Copper chaperone

Antioxidant 1 copper chaperone (Atox1) may contribute to preventing DDP cochlear damage by regulating copper transport family and cell cycle proteins. A rat model of cochlear damage was developed by placing gelatin sponges treated with DDP in the cochlea. HEI-OC1 cells were treated with 133 μM DDP as a cell model. DDP-induced ototoxicity in rats was confirmed by immunofluorescence (IF) imaging. The damage of DDP to HEI-OC1 cells was assessed by using CCK-8, TUNEL, and flow cytometry. The relationship between Atox1, a member of the copper transport protein family, and the damage to in vivo / vitro models was explored by qRT-PCR, western blot, CCK-8, TUNEL, and flow cytometry...

Hepatocellular carcinoma (HCC) is one of the most common and deadly cancers in the world. The therapeutic outlook for HCC patients has significantly improved with the advent and development of systematic and targeted therapies such as sorafenib and lenvatinib; however, the rise of drug resistance and the high mortality rate necessitate the continuous discovery of effective targeting agents. To discover novel anti-HCC compounds, we first constructed a deep learning-based chemical representation model to screen more than 6 million compounds in the ZINC15 drug-like library...

Transition metal ions, such as copper, are indispensable components in the biological system. Copper ions which primarily exist in two major oxidation states Cu(I) and Cu(II) play crucial roles in various cellular processes including antioxidant defense, biosynthesis of neurotransmitters, and energy metabolism, owing to their inherent redox activity. The disturbance in copper homeostasis can contribute to the development of copper metabolism disorders, cancer, and neurodegenerative diseases, highlighting the significance of understanding the copper trafficking system in cellular environments...

Accumulating evidence suggests that superoxide dismutase (SOD) is the first line of antioxidant defense in organisms and plays an important role in scavenging reactive oxygen species produced during environmental stress. However, limited information is available regarding the response of SOD genes to cold stress in ticks. Therefore, in the present study, SOD genes were cloned and identified from the genome of Haemaphysalis longicornis, and the function of SOD during the cold response was further explored. Seven SOD genes were characterized: HlCCS1, HlCCS2, HlMSD, HlCSD1, HlCSD2, HlCSD3, and HlCSD4...

Copper (Cu) is a vital trace element for maintaining human health. Current evidence suggests that genes responsible for regulating copper influx and detoxification help preserve its homeostasis. Adequate Cu levels sustain normal cardiac and blood vessel activity by maintaining mitochondrial function. Cuproptosis, unlike other forms of cell death, is characterized by alterations in mitochondrial enzymes. Therapeutics targeting cuproptosis in cardiovascular diseases (CVDs) mainly include copper chelators, inhibitors of copper chaperone proteins, and copper ionophores...

The polyphenolic component of citrus fruits, hesperetin (Hst), is a metabolite of hesperidin. In this study, we examined the effect of varying doses and exposure times of hesperetin on MCF-7 and MDA-MB-231 cancer cells, as well as MCF-10A normal cells. By using MTT assay, real-time PCR, western blot, and flow cytometry, we determined the effects of Hst on cell viability, ROS levels, and markers of cell death. Furthermore, molecular docking was used to identify Hst targets that might be involved in ROS-dependent cell death...

A new heteroleptic copper(II) compound named C0-UDCA was prepared by reaction of [Cu(phen)2 (OH2 )](ClO4 )2 (C0) with the bile ursodeoxycholic acid (UDCA). The resulting compound is able to inhibit the lipoxygenase enzyme showing more efficacy than the precursors C0 and UDCA. Molecular docking simulations clarified the interactions with the enzyme as due to allosteric modulation. The new complex shows antitumoral effect on ovarian (SKOV-3) and pancreatic (PANC-1) cancer cells at the Endoplasmic Reticulum (ER) level by activating the Unfolded Protein Response...

The first phosphorus dendrimers built on a cyclotriphosphazene core and decorated with six or twelve monofluorocyclooctyne units were prepared. A simple stirring allowed the grafting of N-hexyl deoxynojirimycin inhitopes onto their surface by copper-free strain promoted alkyne-azide cycloaddition click reaction. The synthesized iminosugars clusters were tested as multivalent inhibitors of the biologically relevant enzymes β-glucocerebrosidase and acid α-glucosidase, involved in Gaucher and Pompe lysosomal storage diseases, respectively...

The imbalance in metal homeostasis can be associated with several human diseases, and exposure to increasing concentrations of metals promotes cell stress and toxicity. Therefore, understanding the cytotoxic effect of metal imbalance is important to unravel the biochemical mechanism of homeostasis and the action of potential protective proteins against metal toxicity. Several studies, including gene deletion in yeast, provide evidence indicating the possible indirect involvement of cochaperones from the Hsp40/DNAJA family in metal homeostasis, possibly through modulating the activity of Hsp70...

INTRODUCTION: Spinal cord injury (SCI) is a severe central nervous system injury that leads to significant sensory and motor impairment. Copper, an essential trace element in the human body, plays a vital role in various biological functions and is strictly regulated by copper chaperones and transporters. Cuproptosis, a novel type of metal ion-induced cell death, is distinct from iron deprivation. Copper deprivation is closely associated with mitochondrial metabolism and mediated by protein fatty acid acylation...

