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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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