دورية أكاديمية
Specific O-GlcNAc modification at Ser-615 modulates eNOS function
| العنوان: | Specific O-GlcNAc modification at Ser-615 modulates eNOS function |
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| المؤلفون: | Kulwant S. Aulak, Jarrod W. Barnes, Liping Tian, Noel E. Mellor, Mohammad M. Haque, Belinda Willard, Ling Li, Suzy C. Comhair, Dennis J. Stuehr, Raed A. Dweik |
| المصدر: | Redox Biology, Vol 36, Iss , Pp 101625- (2020) |
| بيانات النشر: | Elsevier, 2020. |
| سنة النشر: | 2020 |
| المجموعة: | LCC:Medicine (General) LCC:Biology (General) |
| مصطلحات موضوعية: | Endothelial nitric oxide synthetase, O-GlcNAc modification, Pulmonary arterial hypertension, Nitric oxide, Medicine (General), R5-920, Biology (General), QH301-705.5 |
| الوصف: | Idiopathic pulmonary arterial hypertension (IPAH) is a progressive and devastating disease characterized by vascular smooth muscle and endothelial cell proliferation leading to a narrowing of the vessels in the lung. The increased resistance in the lung and the higher pressures generated result in right heart failure. Nitric Oxide (NO) deficiency is considered a hallmark of IPAH and altered function of endothelial nitric oxide synthase (eNOS), decreases NO production. We recently demonstrated that glucose dysregulation results in augmented protein serine/threonine hydroxyl-linked N-Acetyl-glucosamine (O-GlcNAc) modification in IPAH. In diabetes, dysregulated glucose metabolism has been shown to regulate eNOS function through inhibition of Ser-1177 phosphorylation. However, the link between O-GlcNAc and eNOS function remains unknown. Here we show that increased protein O-GlcNAc occurs on eNOS in PAH and Ser-615 appears to be a novel site of O-GlcNAc modification resulting in reduced eNOS dimerization. Functional characterization of Ser-615 demonstrated the importance of this residue on the regulation of eNOS activity through control of Ser-1177 phosphorylation. Here we demonstrate a previously unidentified regulatory mechanism of eNOS whereby the O-GlcNAc modification of Ser-615 results in reduced eNOS activity and endothelial dysfunction under conditions of glucose dysregulation. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2213-2317 |
| العلاقة: | http://www.sciencedirect.com/science/article/pii/S2213231720308302Test; https://doaj.org/toc/2213-2317Test |
| DOI: | 10.1016/j.redox.2020.101625 |
| الوصول الحر: | https://doaj.org/article/cb1104b7473e429ea36d8a6d877a814eTest |
| رقم الانضمام: | edsdoj.b1104b7473e429ea36d8a6d877a814e |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 22132317 |
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| DOI: | 10.1016/j.redox.2020.101625 |