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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Autores principales: Chang Li, An He, Yongzheng Guo, Xiyang Yang, Minghao Luo, Zhe Cheng, Longxiang Huang, Yong Xia, Suxin Luo
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:43533d2a51c8416b91c95cafcb4730622021-12-02T14:49:10ZHypertonic stress modulates eNOS function through O-GlcNAc modification at Thr-86610.1038/s41598-021-90321-42045-2322https://doaj.org/article/43533d2a51c8416b91c95cafcb4730622021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-90321-4https://doaj.org/toc/2045-2322Abstract 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.Chang LiAn HeYongzheng GuoXiyang YangMinghao LuoZhe ChengLongxiang HuangYong XiaSuxin LuoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
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.
format article
author Chang Li
An He
Yongzheng Guo
Xiyang Yang
Minghao Luo
Zhe Cheng
Longxiang Huang
Yong Xia
Suxin Luo
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 Portfolio
publishDate 2021
url https://doaj.org/article/43533d2a51c8416b91c95cafcb473062
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