Role of O-Linked N-Acetyl Glucosamine Posttranslational Modification in Intermittent Hypoxia-induced Cardiac Remodeling
JOURNAL OF CARDIAC FAILURE(2014)
摘要
Intermittent hypoxia, a major phenomenon in the sleep apnea syndrome (SAS), is relevant to cardiovascular events, especially in patients with diabetes mellitus (DM). The aim of this study was to evaluate the role of O-Linked N-Acetyl Glucosamine (O-GlcNAc) posttranslational modification in cardiomyocytes exposed to intermittent hypoxia, using DM and O-N-acetylglucosamine transferase transgenic (OGT-Tg) mice. Male db/db, OGT-Tg, and wild type mice were exposed to intermittent hypoxia (IH; 1 minute of 5% oxygen followed by 5 minutes of 21% oxygen) for 14 days. HEK (Human Embryonic Kidney) 293 cells were kept under sustained hypoxia (3-4 %) for 4, 24, 48 hours. Heart was excised and O-GlcNAc modified proteins, OGT, microtubule-associated protein 1 light chain 3 (LC3) were detected by Western blotting. Although fibroblast proliferation in HEK cells under hypoxia was suppressed by O-GlcNAc, IH increased myocardial degeneration and interstitial fibrosis in DM mice, associated with significant increase of O-GlcNAc modified proteins. On the other hand, the LC3-II/LC3-I ratio was significantly increased by IH in OGT-Tg mice, and cardiomyocyte hypertrophy, mitochondrial destruction, and autophagosomes were observed. IH significantly increased oxidative stress and histological degeneration, especially in DM mice with increased O-GlcNAcylation. On the contrary, OGT-Tg mice showed acceleration of autophagy and IH-induced cardiac remodeling. Thus, O-GlcNAc might play a crucial role in cardiac remodeling caused by intermittent hypoxia.
更多查看译文
关键词
cardiac remodeling,o-linked,n-acetyl,hypoxia-induced
AI 理解论文
溯源树
样例
![](https://originalfileserver.aminer.cn/sys/aminer/pubs/mrt_preview.jpeg)
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要