Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation
Cystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid s...
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Format: | Article |
Language: | English |
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Elsevier
2020-01-01
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Series: | Redox Biology |
Online Access: | http://www.sciencedirect.com/science/article/pii/S2213231719312261 |
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record_format |
Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sofia-Iris Bibli Jiong Hu Matthias S. Leisegang Janina Wittig Sven Zukunft Andrea Kapasakalidi Beate Fisslthaler Diamantis Tsilimigras Georgios Zografos Konstantinos Filis Ralf P. Brandes Andreas Papapetropoulos Fragiska Sigala Ingrid Fleming |
spellingShingle |
Sofia-Iris Bibli Jiong Hu Matthias S. Leisegang Janina Wittig Sven Zukunft Andrea Kapasakalidi Beate Fisslthaler Diamantis Tsilimigras Georgios Zografos Konstantinos Filis Ralf P. Brandes Andreas Papapetropoulos Fragiska Sigala Ingrid Fleming Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation Redox Biology |
author_facet |
Sofia-Iris Bibli Jiong Hu Matthias S. Leisegang Janina Wittig Sven Zukunft Andrea Kapasakalidi Beate Fisslthaler Diamantis Tsilimigras Georgios Zografos Konstantinos Filis Ralf P. Brandes Andreas Papapetropoulos Fragiska Sigala Ingrid Fleming |
author_sort |
Sofia-Iris Bibli |
title |
Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
title_short |
Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
title_full |
Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
title_fullStr |
Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
title_full_unstemmed |
Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
title_sort |
shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation |
publisher |
Elsevier |
series |
Redox Biology |
issn |
2213-2317 |
publishDate |
2020-01-01 |
description |
Cystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid shear stress/flow. Fluid shear stress decreased CSE expression in human and murine endothelial cells and was negatively correlated with the transcription factor Krüppel-like factor (KLF) 2. CSE was identified as a direct target of the KLF2-regulated microRNA, miR-27b and high expression of CSE in native human plaque-derived endothelial cells, was also inversely correlated with KLF2 and miR-27b levels. One consequence of decreased CSE expression was the loss of Prx6 sulfhydration (on Cys47), which resulted in Prx6 hyperoxidation, decamerization and inhibition, as well as a concomitant increase in endothelial cell reactive oxygen species and lipid membrane peroxidation. H2Sn supplementation in vitro was able to reverse the redox state of Prx6. Statin therapy, which is known to activate KLF2, also decreased CSE expression but increased CSE activity by preventing its phosphorylation on Ser377. As a result, the sulfhydration of Prx6 was partially restored in samples from plaque containing arteries from statin-treated donors. Taken together, the regulation of CSE expression by shear stress/disturbed flow is dependent on KLF2 and miR-27b. Moreover, in murine and human arteries CSE acts to maintain endothelial redox balance at least partly by targeting Prx6 to prevent its decamerization and inhibition of its peroxidase activity. |
url |
http://www.sciencedirect.com/science/article/pii/S2213231719312261 |
work_keys_str_mv |
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doaj-b82f9f2169ae4462a428be0f43fcc28e2020-11-25T01:27:48ZengElsevierRedox Biology2213-23172020-01-0128Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidationSofia-Iris Bibli0Jiong Hu1Matthias S. Leisegang2Janina Wittig3Sven Zukunft4Andrea Kapasakalidi5Beate Fisslthaler6Diamantis Tsilimigras7Georgios Zografos8Konstantinos Filis9Ralf P. Brandes10Andreas Papapetropoulos11Fragiska Sigala12Ingrid Fleming13Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, GermanyInstitute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, GermanyGerman Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany; Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, GermanyInstitute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, GermanyInstitute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, GermanyInstitute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, GermanyGerman Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, GermanyFirst Propedeutic Department of Surgery, Vascular Surgery Division, Hippokration Hospital, National and Kapodistrian University of Athens Medical School, Athens, GreeceFirst Propedeutic Department of Surgery, Vascular Surgery Division, Hippokration Hospital, National and Kapodistrian University of Athens Medical School, Athens, GreeceFirst Propedeutic Department of Surgery, Vascular Surgery Division, Hippokration Hospital, National and Kapodistrian University of Athens Medical School, Athens, GreeceGerman Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany; Institute for Cardiovascular Physiology, Goethe University, Frankfurt am Main, GermanyLaboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens Medical School, Athens, Greece; Clinical, Experimental Surgery and Translational Research Center, Biomedical Research Foundation of the Academy of Athens, Soranou Ephessiou 4, Athens, 11527, GreeceFirst Propedeutic Department of Surgery, Vascular Surgery Division, Hippokration Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece; Corresponding author.Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Frankfurt am Main, Germany; German Center of Cardiovascular Research (DZHK), Partner site RheinMain, Frankfurt am Main, Germany; Corresponding author. Institute for Vascular Signalling, Centre for Molecular Medicine, Goethe University, Theodor Stern Kai 7, 60596, Frankfurt am Main, GermanyCystathionine γ lyase (CSE) is the major source of hydrogen sulfide-derived species (H2Sn) in endothelial cells and plays an important role in protecting against atherosclerosis. Here we investigated the molecular mechanisms underlying the regulation of CSE expression in endothelial cells by fluid shear stress/flow. Fluid shear stress decreased CSE expression in human and murine endothelial cells and was negatively correlated with the transcription factor Krüppel-like factor (KLF) 2. CSE was identified as a direct target of the KLF2-regulated microRNA, miR-27b and high expression of CSE in native human plaque-derived endothelial cells, was also inversely correlated with KLF2 and miR-27b levels. One consequence of decreased CSE expression was the loss of Prx6 sulfhydration (on Cys47), which resulted in Prx6 hyperoxidation, decamerization and inhibition, as well as a concomitant increase in endothelial cell reactive oxygen species and lipid membrane peroxidation. H2Sn supplementation in vitro was able to reverse the redox state of Prx6. Statin therapy, which is known to activate KLF2, also decreased CSE expression but increased CSE activity by preventing its phosphorylation on Ser377. As a result, the sulfhydration of Prx6 was partially restored in samples from plaque containing arteries from statin-treated donors. Taken together, the regulation of CSE expression by shear stress/disturbed flow is dependent on KLF2 and miR-27b. Moreover, in murine and human arteries CSE acts to maintain endothelial redox balance at least partly by targeting Prx6 to prevent its decamerization and inhibition of its peroxidase activity.http://www.sciencedirect.com/science/article/pii/S2213231719312261 |