Ubiquitin-protein ligase E3a (UBE3A) as a new biomarker of cardiac hypertrophy in cell models

doi:10.1016/j.jfda.2018.08.002

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Title:	Ubiquitin-protein ligase E3a (UBE3A) as a new biomarker of cardiac hypertrophy in cell models
Authors:	Cheng, Kai-Chun Li, Yingxiao Chang, Wei-Ting Zhih-Cherng Chen(陳志成) Cheng, Juei-Tang Tsai, Cheng-Chia
Contributors:	Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med Chi Mei Med Ctr, Dept Med Res Chi Mei Med Ctr, Dept Cardiol Chia Nan Univ Pharm & Sci, Dept Pharm Chang Jung Christian Univ, Grad Inst Med Sci Mackay Med Univ, Mackay Mem Hosp, Dept Surg
Keywords:	Hypertrophic signals Hyperglycemia H9c2 cells Isoproterenol Potassium bromate
Date:	2019-01
Issue Date:	2020-07-29 13:51:36 (UTC+8)
Publisher:	FOOD & DRUG ADMINSTRATION
Abstract:	Cardiac hypertrophy is widely diagnosed in clinical cardiac disorders. The pathophysiology of hypertrophy is complex and multifactorial, a series of molecular and cellular changes are participated, such as activation of different signaling pathways, a switch of fetal gene program in the myocardium, and apoptosis. Some biomarkers have been applied to assess cardiac hypertrophy including atrial natriuretic peptides (ANP), brain/B-type natriuretic peptides (BNP), and alpha- or beta- Myosin Heavy Chain (MHC) in addition to others. Recently, ubiquitin-protein ligase E3A (UBE3A) has been observed to increase in cardiac hypertrophy. Therefore, UBE3A as a new biomarker seems valuable in the clinic. The cardiac hypertrophy is induced in rat-derived heart cell line H9c2 cells by potassium bromate (KBrO3), high glucose (HG), or isoproterenol (Iso), respectively. As an oxidizing agent, KBrO3 increased cell size at concentrations less than 250 mu M. Similarly, HG and Iso also induced cardiac hypertrophy in H9c2 cells. Interestingly, each kind of the cell models promoted the gene expression of the well-known biomarkers of cardiac hypertrophy including atrial natriuretic peptides (ANP) and brain/B- type natriuretic peptides (BNP). Additionally, UBE3A is also raised with the signals involved in cardiac hypertrophy such as calcineurin and nuclear factor of activated T-cells (NFAT) determined using Western blots. KBrO3 increased the protein levels of these signals and the specific inhibitor, such as cyclosporine A and tacrolimus, attenuated the signaling in H9c2 cells at concentrations sufficient to inhibit calcineurin in addition to the reduction of mRNA levels of UBE3A, similar to ANP or BNP. Moreover, HG or Iso also significantly increased protein levels of UBE3A in H9c2 cells. Taken together, we provided a new view that UBE3A is markedly raised in cardiac hypertrophy using various cell models, mainly through the activation of the calcineurin/NFAT signaling pathway in H9c2 cells. Therefore, UBE3A could be developed as a new biomarker in the diagnosis of cardiac hypertrophy. Copyright (C) 2018, Food and Drug Administration, Taiwan. Published by Elsevier Taiwan LLC.
Relation:	Journal of Food and Drug Analysis, v.27, n.1, pp. 355-364
Appears in Collections:	[Dept. of Pharmacy] Periodical Articles

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