Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways
Transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) occurs at high levels at damage sites of vascular endothelial cell layers and regulates the functions of vascular endothelial cells. Reactive sulfur species (RSS), such as cysteine persulfide, glutathione persulfide...
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MDPI AG
2021-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/21/11762 |
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| author | Musubu Takahashi Tomoya Fujie Tsuyoshi Nakano Takato Hara Yasuhiro Shinkai Ryoko Takasawa Yasushi Hara Yoshito Kumagai Chika Yamamoto Toshiyuki Kaji |
| author_facet | Musubu Takahashi Tomoya Fujie Tsuyoshi Nakano Takato Hara Yasuhiro Shinkai Ryoko Takasawa Yasushi Hara Yoshito Kumagai Chika Yamamoto Toshiyuki Kaji |
| author_sort | Musubu Takahashi |
| collection | DOAJ |
| description | Transforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) occurs at high levels at damage sites of vascular endothelial cell layers and regulates the functions of vascular endothelial cells. Reactive sulfur species (RSS), such as cysteine persulfide, glutathione persulfide, and hydrogen persulfide, are cytoprotective factors against electrophiles such as reactive oxygen species and heavy metals. Previously, we reported that sodium trisulfide, a sulfane sulfur donor, promotes vascular endothelial cell proliferation. The objective of the present study was to clarify the regulation and significance of RSS synthesis in vascular endothelial cells after exposure to TGF-β<sub>1</sub>. Bovine aortic endothelial cells in a culture system were treated with TGF-β<sub>1</sub> to assess the expression of intracellular RSS, the effect of RSS on cell proliferation in the presence of TGF-β<sub>1</sub>, induction of RSS-producing enzymes by TGF-β<sub>1</sub>, and intracellular signal pathways that mediate this induction. The results suggest that TGF-β<sub>1</sub> increased intracellular RSS levels to modulate its inhibitory effect on proliferation. The increased production of RSS, probably high-molecular-mass RSS, was due to the induction of cystathionine γ-lyase and cystathionine β-synthase, which are RSS-producing enzymes, and the induction was mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 pathways in vascular endothelial cells. TGF-β<sub>1</sub> regulates vascular endothelial cell functions such as proliferation and fibrinolytic activity; intracellular high-molecular-mass RSS, which are increased by TGF-β<sub>1</sub>, may modulate the regulation activity in vascular endothelial cells. |
| first_indexed | 2024-03-10T06:01:42Z |
| format | Article |
| id | doaj.art-71c25b141ccd4f8b81de3f5e659cdf80 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T06:01:42Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-71c25b141ccd4f8b81de3f5e659cdf802023-11-22T20:57:28ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-10-0122211176210.3390/ijms222111762Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 PathwaysMusubu Takahashi0Tomoya Fujie1Tsuyoshi Nakano2Takato Hara3Yasuhiro Shinkai4Ryoko Takasawa5Yasushi Hara6Yoshito Kumagai7Chika Yamamoto8Toshiyuki Kaji9Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, JapanEnvironmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanResearch Institute for Biomedical Sciences, Tokyo University of Science, 2669 Yamazaki, Noda 278-0022, JapanEnvironmental Biology Laboratory, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, JapanFaculty of Pharmaceutical Sciences, Toho University, 2-2-1 Miyama, Funabashi 274-8510, JapanFaculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda 278-8510, JapanTransforming growth factor-β<sub>1</sub> (TGF-β<sub>1</sub>) occurs at high levels at damage sites of vascular endothelial cell layers and regulates the functions of vascular endothelial cells. Reactive sulfur species (RSS), such as cysteine persulfide, glutathione persulfide, and hydrogen persulfide, are cytoprotective factors against electrophiles such as reactive oxygen species and heavy metals. Previously, we reported that sodium trisulfide, a sulfane sulfur donor, promotes vascular endothelial cell proliferation. The objective of the present study was to clarify the regulation and significance of RSS synthesis in vascular endothelial cells after exposure to TGF-β<sub>1</sub>. Bovine aortic endothelial cells in a culture system were treated with TGF-β<sub>1</sub> to assess the expression of intracellular RSS, the effect of RSS on cell proliferation in the presence of TGF-β<sub>1</sub>, induction of RSS-producing enzymes by TGF-β<sub>1</sub>, and intracellular signal pathways that mediate this induction. The results suggest that TGF-β<sub>1</sub> increased intracellular RSS levels to modulate its inhibitory effect on proliferation. The increased production of RSS, probably high-molecular-mass RSS, was due to the induction of cystathionine γ-lyase and cystathionine β-synthase, which are RSS-producing enzymes, and the induction was mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 pathways in vascular endothelial cells. TGF-β<sub>1</sub> regulates vascular endothelial cell functions such as proliferation and fibrinolytic activity; intracellular high-molecular-mass RSS, which are increased by TGF-β<sub>1</sub>, may modulate the regulation activity in vascular endothelial cells.https://www.mdpi.com/1422-0067/22/21/11762endothelial cellcystathionine γ-lyasecystathionine β-synthasetransforming growth factor-β<sub>1</sub>reactive sulfur species |
| spellingShingle | Musubu Takahashi Tomoya Fujie Tsuyoshi Nakano Takato Hara Yasuhiro Shinkai Ryoko Takasawa Yasushi Hara Yoshito Kumagai Chika Yamamoto Toshiyuki Kaji Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways International Journal of Molecular Sciences endothelial cell cystathionine γ-lyase cystathionine β-synthase transforming growth factor-β<sub>1</sub> reactive sulfur species |
| title | Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways |
| title_full | Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways |
| title_fullStr | Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways |
| title_full_unstemmed | Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways |
| title_short | Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-β<sub>1</sub>: Induction of Cystathionine γ-Lyase and Cystathionine β-Synthase Expression Mediated by the ALK5-Smad2/3/4 and ALK5-Smad2/3-ATF4 Pathways |
| title_sort | synthesis of reactive sulfur species in cultured vascular endothelial cells after exposure to tgf β sub 1 sub induction of cystathionine γ lyase and cystathionine β synthase expression mediated by the alk5 smad2 3 4 and alk5 smad2 3 atf4 pathways |
| topic | endothelial cell cystathionine γ-lyase cystathionine β-synthase transforming growth factor-β<sub>1</sub> reactive sulfur species |
| url | https://www.mdpi.com/1422-0067/22/21/11762 |
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