TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide
Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H<sub>2</sub>S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/3/734 |
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| author | Lorena Diaz Sanchez Lissette Sanchez-Aranguren Keqing Wang Corinne M. Spickett Helen R. Griffiths Irundika H. K. Dias |
| author_facet | Lorena Diaz Sanchez Lissette Sanchez-Aranguren Keqing Wang Corinne M. Spickett Helen R. Griffiths Irundika H. K. Dias |
| author_sort | Lorena Diaz Sanchez |
| collection | DOAJ |
| description | Endothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H<sub>2</sub>S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H<sub>2</sub>S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H<sub>2</sub>S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H<sub>2</sub>S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H<sub>2</sub>S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H<sub>2</sub>S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H<sub>2</sub>S via the mitochondrial-driven pathway. |
| first_indexed | 2024-03-11T07:00:51Z |
| format | Article |
| id | doaj.art-bda30a1bb8a4488387ec7c9c7d4ea7f2 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T07:00:51Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-bda30a1bb8a4488387ec7c9c7d4ea7f22023-11-17T09:19:01ZengMDPI AGAntioxidants2076-39212023-03-0112373410.3390/antiox12030734TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen SulfideLorena Diaz Sanchez0Lissette Sanchez-Aranguren1Keqing Wang2Corinne M. Spickett3Helen R. Griffiths4Irundika H. K. Dias5Aston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UKAston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UKAston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UKSchool of Biosciences, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UKSwansea Medical School, Swansea University, Singleton Park, Swansea SA2 8PP, UKAston Medical School, College of Health and Life Sciences, Aston University, Aston Triangle, Birmingham B4 7ET, UKEndothelial dysfunction is implicated in the development and aggravation of cardiovascular complications. Among the endothelium-released vasoactive factors, hydrogen sulfide (H<sub>2</sub>S) has been investigated for its beneficial effects on the vasculature through anti-inflammatory and redox-modulating regulatory mechanisms. Reduced H<sub>2</sub>S bioavailability is reported in chronic diseases such as cardiovascular disease, diabetes, atherosclerosis and preeclampsia, suggesting the value of investigating mechanisms, by which H<sub>2</sub>S acts as a vasoprotective gasotransmitter. We explored whether the protective effects of H<sub>2</sub>S were linked to the mitochondrial health of endothelial cells and the mechanisms by which H<sub>2</sub>S rescues apoptosis. Here, we demonstrate that endothelial dysfunction induced by TNF-α increased endothelial oxidative stress and induced apoptosis via mitochondrial cytochrome c release and caspase activation over 24 h. TNF-α also affected mitochondrial morphology and altered the mitochondrial network. Post-treatment with the slow-releasing H<sub>2</sub>S donor, GYY4137, alleviated oxidising redox state, decreased pro-caspase 3 activity, and prevented endothelial apoptosis caused by TNF-α alone. In addition, exogenous GYY4137 enhanced S-sulfhydration of pro-caspase 3 and improved mitochondrial health in TNF-α exposed cells. These data provide new insights into molecular mechanisms for cytoprotective effects of H<sub>2</sub>S via the mitochondrial-driven pathway.https://www.mdpi.com/2076-3921/12/3/734vascular dysfunctionhydrogen sulfideoxidative stressinflammationmitochondrial function |
| spellingShingle | Lorena Diaz Sanchez Lissette Sanchez-Aranguren Keqing Wang Corinne M. Spickett Helen R. Griffiths Irundika H. K. Dias TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide Antioxidants vascular dysfunction hydrogen sulfide oxidative stress inflammation mitochondrial function |
| title | TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide |
| title_full | TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide |
| title_fullStr | TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide |
| title_full_unstemmed | TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide |
| title_short | TNF-α-Mediated Endothelial Cell Apoptosis Is Rescued by Hydrogen Sulfide |
| title_sort | tnf α mediated endothelial cell apoptosis is rescued by hydrogen sulfide |
| topic | vascular dysfunction hydrogen sulfide oxidative stress inflammation mitochondrial function |
| url | https://www.mdpi.com/2076-3921/12/3/734 |
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