TY - JOUR
T1 - Comparative proteomics study on liver mitochondria of primary biliary cirrhosis mouse model
AU - Song, Guang
AU - Hu, Chaojun
AU - Zhu, Huishan
AU - Li, Xi
AU - Zhao, Liying
AU - Zhou, Renfang
AU - Zhang, Xuan
AU - Zhang, Fengchun
AU - Wu, Lin
AU - Li, Yongzhe
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Science and Technology of the People’s Republic of China (2009CB522204, and 2011AA02A113); the National Natural Science Foundation of China (30971447, 30872331 and 81072486), and the Ministry of Health of China (Key Clinical Program 2010–2012). The authors thank Ijeoma Uzoma from Department of Pharmacology & HiT Center of Johns Hopkins University School of Medicine for text editing.
PY - 2013/4/12
Y1 - 2013/4/12
N2 - Background: Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC.Methods: Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting.Results: In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated.Conclusions: iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC.
AB - Background: Primary biliary cirrhosis (PBC) is a liver specific chronic disease with unclear pathogenesis, especially for the early stage molecular events. The mitochondrion is a multi-functional organelle associated with various diseases including PBC. The purpose of this study was to discover the alterations in the mitochondria proteome using an early stage PBC mouse model for revealing the possible pathogenesis mechanisms in the early stages of PBC.Methods: Mouse model of early stage of PBC was constructed by consecutive administration of poly I:C. Mitochondria of mouse models and controls were purified and comparative proteomics was performed by iTRAQ technology. Then, differentially expressed proteins were validated by western blotting.Results: In total 354 proteins that satisfied the criteria for comparative proteomics study were identified. Of them, nine proteins were downregulated and 20 were up-regulated in liver mitochondria of PBC mouse model. Most differentially expressed proteins are associated with oxidation-reduction and lipid metabolism, and some are involved in the biosynthesis of steroid hormone and primary bile acid. Interestingly, four proteins (HCDH, CPT I, DECR, ECHDC2) involved in the fatty acid beta-oxidation were all upregulated.Conclusions: iTRAQ is a powerful tool for comparative proteomics study of PBC mouse model and differentially expressed proteins in mitochondria proteome of PBC mouse model provide insights for the pathogenesis mechanism at early stage of PBC.
KW - Molecular pathogenesis
KW - Primary biliary cirrhosis
KW - Proteomics
KW - iTRAQ
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U2 - 10.1186/1471-230X-13-64
DO - 10.1186/1471-230X-13-64
M3 - Article
C2 - 23586776
AN - SCOPUS:84876979613
VL - 13
JO - BMC Gastroenterology
JF - BMC Gastroenterology
SN - 1471-230X
IS - 1
M1 - 64
ER -