Hyper-O-GlcNAcylation impairs insulin response against reperfusion-induced myocardial injury and arrhythmias in obesity
Autor: | Caiyao Li, Xinghua Qin, Binghua Liu, Tiannan Jiang, Qiangsun Zheng, Feng Gao, Lingyan Jin |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Male medicine.medical_specialty Cardiotonic Agents Glycosylation medicine.medical_treatment Norleucine Diazooxonorleucine Biophysics Myocardial Reperfusion Injury medicine.disease_cause Biochemistry Acetylglucosamine Cell Line 03 medical and health sciences chemistry.chemical_compound Mice 0302 clinical medicine Glucosamine Internal medicine medicine Animals Humans Insulin Myocardial infarction Obesity Molecular Biology Cardioprotection business.industry Myocardium Arrhythmias Cardiac Cell Biology medicine.disease Cell Hypoxia Mice Mutant Strains Rats Mice Inbred C57BL Disease Models Animal 030104 developmental biology Endocrinology chemistry 030220 oncology & carcinogenesis Biomarker (medicine) business Reperfusion injury Protein Processing Post-Translational Oxidative stress |
Zdroj: | Biochemical and biophysical research communications. 558 |
ISSN: | 1090-2104 |
Popis: | Myocardial ischemia/reperfusion (I/R) injury is a major determinant of morbidity and mortality in patients undergoing treatment for cardiac disease. A variety of treatments are reported to have benefits against reperfusion injury, yet their cardioprotective effects seem to be diminished in obesity, and the underlying mechanism remains elusive. In this study, we found that db/db mice exhibit cardiac hyper-O-GlcNAcylation. In parallel, palmitate treatment (200 mM; 12 h) in H9c2 cells showed an increase in global protein O-GlcNAcylation, along with an impaired insulin response against reperfusion injury. To investigate whether O-GlcNAcylation underlies this phenomenon, glucosamine was used to increase global protein O-GlcNAc levels. Interestingly, histological staining, electrophysiological studies, serum cardiac markers and oxidative stress biomarker assays showed that preischemic treatment with glucosamine attenuated insulin cardioprotection against myocardial infarction, arrhythmia and oxidative stress. Mechanistically, glucosamine treatment decreased insulin-stimulated Akt phosphorylation, a key modulator of cell survival. Furthermore, inhibition of O-GlcNAcylation via 6-diazo-5-oxo- l -norleucine (DON) apparently increased insulin-induced Akt phosphorylation and restored its cardioprotective response against reperfusion injury in palmitate-induced insulin-resistant H9c2 cells. Our findings demonstrated that obesity-induced hyper-O-GlcNAcylation might contribute to the attenuation of insulin cardioprotection against I/R injury. |
Databáze: | OpenAIRE |
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