Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866
Abstract O-GlcNAcylation, an energy-sensitive posttranslational modification, can regulate the activity of endothelial nitric oxide synthase (eNOS). Previous studies found that Thr866 is the key site for low-glucose-mediated regulation of eNOS O-GlcNAc. However, it is not known whether this activity...
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2021-05-01
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Series: | Scientific Reports |
Online Access: | https://doi.org/10.1038/s41598-021-90321-4 |
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doaj-43533d2a51c8416b91c95cafcb4730622021-05-30T11:34:18ZengNature Publishing GroupScientific Reports2045-23222021-05-011111910.1038/s41598-021-90321-4Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866Chang Li0An He1Yongzheng Guo2Xiyang Yang3Minghao Luo4Zhe Cheng5Longxiang Huang6Yong Xia7Suxin Luo8Division of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityDivision of Cardiology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract O-GlcNAcylation, an energy-sensitive posttranslational modification, can regulate the activity of endothelial nitric oxide synthase (eNOS). Previous studies found that Thr866 is the key site for low-glucose-mediated regulation of eNOS O-GlcNAc. However, it is not known whether this activity functions through the Thr866 site concomitant with other physical and chemical factors. Therefore, we first explored the effects of physical and chemical factors on eNOS O-GlcNAc and its Thr866 site. In this study, hypertonic stress, hyperthermia and hydrogen peroxide all increased the expression levels of eNOS O-GlcNAc, whereas hypoxia and high levels of alcohol had no effect. on the expression levels of eNOS O-GlcNAc; by contrast, low pH led to a decrease in eNOS O-GlcNAc levels. Notably, eNOS O-GlcNAc protein levels were unchanged after Thr866 site mutation only under hypertonic conditions, suggesting that hypertonic stress may act through the Thr866 site. Upon exploring the mechanism of hypertonic stress on eNOS O-GlcNAc activity and function, we found that hypertonic stress can upregulate the expression of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which is dependent on AMPK. When AMPK was knocked out, the upregulation of OGT expression and increased O-GlcNAc modifications induced by hypertonic stress were reversed.https://doi.org/10.1038/s41598-021-90321-4 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Chang Li An He Yongzheng Guo Xiyang Yang Minghao Luo Zhe Cheng Longxiang Huang Yong Xia Suxin Luo |
spellingShingle |
Chang Li An He Yongzheng Guo Xiyang Yang Minghao Luo Zhe Cheng Longxiang Huang Yong Xia Suxin Luo Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 Scientific Reports |
author_facet |
Chang Li An He Yongzheng Guo Xiyang Yang Minghao Luo Zhe Cheng Longxiang Huang Yong Xia Suxin Luo |
author_sort |
Chang Li |
title |
Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 |
title_short |
Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 |
title_full |
Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 |
title_fullStr |
Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 |
title_full_unstemmed |
Hypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-866 |
title_sort |
hypertonic stress modulates enos function through o-glcnac modification at thr-866 |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2021-05-01 |
description |
Abstract O-GlcNAcylation, an energy-sensitive posttranslational modification, can regulate the activity of endothelial nitric oxide synthase (eNOS). Previous studies found that Thr866 is the key site for low-glucose-mediated regulation of eNOS O-GlcNAc. However, it is not known whether this activity functions through the Thr866 site concomitant with other physical and chemical factors. Therefore, we first explored the effects of physical and chemical factors on eNOS O-GlcNAc and its Thr866 site. In this study, hypertonic stress, hyperthermia and hydrogen peroxide all increased the expression levels of eNOS O-GlcNAc, whereas hypoxia and high levels of alcohol had no effect. on the expression levels of eNOS O-GlcNAc; by contrast, low pH led to a decrease in eNOS O-GlcNAc levels. Notably, eNOS O-GlcNAc protein levels were unchanged after Thr866 site mutation only under hypertonic conditions, suggesting that hypertonic stress may act through the Thr866 site. Upon exploring the mechanism of hypertonic stress on eNOS O-GlcNAc activity and function, we found that hypertonic stress can upregulate the expression of O-linked N-acetylglucosamine (GlcNAc) transferase (OGT), which is dependent on AMPK. When AMPK was knocked out, the upregulation of OGT expression and increased O-GlcNAc modifications induced by hypertonic stress were reversed. |
url |
https://doi.org/10.1038/s41598-021-90321-4 |
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