Association of copper metabolism disorder with cell damage and liver diseases

Corresponding author: GAO Yanhang， yanhang@mail.jlu.edu.cn （ORCID： 0000－0001－8590－6706）
Received Date: 2022-12-11
Accepted Date: 2023-01-29
Published Date: 2023-09-19

Abstract

Abstract

Copper is an essential trace element in human body and plays an important role in maintaining health in humans. Copper is involved in various metabolic pathways in human body， and copper metabolism disorder may lead to metabolic disorders such as impaired glucose tolerance and dyslipidemia. The liver plays a key role in maintaining copper homeostasis， and copper deficiency or excess may cause cell damage and liver dysfunction. Recent studies on copper metabolism have shown that copper metabolism disorder may result in cell damage by affecting oxidative stress， proteasome， cuproptosis， and angiogenesis and help to clarify the assumed mechanisms of liver diseases and metabolic disorders due to copper metabolism disorder. This article reviews the recent research advances in copper metabolism disorder in cell damage/death and chronic liver diseases， including Wilson’s disease， nonalcoholic fatty liver disease， and hepatocellular carcinoma， which helps to identify future research priorities.
- Liver Diseases,
- Cell Death,
- Copper Metabolism

FullText(HTML)

References(50)

References

[1]	TSVETKOV P, COY S, PETROVA B, et al. Copper induces cell death by targeting lipoylated TCA cycle proteins[J]. Science, 2022, 375( 6586): 1254－ 1261. DOI: 10.1126/science.abf0529.
[2]	DEV S, KRUSE RL, HAMILTON JP, et al. Wilson disease: update on pathophysiology and treatment[J]. Front Cell Dev Biol, 2022, 10: 871877. DOI: 10.3389/fcell.2022.871877.
[3]	HIMOTO T, MASAKI T. Current trends of essential trace elements in patients with chronic liver diseases[J]. Nutrients, 2020, 12( 7): 2084. DOI: 10.3390/nu12072084.
[4]	HUANG R, CHEN H, LIANG J, et al. Dual role of reactive oxygen species and their application in cancer therapy[J]. J Cancer, 2021, 12( 18): 5543－ 5561. DOI: 10.7150/jca.54699.
[5]	ROCHFORD G, MOLPHY Z, KAVANAGH K, et al. Cu(ii) phenanthroline－phenazine complexes dysregulate mitochondrial function and stimulate apoptosis[J]. Metallomics, 2020, 12( 1): 65－ 78. DOI: 10.1039/c9mt00187e.
[6]	HILTON JB, WHITE AR, CROUCH PJ. Metal－deficient SOD1 in amyotrophic lateral sclerosis[J]. J Mol Med(Berl), 2015, 93( 5): 481－ 487. DOI: 10.1007/s00109－015－1273－3.
[7]	GAŁCZYŃSKA K, DRULIS－KAWA Z, ARABSKI M. Antitumor activity of Pt(II), Ru(III) and Cu(II) complexes[J]. Molecules, 2020, 25( 15): 3492. DOI: 10.3390/molecules25153492.
[8]	SANTORO AM, MONACO I, ATTANASIO F, et al. Copper(II) ions affect the gating dynamics of the 20S proteasome: a molecular and in cell study[J]. Sci Rep, 2016, 6: 33444. DOI: 10.1038/srep33444.
[9]	TSVETKOV P, DETAPPE A, CAI K, et al. Mitochondrial metabolism promotes adaptation to proteotoxic stress[J]. Nat Chem Biol, 2019, 15( 7): 681－ 689. DOI: 10.1038/s41589－019－0291－9.
