Unknown

Dataset Information

0

Specific O-GlcNAc modification at Ser-615 modulates eNOS function.


ABSTRACT: 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.

SUBMITTER: Aulak KS 

PROVIDER: S-EPMC7334407 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 th  ...[more]

Similar Datasets

| S-EPMC8163736 | biostudies-literature
| S-EPMC3736601 | biostudies-literature
| S-EPMC2815191 | biostudies-literature
| S-EPMC8191289 | biostudies-literature
| S-EPMC4840301 | biostudies-literature
| S-EPMC5575132 | biostudies-other
| S-EPMC7253032 | biostudies-literature
| S-EPMC2615199 | biostudies-literature
| S-EPMC4401012 | biostudies-literature
| S-EPMC4116059 | biostudies-literature