Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice

• Published in: International journal of biological sciences 2022, Vol.18 (2), p.826-840
• Main Authors: Guo, Zhen, Tuo, Hu, Tang, Nan, Liu, Fang-Yuan, Ma, Shu-Qing, An, Peng, Yang, Dan, Wang, Min-Yu, Fan, Di, Yang, Zheng, Tang, Qi-Zhu
• Format: Article
• Language: English
• Subjects: Antibodies; Apoptosis; Cardiac muscle; Cardiomyocytes; Cardiomyopathy; Cardiovascular disease; Catabolism; Catheters; Cell death; Diabetes; Diabetes mellitus; ErbB-2 protein; Ethanol; Exo-a-sialidase; Fibrosis; Glucose; Growth factors; Heart; In vivo methods and tests; Inflammation; Insulin; Laboratory animals; LKB1 protein; Lysosomal protein; Membranes; Myocardium; Myocytes; Neonates; Oxidative stress; Proteins; Reactive oxygen species; Research Paper; Signal transduction; Streptozocin; Ventricle
• ISSN: 1449-2288; 1449-2288
• DOI: 10.7150/ijbs.65938

Diabetic cardiomyopathy (DCM) is associated with oxidative stress and augmented inflammation in the heart. Neuraminidases (NEU) 1 has initially been described as a lysosomal protein which plays a role in the catabolism of glycosylated proteins. We investigated the role of NEU1 in the myocardium in diabetic heart. Streptozotocin (STZ) was injected intraperitoneally to induce diabetes in mice. Neonatal rat ventricular myocytes (NRVMs) were used to verify the effect of shNEU1 . NEU1 is up-regulated in cardiomyocytes under diabetic conditions. NEU1 inhibition alleviated oxidative stress, inflammation and apoptosis, and improved cardiac function in STZ-induced diabetic mice. Furthermore, NEU1 inhibition also attenuated the high glucose-induced increased reactive oxygen species generation, inflammation and, cell death . ShNEU1 activated Sirtuin 3 (SIRT3) signaling pathway, and SIRT3 deficiency blocked shNEU1-mediated cardioprotective effects . More importantly, we found AMPKα was responsible for the elevation of SIRT3 expression via AMPKα-deficiency studies and . Knockdown of LKB1 reversed the effect elicited by shNEU1 . In conclusion, NEU1 inhibition activates AMPKα via LKB1, and subsequently activates sirt3, thereby regulating fibrosis, inflammation, apoptosis and oxidative stress in diabetic myocardial tissue.