Cargando…
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...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469382/ https://www.ncbi.nlm.nih.gov/pubmed/34573059 http://dx.doi.org/10.3390/antiox10091427 |
_version_ | 1784573916795109376 |
---|---|
author | Merk, Dennis Ptok, Johannes Jakobs, Philipp von Ameln, Florian Greulich, Jan Kluge, Pia Semperowitsch, Kathrin Eckermann, Olaf Schaal, Heiner Ale-Agha, Niloofar Altschmied, Joachim Haendeler, Judith |
author_facet | Merk, Dennis Ptok, Johannes Jakobs, Philipp von Ameln, Florian Greulich, Jan Kluge, Pia Semperowitsch, Kathrin Eckermann, Olaf Schaal, Heiner Ale-Agha, Niloofar Altschmied, Joachim Haendeler, Judith |
author_sort | Merk, Dennis |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-8469382 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-84693822021-09-27 Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and Apoptosis Merk, Dennis Ptok, Johannes Jakobs, Philipp von Ameln, Florian Greulich, Jan Kluge, Pia Semperowitsch, Kathrin Eckermann, Olaf Schaal, Heiner Ale-Agha, Niloofar Altschmied, Joachim Haendeler, Judith Antioxidants (Basel) Article 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. MDPI 2021-09-07 /pmc/articles/PMC8469382/ /pubmed/34573059 http://dx.doi.org/10.3390/antiox10091427 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Merk, Dennis Ptok, Johannes Jakobs, Philipp von Ameln, Florian Greulich, Jan Kluge, Pia Semperowitsch, Kathrin Eckermann, Olaf Schaal, Heiner Ale-Agha, Niloofar Altschmied, Joachim Haendeler, Judith Selenoprotein T Protects Endothelial Cells against Lipopolysaccharide-Induced Activation and 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 | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469382/ https://www.ncbi.nlm.nih.gov/pubmed/34573059 http://dx.doi.org/10.3390/antiox10091427 |
work_keys_str_mv | AT merkdennis selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT ptokjohannes selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT jakobsphilipp selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT vonamelnflorian selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT greulichjan selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT klugepia selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT semperowitschkathrin selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT eckermannolaf selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT schaalheiner selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT aleaghaniloofar selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT altschmiedjoachim selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis AT haendelerjudith selenoproteintprotectsendothelialcellsagainstlipopolysaccharideinducedactivationandapoptosis |