Metabonomic Profiling Revealed an Alteration in Purine Nucleotide Metabolism Associated with Cardiac Hypertrophy in Rats Treated with Thiazolidinediones
文献类型：期刊论文
| 作者 | Liu, Yan1; Yan, Xing2; Mao, Guangmei1; Fang, Li1; Zhao, Beilei1; Liu, Yahan1; Tang, Huiru2; Wang, Nanping1,3 |
| 刊名 | JOURNAL OF PROTEOME RESEARCH
 |
| 出版日期 | 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 |
| 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. |
入库方式： OAI收割
来源：武汉物理与数学研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。