Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury
Tanshinone IIA (Tan IIA), an active ingredient of Danshen, is a well-used drug to treat cardiovascular diseases. Currently, the mechanisms involved remain poorly understood. Given that many actions of Tan IIA could be similarly achieved by hydrogen sulfide (H<sub>2</sub>S), we speculated...
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MDPI AG
2021-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/7/1007 |
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| author | Qiaojing Yan Zhimin Mao Jingru Hong Kun Gao Manabu Niimi Takahiko Mitsui Jian Yao |
| author_facet | Qiaojing Yan Zhimin Mao Jingru Hong Kun Gao Manabu Niimi Takahiko Mitsui Jian Yao |
| author_sort | Qiaojing Yan |
| collection | DOAJ |
| description | Tanshinone IIA (Tan IIA), an active ingredient of Danshen, is a well-used drug to treat cardiovascular diseases. Currently, the mechanisms involved remain poorly understood. Given that many actions of Tan IIA could be similarly achieved by hydrogen sulfide (H<sub>2</sub>S), we speculated that Tan IIA might work through the induction of endogenous H<sub>2</sub>S. This study was to test this hypothesis. Exposure to endothelial cells to Tan IIA elevated H<sub>2</sub>S-synthesizing enzyme cystathionine γ-Lyase (CSE), associated with an increased level of endogenous H<sub>2</sub>S and free thiol activity. Further analysis revealed that this effect of Tan IIA was mediated by an estrogen receptor (ER) and cAMP signaling pathway. It stimulated VASP and CREB phosphorylation. Inhibition of ER or PKA abolished the CSE-elevating effect, whereas activation of ER or PKA mimicked the effect of Tan IIA. In an oxidative endothelial cell injury model, Tan IIA potently attenuated oxidative stress and inhibited cell death. In support of a role of endogenous H<sub>2</sub>S, inhibition of CSE aggerated oxidative cell injury. On the contrary, supplement of H<sub>2</sub>S attenuated cell injury. Collectively, our study characterized endogenous H<sub>2</sub>S as a novel mediator underlying the pharmacological actions of Tan IIA. Given the multifaceted functions of H<sub>2</sub>S, the H<sub>2</sub>S-stimulating property of Tan IIA could be exploited for treating many diseases. |
| first_indexed | 2024-03-10T10:08:00Z |
| format | Article |
| id | doaj.art-e9fe0e9d70394694a1c3018ff5410efd |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T10:08:00Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-e9fe0e9d70394694a1c3018ff5410efd2023-11-22T01:24:10ZengMDPI AGAntioxidants2076-39212021-06-01107100710.3390/antiox10071007Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative InjuryQiaojing Yan0Zhimin Mao1Jingru Hong2Kun Gao3Manabu Niimi4Takahiko Mitsui5Jian Yao6Division of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanDivision of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanDivision of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanDivision of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanDivision of Molecular Pathology, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanDepartment of Urology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo 409-3898, JapanDivision of Molecular Signaling, Department of the Advanced Biomedical Research, Interdisciplinary Graduate School of Medicine, University of Yamanashi, Chuo 409-3898, JapanTanshinone IIA (Tan IIA), an active ingredient of Danshen, is a well-used drug to treat cardiovascular diseases. Currently, the mechanisms involved remain poorly understood. Given that many actions of Tan IIA could be similarly achieved by hydrogen sulfide (H<sub>2</sub>S), we speculated that Tan IIA might work through the induction of endogenous H<sub>2</sub>S. This study was to test this hypothesis. Exposure to endothelial cells to Tan IIA elevated H<sub>2</sub>S-synthesizing enzyme cystathionine γ-Lyase (CSE), associated with an increased level of endogenous H<sub>2</sub>S and free thiol activity. Further analysis revealed that this effect of Tan IIA was mediated by an estrogen receptor (ER) and cAMP signaling pathway. It stimulated VASP and CREB phosphorylation. Inhibition of ER or PKA abolished the CSE-elevating effect, whereas activation of ER or PKA mimicked the effect of Tan IIA. In an oxidative endothelial cell injury model, Tan IIA potently attenuated oxidative stress and inhibited cell death. In support of a role of endogenous H<sub>2</sub>S, inhibition of CSE aggerated oxidative cell injury. On the contrary, supplement of H<sub>2</sub>S attenuated cell injury. Collectively, our study characterized endogenous H<sub>2</sub>S as a novel mediator underlying the pharmacological actions of Tan IIA. Given the multifaceted functions of H<sub>2</sub>S, the H<sub>2</sub>S-stimulating property of Tan IIA could be exploited for treating many diseases.https://www.mdpi.com/2076-3921/10/7/1007tanshinone IIAcystathionine γ-lyaseoxidative cell injuryhydrogen sulfideprotein kinase Aendothelial cells |
| spellingShingle | Qiaojing Yan Zhimin Mao Jingru Hong Kun Gao Manabu Niimi Takahiko Mitsui Jian Yao Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury Antioxidants tanshinone IIA cystathionine γ-lyase oxidative cell injury hydrogen sulfide protein kinase A endothelial cells |
| title | Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury |
| title_full | Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury |
| title_fullStr | Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury |
| title_full_unstemmed | Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury |
| title_short | Tanshinone IIA Stimulates Cystathionine γ-Lyase Expression and Protects Endothelial Cells from Oxidative Injury |
| title_sort | tanshinone iia stimulates cystathionine γ lyase expression and protects endothelial cells from oxidative injury |
| topic | tanshinone IIA cystathionine γ-lyase oxidative cell injury hydrogen sulfide protein kinase A endothelial cells |
| url | https://www.mdpi.com/2076-3921/10/7/1007 |
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