title: Quantitative proteomic study of myocardial mitochondria in urea transporter B knockout mice.
abstract: In previous research, we showed that 16-week-old urea transporter B (UT-B) null mice have an atrial-ventricular conduction block, and hypothesized myocardial mitochondrial dysfunction. To investigate the mechanism of this block, we examined the proteomic differences in the myocardial mitochondria of UT-B null and wild-type mice with nanoscale LC-MS/MS. Of 26 proteins clearly downregulated in the UT-B null mice, 15 are involved in complexes I, III, IV, and V of the respiratory chain, which would strongly reduce the activity of the electron transport chain. Excess electrons from complexes I and III pass directly to O2 to generate ROS and deplete ROS-scavenging enzymes. Myocardial intracellular ROS were significantly higher in UT-B null mice than in wild-type mice (p < 0.01), constituting an important cause of oxidative stress injury in the myocardia of UT-B null mice. The mitochondrial membrane potential (ΔΨm) was also lower in UT-B null mice than in wild-type mice (p < 0.05), causing oxidative phosphorylation dysfunction of complex V and insufficient ATP in the myocardial cells of UT-B null mice. HADHA (a trifunctional protein) and HSP60 were also downregulated in the UT-B null myocardial mitochondria. These results confirm that mitochondrial dysfunction underlies the pathogenesis of the atrial-ventricular conduction block in UT-B null mice.
authors.affiliation: Key Laboratory of Pathobiology, Department of Pathophysiology, Ministry of Education, College of Basic Medicine, Jilin University, Changchun, P. R. China.
authors.forename: Yanwei
authors.initials: Y
authors.lastname: Du
authors.forename: Yan
authors.initials: Y
authors.lastname: Meng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
authors.forename: Le
authors.initials: L
authors.lastname: Kang
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Jia
authors.forename: Lirong
authors.initials: L
authors.lastname: Guo
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Mingliang
authors.initials: M
authors.lastname: Ye
authors.forename: Lianghai
authors.initials: L
authors.lastname: Hu
authors.forename: Xuejian
authors.initials: X
authors.lastname: Zhao
authors.forename: Jingkai
authors.initials: J
authors.lastname: Gu
authors.forename: Baoxue
authors.initials: B
authors.lastname: Yang
authors.forename: Hanfa
authors.initials: H
authors.lastname: Zou
mesh_terms: D000818:Animals; D055786:Gene Knockout Techniques; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008929:Mitochondria, Heart / Q000737:chemistry / Q000378:metabolism*; D020543:Proteome / Q000032:analysis* / Q000235:genetics*; D040901:Proteomics / Q000379:methods*; D000096982:Urea Transporters
chemical_list: D026901:Membrane Transport Proteins; D020543:Proteome; D000096982:Urea Transporters
keywords: Animal proteomics; Heart; Mitochondria; Urea transporter