The molecular mechanisms of copper metabolism and its roles in human diseases

Chen, Ji; Jiang, Yunhui; Shi, Hua; Peng, Yougong; Fan, Xueying; Li, Chenghua

doi:10.1007/s00424-020-02412-2

Cited by 274 publications

(178 citation statements)

References 164 publications

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“…It is an important chemical component of cell biology because it can receive and donate electrons. Once delivered and spread in a body, the cycle of Cu ions as the cupric ion (Cu 2+ ) in its higher oxidation state and cuprous (reduced) form (Cu + ), often joined to cuproenzymes with a small proportion as labile Cu, which was named as free or unbound Cu [ 99 ]. As a redox catalyst, Cu is necessary for many enzymes’ catalytic activity, regulating various cellular, biochemical, and regulatory processes.…”

Section: Copper Ion Implication In Admentioning

confidence: 99%

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Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

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Alzheimer’s disease (AD) is an irreversible, age-related progressive neurological disorder, and the most common type of dementia in aged people. Neuropathological lesions of AD are neurofibrillary tangles (NFTs), and senile plaques comprise the accumulated amyloid-beta (Aβ), loaded with metal ions including Cu, Fe, or Zn. Some reports have identified metal dyshomeostasis as a neurotoxic factor of AD, among which Cu ions seem to be a central cationic metal in the formation of plaque and soluble oligomers, and have an essential role in the AD pathology. Cu-Aβ complex catalyzes the generation of reactive oxygen species (ROS) and results in oxidative damage. Several studies have indicated that oxidative stress plays a crucial role in the pathogenesis of AD. The connection of copper levels in AD is still ambiguous, as some researches indicate a Cu deficiency, while others show its higher content in AD, and therefore there is a need to increase and decrease its levels in animal models, respectively, to study which one is the cause. For more than twenty years, many in vitro studies have been devoted to identifying metals’ roles in Aβ accumulation, oxidative damage, and neurotoxicity. Towards the end, a short review of the modern therapeutic approach in chelation therapy, with the main focus on Cu ions, is discussed. Despite the lack of strong proofs of clinical advantage so far, the conjecture that using a therapeutic metal chelator is an effective strategy for AD remains popular. However, some recent reports of genetic-regulating copper transporters in AD models have shed light on treating this refractory disease. This review aims to succinctly present a better understanding of Cu ions’ current status in several AD features, and some conflicting reports are present herein.

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Section: Copper Ion Implication In Admentioning

confidence: 99%

“…So, a higher level of free Cu ions causes more toxicity to the cells and eventually leads to cell death. Therefore, cellular Cu should be tightly controlled ( Figure 3 ) [ 99 ].…”

Section: Copper Ion Implication In Admentioning

confidence: 99%

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Ejaz

Wang

Lang

2020

IJMS

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“…Our research focuses on the use of small quinoline molecules as metal ion chelators and potential anticancer agents [ 16 , 17 ]. The presence of copper ions is important in many biological processes and is essential for cellular physiology [ 18 ]. Copper is a co-factor of many enzymes and takes part in a variety of cellular processes in mammals [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

“…The presence of copper ions is important in many biological processes and is essential for cellular physiology [ 18 ]. Copper is a co-factor of many enzymes and takes part in a variety of cellular processes in mammals [ 18 ]. Changes in the homeostasis of copper ions play an important role in different types of diseases, such as inflammation, neurodegeneration, as well as in carcinogenesis (copper is an essential cofactor for cancer growth and angiogenesis) [ 18 , 19 , 20 , 21 ].…”

Section: Introductionmentioning

confidence: 99%

“…Copper is a co-factor of many enzymes and takes part in a variety of cellular processes in mammals [ 18 ]. Changes in the homeostasis of copper ions play an important role in different types of diseases, such as inflammation, neurodegeneration, as well as in carcinogenesis (copper is an essential cofactor for cancer growth and angiogenesis) [ 18 , 19 , 20 , 21 ]. Therefore, the use of metal chelating agents seems to be an ideal way to control the level of copper in the organism [ 21 , 22 , 23 ].…”

Section: Introductionmentioning

confidence: 99%

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8-Hydroxyquinoline Glycoconjugates Containing Sulfur at the Sugar Anomeric Position—Synthesis and Preliminary Evaluation of Their Cytotoxicity

et al. 2020

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One of the main factors limiting the effectiveness of many drugs is the difficulty of their delivery to their target site in the cell and achieving the desired therapeutic dose. Moreover, the accumulation of the drug in healthy tissue can lead to serious side effects. The way to improve the selectivity of a drug to the cancer cells seems to be its conjugation with a sugar molecule, which should facilitate its selective transport through GLUT transporters (glucose transporters), whose overexpression is seen in some types of cancer. This was the idea behind the synthesis of 8-hydroxyquinoline (8-HQ) derivative glycoconjugates, for which 1-thiosugar derivatives were used as sugar moiety donors. It was expected that the introduction of a sulfur atom instead of an oxygen atom into the anomeric position of the sugar would increase the stability of the obtained glycoconjugates against untimely hydrolytic cleavage. The anticancer activity of new compounds was determined based on the results of the MTT cytotoxicity tests. Because of the assumption that the activity of this type of compounds was based on metal ion chelation, the effect of the addition of copper ions on cell proliferation was tested for some of them. It turned out that cancer cells treated with glycoconjugates in the presence of Cu2+ had a much slower growth rate compared to cells treated with free glycoconjugates in the absence of copper. The highest cytotoxic activity of the compounds was observed against the MCF-7 cell line.

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Serum trace element levels and activity of enzymes associated with oxidative stress in endometriosis and endometrial cancer

Rabajdová,

Špaková,

Smolko

et al. 2023

FEBS Open Bio

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Abstract:Endometriosis and endometrial cancer are closely related with oxidative stress. However, the direct relationship between copper and zinc levels and oxidative stress in the extracellular and intracellular space remains unclear. The presented study is focused on determination of serum Zn and Cu levels, glutathione concentration and enzyme activity in three groups: patients diagnosed with endometrial cancer (EC), patients diagnosed with endometriosis (EM) and a healthy control group. Spectrophotometric determination of trace elements revealed that levels of zinc and copper were lower in blood plasma of patients with endometriosis as compared with the other groups; however, there were no significant differences in the Cu/Zn ratio. Furthermore, significantly increased blood serum glutathione levels were detected in both EM and EC groups compared to the control group. While the activity of superoxide dismutase (SOD) was similar across the studied groups, we observed differences in the activity of other enzymes associated with oxidative stress, including glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione S‐transferase (GST), between the control group and the EM and EC patients. Additionally, analysis of gene expression based on free circulating mRNA indicated significant differences in the expression of SOD isoenzymes between the patient groups and the control group; expression of GPx isoenzymes was also altered. Our results may have potential application in diagnostics as well as monitoring of endometriosis and endometrial cancer.

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The molecular mechanisms of copper metabolism and its roles in human diseases

Cited by 274 publications

References 164 publications

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

Copper Toxicity Links to Pathogenesis of Alzheimer’s Disease and Therapeutics Approaches

8-Hydroxyquinoline Glycoconjugates Containing Sulfur at the Sugar Anomeric Position—Synthesis and Preliminary Evaluation of Their Cytotoxicity

Serum trace element levels and activity of enzymes associated with oxidative stress in endometriosis and endometrial cancer

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