[10]	LI Y. Copper homeostasis: Emerging target for cancer treatment[J]. IUBMB Life, 2020, 72( 9): 1900－ 1908. DOI: 10.1002/iub.2341.
[11]	PARK KC, FOUANI L, JANSSON PJ, et al. Copper and conquer: copper complexes of di－2－pyridylketone thiosemicarbazones as novel anti－cancer therapeutics[J]. Metallomics, 2016, 8( 9): 874－ 886. DOI: 10.1039/c6mt00105j.
[12]	XU J, HUA X, YANG R, et al. XIAP interaction with E2F1 and Sp1 via its BIR2 and BIR3 domains specific activated MMP2 to promote bladder cancer invasion[J]. Oncogenesis, 2019, 8( 12): 71. DOI: 10.1038/s41389－019－0181－8.
[13]	KALITA J, KUMAR V, MISRA UK. A study on apoptosis and anti－apoptotic status in wilson disease[J]. Mol Neurobiol, 2016, 53( 10): 6659－ 6667. DOI: 10.1007/s12035－015－9570－y.
[14]	YANG F, LIAO J, PEI R, et al. Autophagy attenuates copper－induced mitochondrial dysfunction by regulating oxidative stress in chicken hepatocytes[J]. Chemosphere, 2018, 204: 36－ 43. DOI: 10.1016/j.chemosphere.2018.03.192.
[15]	HAZARI Y, BRAVO－SAN PEDRO JM, HETZ C, et al. Autophagy in hepatic adaptation to stress[J]. J Hepatol, 2020, 72( 1): 183－ 196. DOI: 10.1016/j.jhep.2019.08.026.
[16]	POLISHCHUK EV, MEROLLA A, LICHTMANNEGGER J, et al. Activation of autophagy, observed in liver tissues from patients with Wilson disease and from ATP7B－deficient animals, protects hepatocytes from copper－induced apoptosis[J]. Gastroenterology, 2019, 156( 4): 1173－ 1189. DOI: 10.1053/j.gastro.2018.11.032.
[17]	GAO W, HUANG Z, DUAN J, et al. Elesclomol induces copper－dependent ferroptosis in colorectal cancer cells via degradation of ATP7A[J]. Mol Oncol, 2021, 15( 12): 3527－ 3544. DOI: 10.1002/1878－0261.13079.
[18]	LI F, WU X, LIU H, et al. Copper depletion strongly enhances ferroptosis via mitochondrial perturbation and reduction in antioxidative mechanisms[J]. Antioxidants(Basel), 2022, 11( 11): 2084. DOI: 10.3390/antiox11112084.
[19]	GUO H, OUYANG Y, YIN H, et al. Induction of autophagy via the ROS－dependent AMPK－mTOR pathway protects copper－induced spermatogenesis disorder[J]. Redox Biol, 2022, 49: 102227. DOI: 10.1016/j.redox.2021.102227.
[20]	YANG M, WU X, HU J, et al. COMMD10 inhibits HIF1α/CP loop to enhance ferroptosis and radiosensitivity by disrupting Cu－Fe balance in hepatocellular carcinoma[J]. J Hepatol, 2022, 76( 5): 1138－ 1150. DOI: 10.1016/j.jhep.2022.01.009.
[21]	CHEN M, ZHENG J, LIU G, et al. Ceruloplasmin and hephaestin jointly protect the exocrine pancreas against oxidative damage by facilitating iron efflux[J]. Redox Biol, 2018, 17: 432－ 439. DOI: 10.1016/j.redox.2018.05.013.
[22]	ZISCHKA H, LICHTMANNEGGER J, SCHMITT S, et al. Liver mitochondrial membrane crosslinking and destruction in a rat model of Wilson disease[J]. J Clin Invest, 2011, 121( 4): 1508－ 1518. DOI: 10.1172/JCI45401.
[23]	HAMILTON JP, KOGANTI L, MUCHENDITSI A, et al. Activation of liver X receptor/retinoid X receptor pathway ameliorates liver disease in Atp7B(－/－‍)(Wilson disease) mice[J]. Hepatology, 2016, 63( 6): 1828－ 1841. DOI: 10.1002/hep.28406.
