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Dilek Colak, Ayodele A Alaiya, Namik Kaya, Nzioka P Muiya, Olfat AlHarazi, Zakia Shinwari, Editha Andres, Nduna Dzimiri
AIMS: The disease pathways leading to idiopathic dilated cardiomyopathy (DCM) are still elusive. The present study investigated integrated global transcriptional and translational changes in human DCM for disease biomarker discovery. METHODS: We used identical myocardial tissues from five DCM hearts compared to five non-failing (NF) donor hearts for both transcriptome profiling using the ABI high-density oligonucleotide microarrays and proteome expression with One-Dimensional Nano Acquity liquid chromatography coupled with tandem mass spectrometry on the Synapt G2 system...
2016: PloS One
Lijie Li, Wei Guo, Kui Wu, Yao Zhao, Qun Luo, Qingwu Zhang, Jianan Liu, Shaoxiang Xiong, Fuyi Wang
RATIONALE: Cox17 is a key copper chaperone protein responsible for delivery of cuprous ions to mitochondria and has been demonstrated to be involved in the anticancer action of cisplatin. However, the binding sites of the drug to the protein have not yet been directly identified. METHODS: The recombinant protein apo-Cox172s-s , the functional state of Cox17 transferring Cu(I), was reacted with an excess of cisplatin to produce platinated Cox17 adducts, of which the platination sites were identified by high-resolution Fourier transform ion cyclotron tandem mass spectrometry (FT-ICR-MS/MS) through electron capture dissociation (ECD)...
August 2016: Rapid Communications in Mass Spectrometry: RCM
Lijie Li, Wei Guo, Kui Wu, Xuelei Wu, Linhong Zhao, Yao Zhao, Qun Luo, Yuanyuan Wang, Yangzhong Liu, Qingwu Zhang, Fuyi Wang
Herein we report investigation of the interactions between anticancer organoruthenium complexes, [(η(6)-arene)Ru(en)(Cl)]PF6 (en=ethylenediamine, arene=p-cymene (1) or biphenyl (2)), and the human copper chaperone protein Cox17 by mass spectrometry with cisplatin as a reference. The electrospray ionization mass spectrometry (ESI-MS) results indicate much weaker binding of the ruthenium complexes than that of cisplatin to apo-Cox172s-s, the functional state of Cox17. Up to tetra-platinated Cox17 adducts were identified while only mono-ruthenated and a little amount of di-ruthenated Cox17 adducts were detected even for the reactions with 10-fold excess of the Ru complexes...
August 2016: Journal of Inorganic Biochemistry
Sergio A Muñoz-Gómez, Claudio H Slamovits, Joel B Dacks, Jeremy G Wideman
The MItochondrial Contact Site and Cristae Organizing System (MICOS) is required for the biogenesis and maintenance of mitochondrial cristae as well as the proper tethering of the mitochondrial inner and outer membranes. We recently demonstrated that the core components of MICOS, Mic10 and Mic60, are near-ubiquitous eukaryotic features inferred to have been present in the last eukaryote common ancestor. We also showed that Mic60 could be traced to α-proteobacteria, which suggests that mitochondrial cristae evolved from α-proteobacterial intracytoplasmic membranes...
November 2015: Communicative & Integrative Biology
Yaogang Zhong, Jing Zhang, Hanjie Yu, Jiaxu Zhang, Xiu-Xuan Sun, Wentian Chen, Huijie Bian, Zheng Li
Although the expression levels of total GalNAc-binding proteins (GNBPs) were up-regulated significantly in human hepatic stellate cells (HSCs) activated with transforming growth factor-β1(TGF-β1), yet little is known about the precise types, distribution and sub-cellular localization of the GNBPs in HSCs. Here, 264 GNBPs from the activated HSCs and 257 GNBPs from the quiescent HSCs were identified and annotated. A total of 46 GNBPs were estimated to be significantly up-regulated and 40 GNBPs were estimated to be significantly down-regulated in the activated HSCs...
December 25, 2015: Biochemical and Biophysical Research Communications
Christopher J Kershaw, Joseph L Costello, David Talavera, William Rowe, Lydia M Castelli, Paul F G Sims, Christopher M Grant, Mark P Ashe, Simon J Hubbard, Graham D Pavitt
The PUF family of RNA-binding proteins regulate gene expression post-transcriptionally. Saccharomyces cerevisiae Puf3p is characterised as binding nuclear-encoded mRNAs specifying mitochondrial proteins. Extensive studies of its regulation of COX17 demonstrate its role in mRNA decay. Using integrated genome-wide approaches we define an expanded set of Puf3p target mRNAs and quantitatively assessed the global impact of loss of PUF3 on gene expression using mRNA and polysome profiling and quantitative proteomics...
