Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones

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	Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones
	Liu, Yan 1; Yan, Xing 2; Mao, Guangmei 1; Fang, Li 1; Zhao, Beilei 1; Liu, Yahan 1; Tang, Huiru 2; Wang, Nanping 1,3
刊名	JOURNAL OF PROTEOME RESEARCH
	2013-12-01
卷号	12 期号:12 页码:5634-5641
关键词	thiazolidinediones PPARy cardiac hypertrophy metabonomics purine nucleotide metabolism
英文摘要	Thiazolidinediones (TZDs) including rosiglitazone (RSG) and pioglitazone (PIO) are synthetic agonists selective for peroxisome proliferator-activated receptor-gamma (PPAR gamma) and have been clinically used to treat type-II diabetes as insulin sensitizers. Recent meta-analyses have shown that TZDs are associated with an increased risk for the development of heart failure. To elucidate the mechanism underlying such a cardiac adverse effect, we used a H-1 NMR-based approach to examine the metabonomic profiles in the cardiac tissues treated with RSG (15 mg/kg body weight/day) or PIO (45 mg/kg/day) for 4 weeks and found that the TZD treatments resulted in a significantly altered metabolic profile in hearts, which was associated with cardiac hypertrophy. Multivariate analysis demonstrated that TZDs led to an accumulation in adenosine monophosphate (AMP) and a depletion of inosine. Consistently, AMP kinase, a signal pathway sensitive to the change in the intracellular concentrations of AMP, was activated in the cardiac tissues from the TZDs-treated rats. Quantitative real-time reverse-transcriptase polymerase chain reaction showed a significant induction of the genes involved in the de novo synthesis of purine nucleotide but a reduction of those for the catabolism. Furthermore, the putative PPAR-responsive elements were identified in the 5 '-flanking regions of the TZD-up-regulated genes such as adenylosuccinate synthase gene (Adss) and phosphoribosl pyrophosphate synthetase 1 (Prpsl), and the binding of PPAR gamma to these motifs was confirmed by using chromatin immunoprecipitation assay. In conclusion, these results demonstrated that TZDs induced alterations in purine nucleotide metabolism in rat hearts via transcriptional regulation of the PPAR gamma-target genes, which may play an important role in the development of cardiac hypertrophy associated with TZDs.
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Biochemical Research Methods
研究领域[WOS]	Biochemistry & Molecular Biology
关键词[WOS]	ACTIVATED PROTEIN-KINASE ; DEHYDROGENASE-DERIVED NADPH ; HEART-FAILURE ; SUPEROXIDE-PRODUCTION ; SIGNALING PATHWAYS ; RECEPTOR-GAMMA ; FAILING HEART ; ROSIGLITAZONE ; GENE ; AGONIST
收录类别	SCI
语种	英语
WOS记录号	WOS:000328231300025
内容类型	期刊论文
源URL	[http://ir.wipm.ac.cn/handle/112942/830]
专题	武汉物理与数学研究所_磁共振应用研究部
作者单位	1.Peking Univ, Hlth Sci Ctr, Inst Cardiovasc Sci, Beijing 100191, Peoples R China 2.Chinese Acad Sci, Key Lab Magnet Resonance Biol Syst, State Key Lab Magnet Resonance & Atom & Mol Phys, Wuhan Ctr Magnet Resonance,Wuhan Inst Phys & Math, Wuhan 430071, Peoples R China 3.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian 710061, Peoples R China
推荐引用方式 GB/T 7714	Liu, Yan,Yan, Xing,Mao, Guangmei,et al. Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones[J]. JOURNAL OF PROTEOME RESEARCH,2013,12(12):5634-5641.
APA	Liu, Yan.,Yan, Xing.,Mao, Guangmei.,Fang, Li.,Zhao, Beilei.,...&Wang, Nanping.(2013).Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones.JOURNAL OF PROTEOME RESEARCH,12(12),5634-5641.
MLA	Liu, Yan,et al."Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones".JOURNAL OF PROTEOME RESEARCH 12.12(2013):5634-5641.