[24]	MEDICI V, SARODE GV, NAPOLI E, et al. mtDNA depletion－like syndrome in Wilson disease[J]. Liver Int, 2020, 40( 11): 2776－ 2787. DOI: 10.1111/liv.14646.
[25]	SHRIBMAN S, POUJOIS A, BANDMANN O, et al. Wilson’s disease: update on pathogenesis, biomarkers and treatments[J]. J Neurol Neurosurg Psychiatry, 2021, 92( 10): 1053－ 1061. DOI: 10.1136/jnnp－2021－326123.
[26]	PFEIFFENBERGER J, MOGLER C, GOTTHARDT DN, et al. Hepatobiliary malignancies in Wilson disease[J]. Liver Int, 2015, 35( 5): 1615－ 1622. DOI: 10.1111/liv.12727.
[27]	van MEER S, de MAN RA, van DEN BERG AP, et al. No increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long－term follow－up[J]. J Gastroenterol Hepatol, 2015, 30( 3): 535－ 539. DOI: 10.1111/jgh.12716.
[28]	YOUNOSSI Z, TACKE F, ARRESE M, et al. Global perspectives on nonalcoholic fatty liver disease and nonalcoholic steatohepatitis[J]. Hepatology, 2019, ‍ 69( 6): 2672－ 2682. DOI: 10.1002/hep.30251.
[29]	HEFFERN MC, PARK HM, AU－YEUNG HY, et al. In vivo bioluminescence imaging reveals copper deficiency in a murine model of nonalcoholic fatty liver disease[J]. Proc Natl Acad Sci U S A, 2016, 113( 50): 14219－ 14224. DOI: 10.1073/pnas.1613628113.
[30]	TOSCO A, FONTANELLA B, DANISE R, et al. Molecular bases of copper and iron deficiency－associated dyslipidemia: a microarray analysis of the rat intestinal transcriptome[J]. Genes Nutr, 2010, 5( 1): 1－ 8. DOI: 10.1007/s12263－009－0153－2.
[31]	SONG M, SCHUSCHKE DA, ZHOU Z, et al. High fructose feeding induces copper deficiency in Sprague－Dawley rats: a novel mechanism for obesity related fatty liver[J]. J Hepatol, 2012, 56( 2): 433－ 440. DOI: 10.1016/j.jhep.2011.05.030.
[32]	AIGNER E, THEURL I, HAUFE H, et al. Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease[J]. Gastroenterology, 2008, 135( 2): 680－ 688. DOI: 10.1053/j.gastro.2008.04.007.
[33]	TALLINO S, DUFFY M, RALLE M, et al. Nutrigenomics analysis reveals that copper deficiency and dietary sucrose up－regulate inflammation, fibrosis and lipogenic pathways in a mature rat model of nonalcoholic fatty liver disease[J]. J Nutr Biochem, 2015, 26( 10): 996－ 1006. DOI: 10.1016/j.jnutbio.2015.04.009.
[34]	BUZZETTI E, PARIKH PM, GERUSSI A, et al. Gender differences in liver disease and the drug－dose gender gap[J]. Pharmacol Res, 2017, 120: 97－ 108. DOI: 10.1016/j.phrs.2017.03.014.
[35]	LAN Y, WU S, WANG Y, et al. Association between blood copper and nonalcoholic fatty liver disease according to sex[J]. Clin Nutr, 2021, 40( 4): 2045－ 2052. DOI: 10.1016/j.clnu.2020.09.026.
[36]	STÄTTERMAYER AF, TRAUSSNIGG S, AIGNER E, et al. Low hepatic copper content and PNPLA3 polymorphism in non－alcoholic fatty liver disease in patients without metabolic syndrome[J]. J Trace Elem Med Biol, 2017, 39: 100－ 107. DOI: 10.1016/j.jtemb.2016.08.006.
[37]	EL－RAYAH EA, TWOMEY PJ, WALLACE EM, et al. Both α－1－antitrypsin Z phenotypes and low caeruloplasmin levels are over－represented in alcohol and nonalcoholic fatty liver disease cirrhotic patients undergoing liver transplant in Ireland[J]. Eur J Gastroenterol Hepatol, 2018, 30( 4): 364－ 367. DOI: 10.1097/MEG.0000000000001056.
