Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages

	Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages
	Deng, WJ; Nie, S; Dai, J; Wu, JR; Zeng, R
刊名	MOLECULAR & CELLULAR PROTEOMICS
	2010
卷号	9 期号:1 页码:100-116
通讯作者	Zeng, R (reprint author), Chinese Acad Sci, Key Lab Syst Biol, Inst Biochem & Cell Biol, Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China.,zr@sibs.ac.cn
英文摘要	It has been proposed that mitochondrial dysfunction is involved in the pathogenesis of type 2 diabetes (T2D). To dissect the underlying mechanisms, we performed a multiplexed proteomics study on liver mitochondria isolated from a spontaneous diabetic rat model before/after they were rendered diabetic. Altogether, we identified 1091 mitochondrial proteins, 228 phosphoproteins, and 355 hydroxyproteins. Mitochondrial proteins were found to undergo expression changes in a highly correlated fashion during T2D development. For example, proteins involved in beta-oxidation, the tricarboxylic acid cycle, oxidative phosphorylation, and other bioenergetic processes were coordinately up-regulated, indicating that liver cells confronted T2D by increasing energy expenditure and activating pathways that rid themselves of the constitutively increased flux of glucose and lipid. Notably, activation of oxidative phosphorylation was immediately related to the overproduction of reactive oxygen species, which caused oxidative stress within the cells. Increased oxidative stress was also evidenced by our post-translational modification profiles such that mitochondrial proteins were more heavily hydroxylated during T2D development. Moreover, we observed a distinct depression of antiapoptosis and antioxidative stress proteins that might reflect a higher apoptotic index under the diabetic stage. We suggest that such changes in systematic metabolism were causally linked to the development of T2D. Comparing proteomics data against microarray data, we demonstrated that many T2D-related alterations were unidentifiable by either proteomics or genomics approaches alone, underscoring the importance of integrating different approaches. Our compendium could help to unveil pathogenic events in mitochondria leading to T2D and be useful for the discovery of diagnosis biomarker and therapeutic targets of T2D. Molecular & Cellular Proteomics 9: 100-116, 2010.
学科主题	Biochemistry & Molecular Biology
类目[WOS]	Biochemical Research Methods
关键词[WOS]	TANDEM MASS-SPECTROMETRY ; 2-DIMENSIONAL LIQUID-CHROMATOGRAPHY ; HMG-COA SYNTHASE ; INSULIN-RESISTANCE ; SKELETAL-MUSCLE ; PYRUVATE-DEHYDROGENASE ; OXIDATIVE STRESS ; GENE-EXPRESSION ; GK RAT ; MELLITUS
收录类别	SCI
语种	英语
WOS记录号	WOS:000275505900008
内容类型	期刊论文
版本	出版稿
源URL	[http://202.127.25.143/handle/331003/934]
专题	上海生化细胞研究所_上海生科院生化细胞研究所
推荐引用方式 GB/T 7714	Deng, WJ,Nie, S,Dai, J,et al. Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages[J]. MOLECULAR & CELLULAR PROTEOMICS,2010,9(1):100-116.
APA	Deng, WJ,Nie, S,Dai, J,Wu, JR,&Zeng, R.(2010).Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages.MOLECULAR & CELLULAR PROTEOMICS,9(1),100-116.
MLA	Deng, WJ,et al."Proteome, Phosphoproteome, and Hydroxyproteome of Liver Mitochondria in Diabetic Rats at Early Pathogenic Stages".MOLECULAR & CELLULAR PROTEOMICS 9.1(2010):100-116.