Renal fibrosis relies on multiple proteins and cofactors in its gradual development. Copper is a cofactor of many enzymes involved in renal microenvironment homeostasis. We previously reported that intracellular copper imbalance occurred during renal fibrosis development and was correlated with fibrosis intensity. In this study, we investigated the molecular mechanisms of how copper affected renal fibrosis development. Unilateral ureteral obstruction (UUO) mice were used for in vivo study; rat renal tubular epithelial cells (NRK-52E) treated with TGF-β1 were adapted as an in vitro fibrotic model...

Due to the similarity in the basic coordination behavior of their mono-charged cations, silver biochemistry is known to be linked to that of copper in biological systems. Still, Cu+ /2+ is an essential micronutrient in many organisms, while no known biological process requires silver. In human cells, copper regulation and trafficking is strictly controlled by complex systems including many cytosolic copper chaperones, whereas some bacteria exploit the so-called "blue copper" proteins. Therefore, evaluating the controlling factors of the competition between these two metal cations is of enormous interest...

BACKGROUND: Hepatocellular carcinoma (HCC), one of the most common cancers worldwide, exhibits high immune heterogeneity and mortality. Emerging studies suggest that copper (Cu) plays a key role in cell survival. However, the relationship between Cu and tumor development remains unclear. METHODS: We investigated the effects of Cu and cuproptosis-related genes (CRGs) in patients with HCC in the TCGA-LIHC (The Cancer Genome Atlas-Liver cancer, n = 347) and ICGC-LIRI-JP (International Cancer Genome Consortium-Liver Cancer-Riken-Japan, n = 203) datasets...

Twenty-four dogs with OS underwent limb amputation. Serum, OS tumour, and normal bone were harvested at time of surgery. RNA was extracted and gene expression was performed using quantitative polymerase chain reaction (qPCR). Tissue and blood copper concentrations were also determined with spectrophotometry. Compared to bone, tumour samples had significantly higher expressions of antioxidant 1 copper chaperone (ATOX1, p = .0003). OS tumour copper levels were significantly higher than that of serum (p < ...

Copper is an essential trace element for living cells. However, copper can be potentially toxic for bacterial cells when it is present in excess amounts due to its redox potential. Due to its biocidal properties, copper is prevalent in marine systems due to its use in antifouling paints and as an algaecide. Thus, marine bacteria must possess means of sensing and responding to both high copper levels and those in which it is present at only typical trace metal levels. Bacteria harbor diverse regulatory mechanisms that respond to intracellular and extracellular copper and maintain copper homeostasis in cells...

Copper (Cu) was recently demonstrated to play a critical role in cellular physiological and biochemical processes, including energy production and maintenance, antioxidation and enzymatic activity, and signal transduction. Antioxidant 1 (ATOX1), a chaperone of Cu previously named human ATX1 homologue (HAH1), has been found to play an indispensable role in maintaining cellular Cu homeostasis, antioxidative stress, and transcriptional regulation. In the past decade, it has also been found to be involved in a variety of diseases, including numerous neurodegenerative diseases, cancers, and metabolic diseases...

Copper is an essential micronutrient but is toxic at high concentrations. In Haemophilus influenzae mechanisms of copper resistance and its role in pathogenesis are unknown; however, our previous genetic screen by transposon insertion-site sequencing implicated a putative cation transporting ATPase ( copA ) in survival in a mouse lung infection model. Here, we demonstrate that H. influenzae copA (HI0290) is responsible for copper homeostasis involving the merR -type regulator, cueR , as well as six tandem copies of the metallochaperone gene, copZ ...

Copper Chaperone For Superoxide Dismutase (CCS) genes encode copper chaperone for Superoxide dismutase (SOD) and dramatically affect the activity of SOD through regulating copper delivery from target to SOD. SOD is the effective component of the antioxidant defense system in plant cells to reduce oxidative damage by eliminating Reactive oxygen species (ROS), which are produced during abiotic stress. CCS might play an important role in abiotic stress to eliminate the damage caused by ROS, however, little is known about CCS in soybean in abiotic stress regulation...

BACKGROUND: Solute Carrier Family 31 Member 1 (SLC31A1) has recently been identified as a cuproptosis-regulatory gene. Recent studies have indicated that SLC31A1 may play a role in colorectal and lung cancer tumorigenesis. However, the role of SLC31A1 and its cuproptosis-regulatory functions in multiple tumor types remains to be further elucidated. METHODS: Online websites and datasets such as HPA, TIMER2, GEPIA, OncoVar, and cProSite were used to extract data on SLC31A1 in multiple cancers...

The filamentous fungus Aspergillus oryzae , in which sexual reproduction remains to be discovered, proliferates mainly via asexual spores (conidia). Therefore, despite its industrial importance in food fermentation and recombinant protein production, breeding beneficial strains by genetic crosses is difficult. In Aspergillus flavus , which is genetically close to A . oryzae , structures known as sclerotia are formed asexually, but they are also related to sexual development. Sclerotia are observed in some A ...