Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice

doi:10.1042/BCJ20190105

科研成果详情

题名	Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice
作者	Li, Chen 1; Niu, Yan1; Zheng, Hong1; Shan, Congjia 2; Chen, Qinbo 1; Yang, Zhongzhou 2; Zhao, Liangcai1; Yang, Changwei 1; Gao, Hongchang1
发表日期	2019-07-15
发表期刊	BIOCHEMICAL JOURNAL 影响因子和分区
语种	英语
原始文献类型	Article
关键词	PDK1 heart failure metabolic remodeling metabolomics mitochondrial respiration.
其他关键词	HEART-FAILURE ; PDK1 ; DEFICIENCY
摘要	Metabolic remodeling plays an essential role in the pathophysiology of heart failure (HF). Many studies have shown that the disruption of phosphoinositide-dependent protein kinase-1 (PDK1) caused severe and lethal HF; however, the metabolic pattern of PDK1 deletion remains ambiguous. H-1 nuclear magnetic resonance-based metabolomics was applied to explore the altered metabolic pattern in Pdk1-deficient mice. Principle component analysis showed significant separation as early as 4 weeks of age, and dysfunction of metabolism precedes a morphological change in Pdk1-deficient mice. A time trajectory plot indicated that disturbed metabolic patterns were related to the pathological process of the HF in Pdk1-deficient mice, rather than the age of mice. Metabolic profiles demonstrated significantly increased levels of acetate, glutamate, glutamine, and O-phosphocholine in Pdk1 deletion mice. Levels of lactate, alanine, glycine, taurine, choline, fumarate, IMP, AMP, and ATP were significantly decreased compared with controls. Furthermore, PDK1 knockdown decreased the oxygen consumption rate in H9C2 cells as determined using a Seahorse XF96 Analyzer. These findings imply that the disruption of metabolism and impaired mitochondrial activity might be involved in the pathogenesis of HF with PDK1 deletion.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81771386, 21575105, 81770830]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LQ18H160027, LY17H160049]
出版者	PORTLAND PRESS LTD
出版地	LONDON
ISSN	0264-6021
EISSN	1470-8728
卷号	476 期号:13 页码:1943-1954
DOI	10.1042/BCJ20190105
页数	12
WOS类目	Biochemistry & Molecular Biology
WOS研究方向	Biochemistry & Molecular Biology
WOS记录号	WOS:000476475900007
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	31208986
SCOPUSEID	2-s2.0-85069329374
通讯作者地址	[Li, Chen]School of Pharmaceutical Sciences,Institute of Metabonomics and Medical NMR,Wenzhou Medical University,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Molecular Biology;Cell Biology
引用统计	被引频次[WOS]：0 [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/18182
专题	附属第二医院_核磁共振室药学院（分析测试中心）
通讯作者	Li, Chen
作者单位	1.School of Pharmaceutical Sciences,Institute of Metabonomics and Medical NMR,Wenzhou Medical University,Wenzhou,325035,China; 2.Model Animal Research Center of Nanjing University,Nanjing,210061,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Li, Chen,Niu, Yan,Zheng, Hong,et al. Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice[J]. BIOCHEMICAL JOURNAL,2019,476(13):1943-1954.
APA	Li, Chen., Niu, Yan., Zheng, Hong., Shan, Congjia., Chen, Qinbo., ... & Gao, Hongchang. (2019). Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice. BIOCHEMICAL JOURNAL, 476(13), 1943-1954.
MLA	Li, Chen,et al."Metabolic remodeling of cardiomyocytes identified in phosphoinositide-dependent kinase 1-deficient mice".BIOCHEMICAL JOURNAL 476.13(2019):1943-1954.