[38]	YANG JD, HAINAUT P, GORES GJ, et al. A global view of hepatocellular carcinoma: trends, risk, prevention and management[J]. Nat Rev Gastroenterol Hepatol, 2019, 16( 10): 589－ 604. DOI: 10.1038/s41575－019－0186－y.
[39]	BALDARI S, DI ROCCO G, TOIETTA G. Current biomedical use of copper chelation therapy[J]. Int J Mol Sci, 2020, 21( 3): 1069. DOI: 10.3390/ijms21031069.
[40]	DAVIS CI, GU X, KIEFER RM, et al. Altered copper homeostasis underlies sensitivity of hepatocellular carcinoma to copper chelation[J]. Metallomics, 2020, 12( 12): 1995－ 2008. DOI: 10.1039/d0mt00156b.
[41]	PORCU C, ANTONUCCI L, BARBARO B, et al. Copper/MYC/CTR1 interplay: a dangerous relationship in hepatocellular carcinoma[J]. Oncotarget, 2018, 9( 10): 9325－ 9343. DOI: 10.18632/oncotarget.24282.
[42]	ZHU J, HUANG S, WU G, et al. Lysyl oxidase is predictive of unfavorable outcomes and essential for regulation of vascular endothelial growth factor in hepatocellular carcinoma[J]. Dig Dis Sci, 2015, 60( 10): 3019－ 3031. DOI: 10.1007/s10620－015－3734－5.
[43]	CHOI J, CHUNG T, RHEE H, et al. Increased expression of the matrix－modifying enzyme lysyl oxidase－like 2 in aggressive hepatocellular carcinoma with poor prognosis[J]. Gut Liver, 2019, 13( 1): 83－ 92. DOI: 10.5009/gnl17569.
[44]	MORISAWA A, OKUI T, SHIMO T, et al. Ammonium tetrathiomolybdate enhances the antitumor effects of cetuximab via the suppression of osteoclastogenesis in head and neck squamous carcinoma[J]. Int J Oncol, 2018, 52( 3): 989－ 999. DOI: 10.3892/ijo.2018.4242.
[45]	SINGLA A, CHEN Q, SUZUKI K, et al. Regulation of murine copper homeostasis by members of the COMMD protein family[J]. Dis Model Mech, 2021, 14( 1): dmm045963. DOI: 10.1242/dmm.045963.
[46]	YOSHII J, YOSHIJI H, KURIYAMA S, et al. The copper－chelating agent, trientine, suppresses tumor development and angiogenesis in the murine hepatocellular carcinoma cells[J]. Int J Cancer, 2001, 94( 6): 768－ 773. DOI: 10.1002/ijc.1537.
[47]	REZAEI A, MAHMOODI M, MOHAMMADIZADEH F, et al. A novel copper(II) complex activated both extrinsic and intrinsic apoptotic pathways in liver cancerous cells[J]. J Cell Biochem, 2019, 120( 8): 12280－ 12289. DOI: 10.1002/jcb.28491.
[48]	FANG AP, CHEN PY, WANG XY, et al. Serum copper and zinc levels at diagnosis and hepatocellular carcinoma survival in the Guangdong Liver Cancer Cohort[J]. Int J Cancer, 2019, 144( 11): 2823－ 2832. DOI: 10.1002/ijc.31991.
[49]	BAJ J, TERESIŃSKI G, FORMA A, et al. Chronic alcohol abuse alters hepatic trace element concentrations－metallomic study of hepatic elemental composition by means of ICP－OES[J]. Nutrients, 2022, 14( 3): 546. DOI: 10.3390/nu14030546.
[50]	ARAIN SA, KAZI TG, AFRIDI HI, et al. Estimation of copper and iron burden in biological samples of various stages of hepatitis C and liver cirrhosis patients[J]. Biol Trace Elem Res, 2014, 160( 2): 197－ 205. DOI: 10.1007/s12011－014－0058－9.