October 23, 2015: Scientific Reports
Yulia A Zatulovskaia, Ekaterina Y Ilyechova, Ludmila V Puchkova
Strong interest in copper homeostasis is due to the fact that copper is simultaneously a catalytic co-factor of the vital enzymes, a participant in signaling, and a toxic agent provoking oxidative stress. In mammals, during development copper metabolism is conformed to two types. In embryonic type copper metabolism (ETCM), newborns accumulate copper to high level in the liver because its excretion via bile is blocked; and serum copper concentration is low because ceruloplasmin (the main copper-containing protein of plasma) gene expression is repressed...
2015: PloS One
Lucila Garcia, Elina Welchen, Uta Gey, Agustín L Arce, Iris Steinebrunner, Daniel H Gonzalez
COX17 is a soluble protein from the mitochondrial intermembrane space that participates in the transfer of copper for cytochrome c oxidase (COX) assembly in eukaryotic organisms. In this work, we studied the function of both Arabidopsis thaliana AtCOX17 genes using plants with altered expression levels of these genes. Silencing of AtCOX17-1 in a cox17-2 knockout background generates plants with smaller rosettes and decreased expression of genes involved in the response of plants to different stress conditions, including several genes that are induced by mitochondrial dysfunctions...
March 2016: Plant, Cell & Environment
Lina J Nåbo, Charlotte S Madsen, Knud J Jensen, Jacob Kongsted, Kira Astakhova
Functionalized synthetic oligonucleotides are finding growing applications in research, clinical studies, and therapy. However, it is not easy to prepare them in a biocompatible and highly efficient manner. We report a new strategy to synthesize oligonucleotides with promising nucleic acid targeting and detection properties. We focus in particular on the pH sensitivity of these new probes and their high target specificity. For the first time, human copper(I)-binding chaperon Cox17 was applied to effectively catalyze click labeling of oligonucleotides...
May 26, 2015: Chembiochem: a European Journal of Chemical Biology
Magdalena Chojnacka, Agnieszka Gornicka, Silke Oeljeklaus, Bettina Warscheid, Agnieszka Chacinska
The mitochondrial contact site and cristae organizing system (MICOS) is a recently discovered protein complex that is crucial for establishing and maintaining the proper inner membrane architecture and contacts with the outer membrane of mitochondria. The ways in which the MICOS complex is assembled and its integrity is regulated remain elusive. Here, we report a direct link between Cox17, a protein involved in the assembly of cytochrome c oxidase, and the MICOS complex. Cox17 interacts with Mic60, thereby modulating MICOS complex integrity...
June 12, 2015: Journal of Biological Chemistry
Johanna R Koch, Franz X Schmid
Mia40 (a mitochondrial import and assembly protein) catalyzes disulfide bond formation in proteins in the mitochondrial intermembrane space. By using Cox17 (a mitochondrial copper-binding protein) as a natural substrate, we discovered that, in the presence of Mia40, the formation of native disulfides is strongly favored. The catalytic mechanism of Mia40 involves a functional interplay between the chaperone site and the catalytic disulfide. Mia40 forms a specific native disulfide in Cox17 much more rapidly than other disulfides, in particular, non-native ones, which originates from the recently described high affinity for hydrophobic regions near target cysteines and the long lifetime of the mixed disulfide...
December 12, 2014: Journal of Molecular Biology
David L Choveaux, Robert G E Krause, Jude M Przyborski, J P Dean Goldring
Copper is an essential micronutrient for all living organisms as an important catalytic co-factor for key enzymes. In higher eukaryotes intracellular copper is distributed by copper metallochaperones. Copper chelators such as neocuproine and tetrathiomolybdate inhibit Plasmodium falciparum erythrocytic development, indicating a requirement for copper by the parasite. A screen of the P. falciparum genome database identified eight potential copper-requiring protein orthologs, including four candidate copper metallochaperones implicated in the delivery of copper to cytochrome-c oxidase...
January 2015: Experimental Parasitology
Miao Sun, Xiao Zuo, Rui Li, Tao Wang, Y James Kang
Cardiomyocyte hypertrophy induced by phenylepherine (PE) is accompanied by depression of cytochrome c oxidase (COX) activity. Vascular endothelial growth factor (VEGF) recovers the suppressed COX activity and reverses cardiomyocyte hypertrophy. Because PE causes intracellular copper (Cu) depletion and COX activity is Cu-dependent, the present study was undertaken to test the hypothesis that VEGF recovers suppressed COX activity by restoring Cu availability. Primary cultures of neonatal rat cardiomyocytes were treated with PE at a final concentration of 100 µmol/L in cultures for 48 h to induce cell hypertrophy...
