Cox17

Diagnosis of Wilson disease (WD) can be difficult because of its protean clinical presentations, but early diagnosis is important because effective treatment is available and can prevent disease progression. Similarly, diagnosis of WD on liver biopsy specimens is difficult due to the wide range of histologic appearances. A stain that could help identify WD patients would be of great value. The goal of this study was to use mass spectrometry-based proteomics to identify potential proteins that are differentially expressed in WD compared to controls, and could serve as potential immunohistochemical markers for screening...

Copper serves as a co-factor for a host of metalloenzymes that contribute to malignant progression. The orally bioavailable copper chelating agent tetrathiomolybdate (TM) has been associated with a significant survival benefit in high-risk triple negative breast cancer (TNBC) patients. Despite these promising data, the mechanisms by which copper depletion impacts metastasis are poorly understood and this remains a major barrier to advancing TM to a randomized phase II trial. Here, using two independent TNBC models, we report a discrete subpopulation of highly metastatic SOX2/OCT4+ cells within primary tumors that exhibit elevated intracellular copper levels and a marked sensitivity to TM...

Despite the economic importance of creating cold resilient cattle breeds, our knowledge of the genetic basis of adaptation to cold environments in cattle is still scarce compared to information on other economically important traits. Herein, using whole-genome resequencing of animals showing contrasting phenotypes on temperature maintenance under acute cold stress combined with the existing SNP (single nucleotide polymorphism) functional annotations, we report chromosomal regions and candidate SNPs controlling body temperature in the Siberian cattle populations...

Aspergillus fumigatus is the leading cause of life-threatening invasive mold infections in immunocompromised individuals. This ubiquitous saprophyte possesses several natural attributes allowing it to evade the immune system, including the ability to withstand high toxic Cu concentrations within the phagosomes of macrophages and neutrophils. We previously established that at high levels, Cu binds and activates the A. fumigatus transcription factor AceA, which upregulates the expression of the Cu exporter CrpA to expel excess Cu...

The objectives of these experiments were to investigate (1) the relative abundance of transcripts for Cu-responsive genes in whole bovine liver vs. cultured hepatocytes and (2) the influence of Cu dose on the relative abundance of transcripts for Cu-responsive genes in cultured bovine hepatocytes. Experiment 1: Liver samples were obtained immediately post-mortem from one healthy Angus steer. Half of the tissue samples were placed in RNAlater solution; the remaining half was used to isolate hepatocytes. Experiment 2: A subset of cultured hepatocytes was incubated in media containing: 0 mg/L, 0...

Background: T89 , a traditional Chinese medicine, has passed phase II, and is undergoing phase III clinical trials for treatment of ischemic cardiovascular disease by the US FDA. However, the role of T89 on isoproterenol (ISO)-induced cardiac injury is unknown. The present study aimed to explore the effect and underlying mechanism of T89 on ISO-induced cardiac injury. Methods: Male Sprague-Dawley rats received subcutaneous injection of ISO saline solution at 24 h intervals for the first 3 days and then at 48 h intervals for the next 12 days...

Copper deficiency (CuD) is a common cause of oxidative cardiac tissue damage in ruminants. The expression of copper chaperone (Cu-Ch) encoding genes enables an in-depth understanding of copper-associated disorders, but no previous studies have been undertaken to highlight Cu-Ch disturbances in heart tissue in ruminants due to CuD. The current study aimed to investigate the Cu-Ch mRNA expression in the heart of goats after experimental CuD and highlight their relationship with the cardiac measurements. Eleven male goats were enrolled in this study and divided into the control group (n = 4) and CuD group (n = 7), which received copper-reducing dietary regimes for 7 months...

Unbalanced copper (Cu2+ ) homeostasis is associated with the developmental defects of vertebrate myogenesis, but the underlying molecular mechanisms remain elusive. In this study, it was found that Cu2+ stressed zebrafish embryos and larvae showed reduced locomotor speed as well as loose and decreased myofibrils in skeletal muscle, coupled with the downregulated expression of muscle fiber markers mylpfa and smyhc1l and the irregular arrangement of myofibril and sarcomere. Meanwhile, the Cu2+ stressed zebrafish embryos and larvae also showed significant reduction in the expression of H3K4 methyltransferase smyd1b transcripts and H3K4me3 protein as well as in the binding enrichment of H3K4me3 on gene mylpfa promoter in skeletal muscle cells, suggesting that smyd1b-H3K4me3 axis mediates the Cu2+ -induced myofibrils specification defects...

Overexpressed gastrin is reported to promote oncogenesis and development of gastric cancer by inhibiting apoptosis of cancer cells; however, the underlying mechanism remains unclear. Our study is aimed at revealing the mechanism underlying the effect of gastrin on apoptosis of gastric cancer cells. Gastrin-interfering cell line was constructed by stably transfecting gastrin-specific pshRNA plasmid to gastric cancer cell line BGC-823. Then, differentially expressed proteins between untreated BGC-823 and gastrin-interfering BGC-823 cell lines were detected by the iTRAQ technique...

Mitochondrial biogenesis relies on different protein import machinery, as mitochondrial proteins are imported from the cytosol. The mitochondrial intermembrane space assembly (MIA) pathway consists of GFER/ALR and CHCHD4/Mia40, responsible for importing proteins and their oxidative folding inside the mitochondria. The MIA pathway plays an essential role in complex IV (COX IV) biogenesis via importing copper chaperone COX17, associated with the respiratory chain. BPA, an environmental toxicant, found in consumable plastics, causes neurotoxicity via impairment in mitochondrial dynamics, neurogenesis, and cognitive functions...

