling and the influence of GSTpi were observed by using laser confocal microscopy. Western blotting was used to test the influence of GSTpi on TNF-α-activated p38 mitogen-activated protein kinase (MAPK)/MK2/heat shock protein 27 (HSP27). Results: GSTpi reduced TNF-α-induced stress fiber formation and endothelial permeability increase by restraining actin cytoskeleton rearrangement, and this reduction was unrelated to its transferase activity. We found that GSTpi inhibited p38MAPK phosphorylation by directly binding p38 and influenced downstream substrate HSP27-induced actin remodeling. Conclusion: GSTpi inhibited TNF-α-induced actin remodeling, stress fiber formation and endothelial permeability increase by inhibiting the p38MAPK/HSP27 signaling pathway.https://www.karger.com/Article/FullText/486918Glutathione S-transferase pi (GSTpi)Vascular permeabilityTumor necrosis factor alpha (TNF-α)F-actin remodelingP38MAPK/HSP27 signaling pathway |
| spellingShingle | Yang Yang Fangyuan Yin Qiyun Hang Xiaoliang Dong Jiao Chen Ling Li Peng Cao Zhimin Yin Lan Luo Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization Cellular Physiology and Biochemistry Glutathione S-transferase pi (GSTpi) Vascular permeability Tumor necrosis factor alpha (TNF-α) F-actin remodeling P38MAPK/HSP27 signaling pathway |
| title | Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization |
| title_full | Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization |
| title_fullStr | Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization |
| title_full_unstemmed | Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization |
| title_short | Regulation of Endothelial Permeability by Glutathione S-Transferase Pi Against Actin Polymerization |
| title_sort | regulation of endothelial permeability by glutathione s transferase pi against actin polymerization |
| topic | Glutathione S-transferase pi (GSTpi) Vascular permeability Tumor necrosis factor alpha (TNF-α) F-actin remodeling P38MAPK/HSP27 signaling pathway |
| url | https://www.karger.com/Article/FullText/486918 |
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