Toxicological mechanism of large amount of copper supplementation: Effects on endoplasmic reticulum stress and mitochondria-mediated apoptosis by Nrf2/HO-1 pathway-induced oxidative stress in the porcine myocardium

Li, Quanwei; Liao, Jianzhao; Zhang, Kai; Hu, Zhuoying; Zhang, Hui; Han, Qing; Guo, Jianying; Hu, Lianmei; Pan, Jiang; Liu, Ying; Li, Yuelong; Tang, Zhaoxin

doi:10.1016/j.jinorgbio.2022.111750

Cited by 21 publications

(2 citation statements)

References 45 publications

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“…Secondary antibodies were added and incubated for 1 h, and diaminobenzidine (DAB) was used for chromogenic development (Beyotime Biotechnology, China) and hematoxylin staining. Images were recorded under a microscope (Leica, Germany) …”

Section: Methodsmentioning

confidence: 99%

Drp1 Aggravates Copper Nanoparticle-Induced ER-Phagy by Disturbing Mitochondria-Associated Membranes in Chicken Hepatocytes

Li,

Guo,

Wang

et al. 2024

J. Agric. Food Chem.

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As an efficient alternative copper (Cu) source, copper nanoparticles (nano-Cu) have been widely supplemented into animal-producing food. Therefore, it is necessary to assess the effect of nano-Cu exposure on the biological health risk. Recently, the toxic effects of nano-Cu have been confirmed but the underlying mechanism remains unclear. This study reveals the impact of nano-Cu on endoplasmic reticulum autophagy (ER-phagy) in chicken hepatocytes and further identifies Drp1 and its downstream gene FAM134B as crucial regulators of nano-Cu-induced hepatotoxicity. Nano-Cu exposure can induce Cu ion overaccumulation and pathological injury in the liver, trigger excessive mitochondrial fission and mitochondria-associated membrane (MAM) integrity damage, and activate ER-phagy in vivo and in vitro. Interestingly, the knockdown of Drp1 markedly decreases the expression of FAM134B induced by nano-Cu. Furthermore, the expression levels of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I induced by nano-Cu exposure are decreased by inhibiting the expression of Drp1. Simultaneously, the inhibition of FAM134B effectively alleviates nano-Cu-induced ER-phagy by downregulating the expression of ATL3, CCPG1, SEC62, TEX264, and LC3II/LC3I. Overall, these results suggest that Drp1-mediated impairment of MAM integrity leads to ER-phagy as a novel molecular mechanism involved in the regulation of nano-Cu-induced hepatotoxicity. These findings provide new ideas for future research on the mechanism of nano-Cu-induced hepatotoxicity.

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Section: Methodsmentioning

confidence: 99%

Drp1 Aggravates Copper Nanoparticle-Induced ER-Phagy by Disturbing Mitochondria-Associated Membranes in Chicken Hepatocytes

Li,

Guo,

Wang

et al. 2024

J. Agric. Food Chem.

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“…The signaling pathways associated with copper-induced oxidative stress have been explored mainly based on in vitro cell experiments and in vivo animal studies. These studies demonstrated that a large amount of copper intake can result in oxidative damage by activating the antioxidant protection signals mitogen-activated protein kinase 14 (MAPK14)/the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1)/NAD(P)H:quinone oxidoreductase 1 (NQO1) pathway, inhibiting cAMP-response element binding protein (CREB)/Brain-derived neurotrophic factor (BDNF) pathway or PI3K/AKT/mTOR pathway to induce apoptosis or autophagy (Figure 2; Filomeni et al, 2011;Boilan et al, 2013;Zhong et al, 2014;Xie et al, 2020;Zou et al, 2021;Li et al, 2022;Lu et al, 2022;Zhong et al, 2022) degradation of mitochondria by phosphorylating the ser-73 and ser-254 residues of Sestrin 2 under copper-induced oxidative stress conditions (Kim et al, 2020). In addition, copper can destroy the antioxidant defense system by decreasing antioxidant enzyme activities (SOD, CAT, and GSH-Px) to induce toxicity (Lai et al, 1996;West and Prohaska, 2004;Sun et al, 2018;Jian et al, 2020).…”

Section: The Role Of Copper In Oxidative Stress and Inflammationmentioning

confidence: 99%

The emerging role of copper in depression

2023

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Copper (Cu) is an essential trace element in the brain and serves as an important cofactor for numerous enzymes involved in a wide range of biochemical processes including neurobehavioral, mitochondrial respiration, and antioxidant effects. Recent studies have demonstrated that copper dyshomeostasis is tightly associated with the development of depression by inducing oxidative stress and inflammatory responses. However, these findings have remained controversial so far. Cumulative studies have shown a positive association, while some other studies showed no association and even a negative association between serum/plasma copper level and depression. Based on these conflicted results, the association was speculated to be due to the clinical features of the population, stages of the disease, severity of copper excess, and types of specimens detected in these studies. In addition, there was an inverse association between dietary copper intake and depression. Furthermore, increasing copper intake could influence dietary zinc and iron intake to prevent and treat depression. Thus, copper supplementation may be a good measure to manage depression. This review provided a deeper understanding of the potential applicability of copper in the prevention and treatment of depression.

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Copper‐loaded Milk‐Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction

Hong,

Tian,

Dai

et al. 2024

Advanced Science

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Myocardial Infarction (MI) is a leading cause of death worldwide. Metabolic modulation is a promising therapeutic approach to prevent adverse remodeling after MI. However, whether material‐derived cues can treat MI through metabolic regulation is mainly unexplored. Herein, a Cu2+ loaded casein microgel (CuCMG) aiming to rescue the pathological intramyocardial metabolism for MI amelioration is developed. Cu2+ is an important ion factor involved in metabolic pathways, and intracardiac copper drain is observed after MI. It is thus speculated that intramyocardial supplementation of Cu2+ can rescue myocardial metabolism. Casein, a milk‐derived protein, is screened out as Cu2+ carrier through molecular‐docking based on Cu2+ loading capacity and accessibility. CuCMGs notably attenuate MI‐induced cardiac dysfunction and maladaptive remodeling, accompanied by increased angiogenesis. The results from unbiased transcriptome profiling and oxidative phosphorylation analyses support the hypothesis that CuCMG prominently rescued the metabolic homeostasis of myocardium after MI. These findings enhance the understanding of the design and application of metabolic‐modulating biomaterials for ischemic cardiomyopathy therapy.

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Toxicological mechanism of large amount of copper supplementation: Effects on endoplasmic reticulum stress and mitochondria-mediated apoptosis by Nrf2/HO-1 pathway-induced oxidative stress in the porcine myocardium

Cited by 21 publications

References 45 publications

Drp1 Aggravates Copper Nanoparticle-Induced ER-Phagy by Disturbing Mitochondria-Associated Membranes in Chicken Hepatocytes

Drp1 Aggravates Copper Nanoparticle-Induced ER-Phagy by Disturbing Mitochondria-Associated Membranes in Chicken Hepatocytes

The emerging role of copper in depression

Copper‐loaded Milk‐Protein Derived Microgel Preserves Cardiac Metabolic Homeostasis After Myocardial Infarction

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