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

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

doi:10.7150/ijbs.65938

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Int J Biol Sci 2022; 18(2):826-840. doi:10.7150/ijbs.65938 This issue Cite

Research Paper

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

Zhen Guo^1,2*, Hu Tuo^1,2*, Nan Tang^3,4*, Fang-Yuan Liu^1,2*, Shu-Qing Ma^1,2, Peng An^1,2, Dan Yang^1,2, Min-Yu Wang^1,2, Di Fan^1,2✉, Zheng Yang^1,2✉, Qi-Zhu Tang^1,2✉

1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, RP China
2. Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan, RP China
3. The Affiliated Suqian Hospital of Xuzhou Medical University, Suqian 223800, RP China
4. People's Hospital affiliated to Nanjing Drama Tower Hospital Group, Suqian 223800, RP China
Z.G, H.T, N.T, and FY.L contributed equally.
*These authors contributed equally to this work.

✉ Corresponding authors: Di Fan, Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute, Hubei Key Laboratory of Metabolic and Chronic Diseases, Wuhan University at Jiefang Road 238, Wuhan 430060, RP China. Te More

Citation:

Guo Z, Tuo H, Tang N, Liu FY, Ma SQ, An P, Yang D, Wang MY, Fan D, Yang Z, Tang QZ. Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. Int J Biol Sci 2022; 18(2):826-840. doi:10.7150/ijbs.65938. https://www.ijbs.com/v18p0826.htm

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Abstract

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 in vitro. 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 in vitro. ShNEU1 activated Sirtuin 3 (SIRT3) signaling pathway, and SIRT3 deficiency blocked shNEU1-mediated cardioprotective effects in vitro. More importantly, we found AMPKα was responsible for the elevation of SIRT3 expression via AMPKα-deficiency studies in vitro and in vivo. Knockdown of LKB1 reversed the effect elicited by shNEU1 in vitro. In conclusion, NEU1 inhibition activates AMPKα via LKB1, and subsequently activates sirt3, thereby regulating fibrosis, inflammation, apoptosis and oxidative stress in diabetic myocardial tissue.

Keywords: Neuraminidase 1, Diabetic cardiomyopathy, SIRT3, LKB1, AMPKα

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APA

Guo, Z., Tuo, H., Tang, N., Liu, F.Y., Ma, S.Q., An, P., Yang, D., Wang, M.Y., Fan, D., Yang, Z., Tang, Q.Z. (2022). Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. International Journal of Biological Sciences, 18(2), 826-840. https://doi.org/10.7150/ijbs.65938.

ACS

Guo, Z.; Tuo, H.; Tang, N.; Liu, F.Y.; Ma, S.Q.; An, P.; Yang, D.; Wang, M.Y.; Fan, D.; Yang, Z.; Tang, Q.Z. Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. Int. J. Biol. Sci. 2022, 18 (2), 826-840. DOI: 10.7150/ijbs.65938.

NLM

CSE

Guo Z, Tuo H, Tang N, Liu FY, Ma SQ, An P, Yang D, Wang MY, Fan D, Yang Z, Tang QZ. 2022. Neuraminidase 1 deficiency attenuates cardiac dysfunction, oxidative stress, fibrosis, inflammatory via AMPK-SIRT3 pathway in diabetic cardiomyopathy mice. Int J Biol Sci. 18(2):826-840.

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