Relative Articles

[1]	Zhuoga RENZENG, Kangjie YANG, Yongliang LU, Zhixin WANG, Haijiu WANG. Research advances in neutrophil extracellular traps and liver diseases[J]. Journal of Clinical Hepatology, 2024, 40(3): 639-643. doi: 10.12449/JCH240334
[2]	Mingqiang ZHU, Xing XIE, Qicheng LIAO, Xiao HE, Youming DING, Xiaohua WANG. Mechanism of cuproptosis and its role in liver diseases[J]. Journal of Clinical Hepatology, 2024, 40(11): 2332-2337. doi: 10.12449/JCH241131
[3]	Guiqiang WANG. Application and prospect of cell therapy in clinical treatment of liver diseases[J]. Journal of Clinical Hepatology, 2023, 39(5): 1001-1003. doi: 10.3969/j.issn.1001-5256.2023.05.001
[4]	Zhuoran WANG, Bing ZHU, Limei YU, Shaoli YOU. Role of stem cell-derived exosomes in treatment of liver diseases[J]. Journal of Clinical Hepatology, 2023, 39(3): 699-706. doi: 10.3969/j.issn.1001-5256.2023.03.034
[5]	Feiyan LI, Minggang WANG, Dewen MAO, Xiongbin GUI. Role of gasdermin D in the pathological progression of liver diseases[J]. Journal of Clinical Hepatology, 2023, 39(3): 707-712. doi: 10.3969/j.issn.1001-5256.2023.03.035
[6]	Wenshang CHEN, Jijin ZHU, Shilai LI. Role of thymic stromal lymphopoietin in liver diseases[J]. Journal of Clinical Hepatology, 2022, 38(5): 1175-1178. doi: 10.3969/j.issn.1001-5256.2022.05.042
[7]	Weiyu CHEN, Faming SHU, Han WANG, Yanggang CAO, Jin HU, Dewen MAO. Role of the cytochrome P450 family in metabolic-associated liver diseases[J]. Journal of Clinical Hepatology, 2022, 38(9): 2182-2187. doi: 10.3969/j.issn.1001-5256.2022.09.045
[8]	Rui CHEN, Zhixin WANG, Haining FAN, Haijiu WANG. Research advances in the role of lymphocyte activation gene-3 in liver-related diseases[J]. Journal of Clinical Hepatology, 2021, 37(4): 977-981. doi: 10.3969/j.issn.1001-5256.2021.04.056
[9]	Lihui ZHANG, Minghao LIU, Wenxia ZHAO. Role of lipotoxicity in the development and progression of nonalcoholic fatty liver disease[J]. Journal of Clinical Hepatology, 2021, 37(2): 463-466. doi: 10.3969/j.issn.1001-5256.2021.02.045
[10]	Feiyu ZHANG, ADILA·Yakepu, Jinming ZHAO, Yanhang GAO. Mechanism of ferroptosis and its role in liver diseases[J]. Journal of Clinical Hepatology, 2021, 37(6): 1454-1458. doi: 10.3969/j.issn.1001-5256.2021.06.049
[11]	XU LiJun, AN XiuQin, LI Yue, LIU JinChun. Research advances in the role of myeloid-derived suppressor cells in liver diseases[J]. Journal of Clinical Hepatology, 2020, 36(12): 2851-2855. doi: 10.3969/j.issn.1001-5256.2020.12.045
[12]	XIAO WeiSong, LE YingYu, ZENG ShengLan, TAN XiaoBin, WU Cong, YA ChengYu, MAO DeWen. Role of pyroptosis in liver diseases[J]. Journal of Clinical Hepatology, 2020, 36(12): 2847-2850. doi: 10.3969/j.issn.1001-5256.2020.12.044