December 2014: Experimental Biology and Medicine
Robert P Favier, Bart Spee, Hille Fieten, Ted S G A M van den Ingh, Baukje A Schotanus, Bas Brinkhof, Jan Rothuizen, Louis C Penning
BACKGROUND: COMMD1-deficient dogs progressively develop copper-induced chronic hepatitis. Since high copper leads to oxidative damage, we measured copper metabolism and oxidative stress related gene products during development of the disease. METHODS: Five COMMD1-deficient dogs were studied from 6 months of age over a period of five years. Every 6 months blood was analysed and liver biopsies were taken for routine histological evaluation (grading of hepatitis), rubeanic acid copper staining and quantitative copper analysis...
January 2015: Journal of Trace Elements in Medicine and Biology
V Dermauw, A De Cuyper, L Duchateau, A Waseyehon, E Dierenfeld, M Clauss, I R Peters, G Du Laing, G P J Janssens
Copper deficiency is a commonly diagnosed problem in cattle around the globe. In Jimma, Ethiopia, 8 zebu (Bos indicus) and 8 zebu ×: Holstein Friesian cross (Bos taurus ×: Bos indicus) heifers were used in an 11-wk study to investigate breed type differences and effects of Cu deficiency on concentrations of trace elements in plasma and edible tissues as well as mRNA expression of Cu-related genes. Heifers were fed a grass diet (6.4 ± 0.2 [SEM] mg Cu/kg DM) supplemented with 1 mg Mo/kg DM in wk 1 to 4 and 2 mg Mo/kg DM in wk 5 to 11, with blood samples collected every 2 wk and tissue collection postmortem...
July 2014: Journal of Animal Science
Linhong Zhao, Qinqin Cheng, Zhen Wang, Zhaoyong Xi, Dechen Xu, Yangzhong Liu
Cox17 facilitates the platinum accumulation in mitochondria, which contributes to the overall cytotoxicity of cisplatin.
March 11, 2014: Chemical Communications: Chem Comm
Johanna R Koch, Franz X Schmid
Mia40 catalyses the oxidative folding of disulphide-containing proteins in the mitochondria. The folding pathway is directed by the formation of the first mixed disulphide between Mia40 and its substrate. Here, we employ Cox17 to elucidate the molecular determinants of this reaction. Mia40 engages initially in a dynamic non-covalent enzyme-substrate complex that forms and dissociates within milliseconds. Cys36 of Cox17 forms the mixed disulphide in an extremely rapid reaction that is limited by the preceding complex formation with Mia40...
2014: Nature Communications
Melanie A Miller, Joseph Russo, Anthony D Fischer, Florencia A Lopez Leban, Wendy M Olivas
The Puf family of RNA-binding proteins regulates gene expression primarily by interacting with the 3' untranslated region (3' UTR) of targeted mRNAs and inhibiting translation and/or stimulating decay. Physical association and computational analyses of yeast Puf3p identified >150 potential mRNA targets involved in mitochondrial function. However, only COX17 has been established as a target of Puf3p-mediated deadenylation and decapping. We have identified 10 new targets that are rapidly degraded in a Puf3p-dependent manner...
April 2014: Nucleic Acids Research
Daoyin Dong, Xinhua Xu, Wen Yin, Y James Kang
Copper chaperones are critical regulators of intracellular copper metabolism and distribution. The present study was undertaken to investigate the effects of changes in copper concentrations on the abundance of copper chaperones. Human umbilical vein endothelial cells (HUVECs) were treated with siRNA targeting copper transporter 1 (CTR1) or tetraethylenepentamine (TEPA) to decrease, or with copper sulfide to increase, intracellular copper concentrations, assayed using an atomic absorption spectrophotometer...
March 2014: Metallomics: Integrated Biometal Science
Daoyin Dong, Biao Wang, Wen Yin, Xueqing Ding, Jingjing Yu, Y James Kang
Elevation of serum homocysteine (Hcy) levels is a risk factor for cardiovascular diseases. Previous studies suggested that Hcy interferes with copper (Cu) metabolism in vascular endothelial cells. The present study was undertaken to test the hypothesis that Hcy-induced disturbance of Cu homeostasis leads to endothelial cell injury. Exposure of human umbilical vein endothelial cells (HUVECs) to concentrations of Hcy at 0.01, 0.1 or 1 mM resulted in a concentration-dependent decrease in cell viability and an increase in necrotic cell death...
2013: PloS One
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