Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

Zhong, Chong-Chao; Zhao, Tao; Högstrand, Christer; Song, Chang-Chun; Zito, Ester; Tan, Xiao-Ying; Xu, Yi-Chuang; Song, Yong; Wei, Xiaolei; Luo, Zhi

doi:10.1016/j.bbadis.2023.166752

Cited by 10 publications

(2 citation statements)

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“…MTF1 can also regulate ATP7B expression by binding to the MRE of the ATP7B promoter (Stalke et al, 2020), which may help regulate the intracellular Cu balance. A recent study showed that Cu recruits MTF-1 to the MRE of the Nrf2 promoter and promotes Nrf2 overexpression (Zhong et al, 2023). In our study, the expression of NFE2L2 (Nrf2) and MTF1 was upregulated post-LTx, and NFE2L2 had a strong positive correlation with MTF1 (r = 0.5).…”

Section: Validation Of Biomarkers By Wb and Qrt-pcr In A Rat Lung Tra...supporting

confidence: 62%

Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

Qin,

Xiao,

et al. 2023

Front. Mol. Biosci.

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Background: Allograft lung ischemia-reperfusion injury (ALIRI) is a major cause of early primary graft dysfunction and poor long-term survival after lung transplantation (LTx); however, its pathogenesis has not been fully elucidated. Cell death is a mechanism underlying ALIRI. Cuproptosis is a recently discovered form of programmed cell death. To date, no studies have been conducted on the mechanisms by which cuproptosis-related genes (CRGs) regulate ALIRI. Therefore, we explored the potential biomarkers related to cuproptosis to provide new insights into the treatment of ALIRI.Materials and methods: Datasets containing pre- and post-LTx lung biopsy samples and CRGs were obtained from the GEO database and previous studies. We identified differentially expressed CRGs (DE-CRGs) and performed functional analyses. Biomarker genes were selected using three machine learning algorithms. The ROC curve and logistic regression model (LRM) of these biomarkers were constructed. CIBERSORT was used to calculate the number of infiltrating immune cells pre- and post-LTx, and the correlation between these biomarkers and immune cells was analyzed. A competing endogenous RNA network was constructed using these biomarkers. Finally, the biomarkers were verified in a validation set and a rat LTx model using qRT-PCR and Western blotting.Results: Fifteen DE-CRGs were identified. GO analysis revealed that DE-CRGs were significantly enriched in the mitochondrial acetyl-CoA biosynthetic process from pyruvate, protein lipoylation, the tricarboxylic acid (TCA) cycle, and copper-transporting ATPase activity. KEGG enrichment analysis showed that the DE-CRGs were mainly enriched in metabolic pathways, carbon metabolism, and the TCA cycle. NFE2L2, NLRP3, LIPT1, and MTF1 were identified as potential biomarker genes. The AUC of the ROC curve for each biomarker was greater than 0.8, and the LRM provided an excellent classifier with an AUC of 0.96. These biomarkers were validated in another dataset and a rat LTx model, which exhibited good performance. In the CIBERSORT analysis, differentially expressed immune cells were identified, and the biomarkers were associated with the immune cells.Conclusion:NFE2L2, NLRP3, LIPT1, and MTF1 may serve as predictors of cuproptosis and play an important role in the pathogenesis of cuproptosis in ALIRI.

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Section: Validation Of Biomarkers By Wb and Qrt-pcr In A Rat Lung Tra...supporting

confidence: 62%

Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

Qin,

Xiao,

et al. 2023

Front. Mol. Biosci.

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“…Cp is a protein containing copper that is secreted by hepatocytes, and hepatocyte-specific ablation of Cp reduces lipid accumulation, inhibits inflammation, attenuates fibrosis, and ameliorates liver injury, which may be associated with the remodeling of bile acid metabolism [228]. Furthermore, copper overload leads to lipogenesis, oxidative stress, and mitochondrial dysfunction, which induce hepatic steatosis and lipotoxicity [229,230]. Similarly, copper overload also mediates the programmed cell death known as cuproptosis, which is characterized by Cu + -mediated lipoacylation and the aggregation of enzymes that regulate the mitochondrial TCA cycle, particularly dihydrolipoamide S-acetyltransferase (DLAT), and loss of Fe-S clusters [231,232].…”

Section: Copper Metabolism and Mafldmentioning

confidence: 99%

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Fu,

Wang,

Qin

2024

Metabolites

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Metabolic-associated fatty liver disease (MAFLD), characterized primarily by hepatic steatosis, has become the most prevalent liver disease worldwide, affecting approximately two-fifths of the global population. The pathogenesis of MAFLD is extremely complex, and to date, there are no approved therapeutic drugs for clinical use. Considerable evidence indicates that various metabolic disorders play a pivotal role in the progression of MAFLD, including lipids, carbohydrates, amino acids, and micronutrients. In recent years, the medicinal properties of natural products have attracted widespread attention, and numerous studies have reported their efficacy in ameliorating metabolic disorders and subsequently alleviating MAFLD. This review aims to summarize the metabolic-associated pathological mechanisms of MAFLD, as well as the natural products that regulate metabolic pathways to alleviate MAFLD.

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Influences of dietary Cu levels on growth performance, muscle development, antioxidant capacity, and inflammatory response of juvenile yellow catfish (Pelteobagrus fulvidraco)

Xu,

Yang,

Wei

et al. 2024

Aquaculture Reports

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Copper induces liver lipotoxicity disease by up-regulating Nrf2 expression via the activation of MTF-1 and inhibition of SP1/Fyn pathway

Cited by 10 publications

References 56 publications

Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

Identification of cuproptosis-related biomarkers and analysis of immune infiltration in allograft lung ischemia-reperfusion injury

Examining the Pathogenesis of MAFLD and the Medicinal Properties of Natural Products from a Metabolic Perspective

Influences of dietary Cu levels on growth performance, muscle development, antioxidant capacity, and inflammatory response of juvenile yellow catfish (Pelteobagrus fulvidraco)

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