[13]	Wang ShaSha, Hua Fang, Jiao YongGeng, Qin ErYun, Zhi YiXiao, Pang MengYuan, Xu HongQin, Chi XiuMei, Niu JunQi, Hua Rui. Serum level of ceruloplasmin in patients with different liver diseases in Jilin,China[J]. Journal of Clinical Hepatology, 2020, 36(9): 2025-2029. doi: 10.3969/j.issn.1001-5256.2020.09.023
[14]	Chen ShuRu, Chong YuTian, Li XinHua. Pathogenic mechanism and clinical diagnosis of hereditary abnormal copper metabolism[J]. Journal of Clinical Hepatology, 2019, 35(8): 1667-1672. doi: 10.3969/j.issn.1001-5256.2019.08.003
[15]	Yu PengFei, Wu Qiao, Duan ZhongPing, Chen Yu. Research advances in the mechanism of drug-induced liver injury due to paracetamol[J]. Journal of Clinical Hepatology, 2019, 35(9): 2108-2112. doi: 10.3969/j.issn.1001-5256.2019.09.050
[16]	Chen Xiang, Wen DiGuang, You Yu, Gong JianPing. Role and mechanism of ferroptosis in treatment of liver cancer with sorafenib[J]. Journal of Clinical Hepatology, 2019, 35(10): 2316-2319. doi: 10.3969/j.issn.1001-5256.2019.10.040
[17]	Bao SuXia, Zheng JianMing, Shi GuangFeng. Research progress in association between interleukin-23 and liver diseases[J]. Journal of Clinical Hepatology, 2016, 32(2): 393-396. doi: 10.3969/j.issn.1001-5256.2016.02.044
[18]	Lu: XinPing, Wu Jing, Chen JingTao. Application of antibody preparation technology based on single B lymphocytes in liver diseases[J]. Journal of Clinical Hepatology, 2015, 31(12): 2104-2109. doi: 10.3969/j.issn.1001-5256.2015.12.028
[19]	Huang LanYu, Xu LieMing. Relationship between liver diseases and autophagy[J]. Journal of Clinical Hepatology, 2014, 30(2): 186-188. doi: 10.3969/j.issn.1001-5256.2014.02.022
[20]	Liu GuoWang, Cao WuKui. Application of stem cells in liver disease treatment[J]. Journal of Clinical Hepatology, 2011, 27(9): 999-1002.

Supplements(0)

Cited By

Cited by

Periodical cited type(4)

1.	郭新华，王佳慧，段雪琳，彭岳，赵铁建，郑洋，赵斌. 金属离子代谢：慢性肝病中医药防治新思路. 临床肝胆病杂志. 2024(07): 1498-1504 . 本站查看
2.	董昌君，张先林. 铜死亡在肝细胞癌发病机制中的研究进展. 中国普通外科杂志. 2024(07): 1172-1179 .
3.	刘诗卉，李冬冬，张宏坤，刘传苗，吴执竞，赵文. 细胞死亡在NAFLD发生发展中的研究进展. 齐齐哈尔医学院学报. 2024(16): 1578-1582 .
4.	朱明强，谢星，廖启成，何晓，丁佑铭，王小华. 铜死亡的发生机制及在肝脏疾病中的作用. 临床肝胆病杂志. 2024(11): 2332-2337 . 本站查看

Other cited types(1)

Proportional views

Proportional views

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Figures(2)

Get Citation

PDF

XML

Article Metrics

Article views (1132) PDF downloads(201)

Association of copper metabolism disorder with cell damage and liver diseases

DOI: 10.3969/j.issn.1001-5256.2023.09.032