Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis
Sepsis is an exaggerated immune response upon infection with lipopolysaccharide (LPS) as the main causative agent. LPS-induced activation and apoptosis of endothelial cells (EC) can lead to organ dysfunction and finally organ failure. We previously demonstrated that the first twenty amino acids of t...
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MDPI AG
2021-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/9/1427 |
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| author | Dennis Merk Johannes Ptok Philipp Jakobs Florian von Ameln Jan Greulich Pia Kluge Kathrin Semperowitsch Olaf Eckermann Heiner Schaal Niloofar Ale-Agha Joachim Altschmied Judith Haendeler |
| author_facet | Dennis Merk Johannes Ptok Philipp Jakobs Florian von Ameln Jan Greulich Pia Kluge Kathrin Semperowitsch Olaf Eckermann Heiner Schaal Niloofar Ale-Agha Joachim Altschmied Judith Haendeler |
| author_sort | Dennis Merk |
| collection | DOAJ |
| description | Sepsis is an exaggerated immune response upon infection with lipopolysaccharide (LPS) as the main causative agent. LPS-induced activation and apoptosis of endothelial cells (EC) can lead to organ dysfunction and finally organ failure. We previously demonstrated that the first twenty amino acids of the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) are sufficient to inhibit EC apoptosis. To identify genes whose regulation by LPS is affected by this N-terminal APEX1 peptide, EC were transduced with an expression vector for the APEX1 peptide or an empty control vector and treated with LPS. Following RNA deep sequencing, genes upregulated in LPS-treated EC expressing the APEX1 peptide were identified bioinformatically. Selected candidates were validated by semi-quantitative real time PCR, a promising one was Selenoprotein T (SELENOT). For functional analyses, an expression vector for SELENOT was generated. To study the effect of SELENOT expression on LPS-induced EC activation and apoptosis, the SELENOT vector was transfected in EC. Immunostaining showed that SELENOT was expressed and localized in the ER. EC transfected with the SELENOT plasmid showed no activation and reduced apoptosis induced by LPS. SELENOT as well as APEX1(1-20) can protect EC against activation and apoptosis and could provide new therapeutic approaches in the treatment of sepsis. |
| first_indexed | 2024-03-10T07:57:22Z |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T07:57:22Z |
| publishDate | 2021-09-01 |
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| series | Antioxidants |
| spelling | doaj.art-ad537b1b030145a1a01499ff88b435512023-11-22T11:48:35ZengMDPI AGAntioxidants2076-39212021-09-01109142710.3390/antiox10091427Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and ApoptosisDennis Merk0Johannes Ptok1Philipp Jakobs2Florian von Ameln3Jan Greulich4Pia Kluge5Kathrin Semperowitsch6Olaf Eckermann7Heiner Schaal8Niloofar Ale-Agha9Joachim Altschmied10Judith Haendeler11Environmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute for Virology, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, Germany and IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, Germany and IUF-Leibniz Research Institute for Environmental Medicine, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyInstitute for Virology, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanyEnvironmentally-Induced Cardiovascular Degeneration, Clinical Chemistry and Laboratory Diagnostics, Medical Faculty, University Hospital and Heinrich-Heine University Düsseldorf, 40225 Düsseldorf, GermanySepsis is an exaggerated immune response upon infection with lipopolysaccharide (LPS) as the main causative agent. LPS-induced activation and apoptosis of endothelial cells (EC) can lead to organ dysfunction and finally organ failure. We previously demonstrated that the first twenty amino acids of the Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APEX1) are sufficient to inhibit EC apoptosis. To identify genes whose regulation by LPS is affected by this N-terminal APEX1 peptide, EC were transduced with an expression vector for the APEX1 peptide or an empty control vector and treated with LPS. Following RNA deep sequencing, genes upregulated in LPS-treated EC expressing the APEX1 peptide were identified bioinformatically. Selected candidates were validated by semi-quantitative real time PCR, a promising one was Selenoprotein T (SELENOT). For functional analyses, an expression vector for SELENOT was generated. To study the effect of SELENOT expression on LPS-induced EC activation and apoptosis, the SELENOT vector was transfected in EC. Immunostaining showed that SELENOT was expressed and localized in the ER. EC transfected with the SELENOT plasmid showed no activation and reduced apoptosis induced by LPS. SELENOT as well as APEX1(1-20) can protect EC against activation and apoptosis and could provide new therapeutic approaches in the treatment of sepsis.https://www.mdpi.com/2076-3921/10/9/1427APEX1(1-20)Selenoprotein Tlipopolysaccharideendothelial cell activationapoptosis |
| spellingShingle | Dennis Merk Johannes Ptok Philipp Jakobs Florian von Ameln Jan Greulich Pia Kluge Kathrin Semperowitsch Olaf Eckermann Heiner Schaal Niloofar Ale-Agha Joachim Altschmied Judith Haendeler Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis Antioxidants APEX1(1-20) Selenoprotein T lipopolysaccharide endothelial cell activation apoptosis |
| title | Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis |
| title_full | Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis |
| title_fullStr | Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis |
| title_full_unstemmed | Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis |
| title_short | Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis |
| title_sort | selenoprotein t protects endothelial cells against lipopolysaccharide induced activation and apoptosis |
| topic | APEX1(1-20) Selenoprotein T lipopolysaccharide endothelial cell activation apoptosis |
| url | https://www.mdpi.com/2076-3921/10/9/1427 |
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