ROS in diabetic atria regulate SK2 degradation by Atrogin-1 through the NF-κB signaling pathway.

Autor: Xu J; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China; Senior Department of Cardiology, The Sixth Medical Center of PLA General Hospital, Beijing, China., Zhang D; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Ma Y; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Du H; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Wang Y; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China., Luo W; Institute of Cardiovascular and Vascular Disease, Shaanxi University of Traditional Chinese Medicine, Xianyang, China., Wang R; Department of Cardiology, Wuxi People's Hospital Affiliated to Nanjing Medical University, Wuxi, Jiangsu, China., Yi F; Department of Cardiovascular Diseases, Xijing Hospital, Fourth Military Medical University, Xi'an, China. Electronic address: yi12fu56@126.com.
Jazyk: angličtina
Zdroj: The Journal of biological chemistry [J Biol Chem] 2024 Mar; Vol. 300 (3), pp. 105735. Date of Electronic Publication: 2024 Feb 08.
DOI: 10.1016/j.jbc.2024.105735
Abstrakt: One of the independent risk factors for atrial fibrillation is diabetes mellitus (DM); however, the underlying mechanisms causing atrial fibrillation in DM are unknown. The underlying mechanism of Atrogin-1-mediated SK2 degradation and associated signaling pathways are unclear. The aim of this study was to elucidate the relationship among reactive oxygen species (ROS), the NF-κB signaling pathway, and Atrogin-1 protein expression in the atrial myocardia of DM mice. We found that SK2 expression was downregulated comitant with increased ROS generation and enhanced NF-κB signaling activation in the atrial cardiomyocytes of DM mice. These observations were mimicked by exogenously applicating H 2 O 2 and by high glucose culture conditions in HL-1 cells. Inhibition of ROS production by diphenyleneiodonium chloride or silencing of NF-κB by siRNA decreased the protein expression of NF-κB and Atrogin-1 and increased that of SK2 in HL-1 cells with high glucose culture. Moreover, chromatin immunoprecipitation assay demonstrated that NF-κB/p65 directly binds to the promoter of the FBXO32 gene (encoding Atrogin-1), regulating the FBXO32 transcription. Finally, we evaluated the therapeutic effects of curcumin, known as a NF-κB inhibitor, on Atrogin-1 and SK2 expression in DM mice and confirmed that oral administration of curcumin for 4 weeks significantly suppressed Atrogin-1 expression and protected SK2 expression against hyperglycemia. In summary, the results from this study indicated that the ROS/NF-κB signaling pathway participates in Atrogin-1-mediated SK2 regulation in the atria of streptozotocin-induced DM mice.
Competing Interests: Conflict of interest The authors declare that they have no no conflicts of interest with the contents of this article.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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