Epilepsy can severely affect the quality of life of patients, who are often at higher risk of mortality. However, the molecular mechanisms and pathogenesis underlying epileptogenesis are poor understood. In this study, we performed a proteomic analysis of the hippocampus in pentylenetetrazole (PTZ)-kindled epileptic rats to explore the molecular mechanisms of epileptogenesis. We established an epileptic model in Sprague-Dawley rats by injecting PTZ intraperitoneally and applied isobaric tags for relative and absolute quantification (iTRAQ) technology integrated with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to identify differentially expressed proteins (DEPs) in the hippocampus...

Copper is an essential element in all forms of life. It acts as a cofactor of some enzymes and is involved in forming proper protein conformations. However, excess copper ions in cells are detrimental as they can generate free radicals or disrupt protein structures. Therefore, all life forms have evolved conserved and exquisite copper metabolic systems to maintain copper homeostasis. The yeast Saccharomyces cerevisiae has been widely used to investigate copper metabolism as it is convenient for this purpose...

Thiacloprid is widely used in agriculture and may affect pollinators. However, its molecular effects are poorly known. Here, we report the global gene expression profile in the brain of honey bee foragers assessed by RNA-sequencing. Bees were exposed for 72 h to nominal concentrations of 25 and 250 ng/bee via sucrose solution. Determined residue concentrations by LC-MS/MS were 0.59 and 5.49 ng/bee, respectively. Thiacloprid exposure led to 5 and 71 differentially expressed genes (DEGs), respectively. Nuclear genes encoding mitochondrial ribosomal proteins and enzymes involved in oxidative phosphorylation, as well as metabolism enzymes and transporters were altered at 5...

Unbalanced copper (Cu) homeostasis is associated with neurological development defects and diseases. However, the molecular mechanisms remain elusive. Here, central neural system (CNS) myelin defects and the down-regulated expression of WNT/NOTCH signaling and its down-stream mediator hoxb5b were observed in Cu2+ stressed zebrafish larvae. The loss/knockdown-of-function of hoxb5b phenocopied the myelin and axon defects observed in Cu2+ stressed embryos. Meanwhile, the activation of WNT/NOTCH signaling and ectopic expression of hoxb5b could rescue Cu induced myelin defects...

Leukemic stem cells (LSCs) rely on oxidative metabolism and are differentially sensitive to targeting mitochondrial pathways, which spares normal hematopoietic cells. A subset of mitochondrial proteins is folded in the intermembrane space via the mitochondrial intermembrane assembly (MIA) pathway. We found increased mRNA expression of MIA pathway substrates in acute myeloid leukemia (AML) stem cells. Therefore, we evaluated the effects of inhibiting this pathway in AML. Genetic and chemical inhibition of ALR reduces AML growth and viability, disrupts LSC self-renewal, and induces their differentiation...

Aquatic pollution is one of the most common threats to the ecological health of aquatic ecosystems and its biota. Fish as lower vertebrates are excellent model to study the impact and responses of aquatic pollution. In fish, gill is the main organ indicator of whole animal health as it comes in contact with the surrounding water and absorbs many pollutants and contaminants; therefore, investigations on alterations in fish gill at transcriptome level could provide newer insights to the stress response mechanism(s) and pathways...

Fluorescence-based chelators are commonly used to probe labile low-molecular-mass (LMM) metal pools in the cytosol of eukaryotic cells, but such chelators destroy the complexes of interest during detection. The objective of this study was to use chromatography to directly detect such complexes. Towards this end, 47 batches of cytosol were isolated from fermenting S. cerevisiae yeast cells and passed through a 10 kDa cut-off membrane. The metal contents of the cytosol and resulting flow-through solution (FTS) were determined...

PURPOSE: To investigate the associations between single-nucleotide polymorphisms (SNPs) in the lysyl oxidase-like 1 (LOXL1) gene and copper chaperone genes and pseudoexfoliation-syndrome-related cataract (PEXC) in a Chinese Uygur population. METHODS: A case-control study was performed at the Second People's Hospital of Kashgar. Venous blood DNA was obtained from 70 patients with PEXC and 70 patients with age-related cataract (ARC). The exonic sequences of the LOXL1, antioxidant 1 copper chaperone (ATOX1), cytochrome C oxidase 17 copper chaperone (COX17), and copper chaperone for superoxide dismutase (CCS) genes were determined by Sanger sequencing, followed by a genetic association study...

BACKGROUND: The disorder of copper homeostasis is linked with disease and developmental defects, and excess copper_nanoparticles (CuNPs) and ion (Cu2+ ) will induce developmental malformation and disease in organisms. However, little knowledge is available regarding its potential regulation mechanisms, and little study links excess copper with retinal developmental malformation and disease. METHODS: Embryos were stressed with copper (CuNPs and Cu2+ ), and cell proliferation and apoptosis assays, reactive oxygen species (ROS) and endoplasmic reticulum (ER) signaling detections, and genetic mutants cox17-/- and atp7a-/- application, were used to evaluate copper induced retinal developmental malformation and the underlying genetic and biological regulating mechanisms...

Endothelin-1 (ET-1) is a vasoactive peptide that is elevated in aqueous humor as well as circulation of primary open angle glaucoma (POAG) patients. ET-1 has been shown to promote degeneration of optic nerve axons and apoptosis of retinal ganglion cells (RGCs), however, the precise mechanisms are still largely unknown. In this study, RNA-seq analysis was used to assess changes in ET-1 mediated gene expression in primary RGCs, which revealed that 23 out of 156 differentially expressed genes (DEGs) had known or predicted mitochondrial function, of which oxidative phosphorylation emerged as the top-most enriched pathway...