Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1
The maintenance of Thioredoxin-1 (Trx-1) levels, and thus of cellular redox homeostasis, is vital for endothelial cells (ECs) to prevent senescence induction. One hallmark of EC functionality, their migratory capacity, which depends on intact mitochondria, is reduced in senescence. Caffeine improves...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/6/1244 |
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| author | Dennis Merk Jan Greulich Annika Vierkant Fiona Cox Olaf Eckermann Florian von Ameln Nadine Dyballa-Rukes Joachim Altschmied Niloofar Ale-Agha Philipp Jakobs Judith Haendeler |
| author_facet | Dennis Merk Jan Greulich Annika Vierkant Fiona Cox Olaf Eckermann Florian von Ameln Nadine Dyballa-Rukes Joachim Altschmied Niloofar Ale-Agha Philipp Jakobs Judith Haendeler |
| author_sort | Dennis Merk |
| collection | DOAJ |
| description | The maintenance of Thioredoxin-1 (Trx-1) levels, and thus of cellular redox homeostasis, is vital for endothelial cells (ECs) to prevent senescence induction. One hallmark of EC functionality, their migratory capacity, which depends on intact mitochondria, is reduced in senescence. Caffeine improves the migratory capacity and mitochondrial functionality of ECs. However, the impact of caffeine on EC senescence has never been investigated. Moreover, a high-fat diet, which can induce EC senescence, results in approximately 1 ng/mL lipopolysaccharide (LPS) in the blood. Therefore, we investigated if low dose endotoxemia induces EC senescence and concomitantly reduces Trx-1 levels, and if caffeine prevents or even reverses senescence. We show that caffeine precludes H<sub>2</sub>O<sub>2</sub>-triggered senescence induction by maintaining endothelial NO synthase (eNOS) levels and preventing the elevation of p21. Notably, 1 ng/mL LPS also increases p21 levels and reduces eNOS and Trx-1 amounts. These effects are completely blocked by co-treatment with caffeine. This prevention of senescence induction is similarly accomplished by the permanent expression of mitochondrial p27, a downstream effector of caffeine. Most importantly, after senescence induction by LPS, a single bolus of caffeine inhibits the increase in p21. This treatment also blocks Trx-1 degradation, suggesting that the reversion of senescence is intimately associated with a normalized redox balance. |
| first_indexed | 2024-03-11T02:50:02Z |
| format | Article |
| id | doaj.art-b92924c50b2547cd84703aa0bc08e0b4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-11T02:50:02Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-b92924c50b2547cd84703aa0bc08e0b42023-11-18T09:03:28ZengMDPI AGAntioxidants2076-39212023-06-01126124410.3390/antiox12061244Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1Dennis Merk0Jan Greulich1Annika Vierkant2Fiona Cox3Olaf Eckermann4Florian von Ameln5Nadine Dyballa-Rukes6Joachim Altschmied7Niloofar Ale-Agha8Philipp Jakobs9Judith Haendeler10Cardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Altschmied Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Altschmied Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Altschmied Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Altschmied Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyCardiovascular Degeneration, Haendeler Group, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital, Heinrich-Heine University Duesseldorf, 40225 Duesseldorf, GermanyThe maintenance of Thioredoxin-1 (Trx-1) levels, and thus of cellular redox homeostasis, is vital for endothelial cells (ECs) to prevent senescence induction. One hallmark of EC functionality, their migratory capacity, which depends on intact mitochondria, is reduced in senescence. Caffeine improves the migratory capacity and mitochondrial functionality of ECs. However, the impact of caffeine on EC senescence has never been investigated. Moreover, a high-fat diet, which can induce EC senescence, results in approximately 1 ng/mL lipopolysaccharide (LPS) in the blood. Therefore, we investigated if low dose endotoxemia induces EC senescence and concomitantly reduces Trx-1 levels, and if caffeine prevents or even reverses senescence. We show that caffeine precludes H<sub>2</sub>O<sub>2</sub>-triggered senescence induction by maintaining endothelial NO synthase (eNOS) levels and preventing the elevation of p21. Notably, 1 ng/mL LPS also increases p21 levels and reduces eNOS and Trx-1 amounts. These effects are completely blocked by co-treatment with caffeine. This prevention of senescence induction is similarly accomplished by the permanent expression of mitochondrial p27, a downstream effector of caffeine. Most importantly, after senescence induction by LPS, a single bolus of caffeine inhibits the increase in p21. This treatment also blocks Trx-1 degradation, suggesting that the reversion of senescence is intimately associated with a normalized redox balance.https://www.mdpi.com/2076-3921/12/6/1244caffeineendothelial cells (EC)lipopolysaccharidesenescenceThioredoxin-1 |
| spellingShingle | Dennis Merk Jan Greulich Annika Vierkant Fiona Cox Olaf Eckermann Florian von Ameln Nadine Dyballa-Rukes Joachim Altschmied Niloofar Ale-Agha Philipp Jakobs Judith Haendeler Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 Antioxidants caffeine endothelial cells (EC) lipopolysaccharide senescence Thioredoxin-1 |
| title | Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 |
| title_full | Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 |
| title_fullStr | Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 |
| title_full_unstemmed | Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 |
| title_short | Caffeine Inhibits Oxidative Stress- and Low Dose Endotoxemia-Induced Senescence—Role of Thioredoxin-1 |
| title_sort | caffeine inhibits oxidative stress and low dose endotoxemia induced senescence role of thioredoxin 1 |
| topic | caffeine endothelial cells (EC) lipopolysaccharide senescence Thioredoxin-1 |
| url | https://www.mdpi.com/2076-3921/12/6/1244 |
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