UGCG modulates heart hypertrophy through B4GalT5-mediated mitochondrial oxidative stress and the ERK signaling pathway

Cellular & Molecular Biology Letters

Research

Bing Wu¹  Zhao Fang¹  Haoliang Wu¹  Bo Tao¹  Shengyu Cui¹  Jixian Gao¹  Xutao Zhang¹  Hao Xia¹  Shan Hu¹  Ming Li¹  Lin Xu²  Yuhua Li³ 

[1] Department of Cardiology, Renmin Hospital of Wuhan University, 430060, Wuhan, China;Cardiovascular Research Institute, Wuhan University, 430060, Wuhan, China;Hubei Key Laboratory of Cardiology, 430060, Wuhan, China;Department of Geriatrics, Renmin Hospital of Wuhan University, 430060, Wuhan, Hubei, China;Intensive Care Unit, Wuhan Children’s Hospital (Wuhan Maternal and Child Healthcare Hospital), Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China;

关键词: Heart hypertrophy;    UGCG;    B4GalT5;    ERK signaling;   

DOI  :  10.1186/s11658-023-00484-3

 received in 2023-04-27, accepted in 2023-08-17,  发布年份 2023

来源: Springer

【 摘 要 】

Mechanical pressure overload and other stimuli often contribute to heart hypertrophy, a significant factor in the induction of heart failure. The UDP-glucose ceramide glycosyltransferase (UGCG) enzyme plays a crucial role in the metabolism of sphingolipids through the production of glucosylceramide. However, its role in heart hypertrophy remains unknown. In this study, UGCG was induced in response to pressure overload in vivo and phenylephrine stimulation in vitro. Additionally, UGCG downregulation ameliorated cardiomyocyte hypertrophy, improved cardiomyocyte mitochondrial oxidative stress, and reduced the ERK signaling pathway. Conversely, UGCG overexpression in cardiomyocytes promoted heart hypertrophy development, aggravated mitochondrial oxidative stress, and stimulated ERK signaling. Furthermore, the interaction between beta-1,4-galactosyltransferase 5 (B4GalT5), which catalyses the synthesis of lactosylceramide, and UGCG was identified, which also functions as a synergistic molecule of UGCG. Notably, limiting the expression of B4GalT5 impaired the capacity of UGCG to promote myocardial hypertrophy, suggesting that B4GalT5 acts as an intermediary for UGCG. Overall, this study highlights the potential of UGCG as a modulator of heart hypertrophy, rendering it a potential target for combating heart hypertrophy.

【 授权许可】

CC BY   
© University of Wroclav 2023

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