Preview

Acta Biomedica Scientifica

Advanced search

The effect of copper acetate on hepatocyte metabolism in vitro

https://doi.org/10.29413/ABS.2024-9.6.2

Abstract

Background. Copper ions are necessary for maintaining basic physiological processes in the mammalian organism. However, their excessive absorption or accumulation in cells can lead to the development or exacerbation of various pathological processes. The  cytotoxic and  genotoxic effects of  high concentrations of  copper compounds are  currently well studied in  various cell cultures, whereas the  effect of non-toxic amounts of copper ions on physiological processes in cells, including during their cultivation, has been extremely poorly studied.

The aim of the study. To investigate the effect of copper ions on changes in the intracellular amount of mitochondrial cytochrome C oxidase and glutathione synthetase.

Materials and methods. A primary culture of hepatocytes was obtained, which was exposed to copper acetate at a concentration of 200 µg/ml in terms of copper content for 24 hours. After fixation, the samples were stained immunocytochemically using antibodies to  cytochrome  C oxidase (CcO) subunit  I and  glutathione synthetase (GS).

Results. In  hepatocyte culture, a  significant increase in  the  intensity of  fluorescent staining of the two analyzed enzymes was demonstrated both after 6 hours and  after  24  hours of  exposure to  copper ions, which indicates a  change in  their number in  cells. At  the  same time, the  increase in  the  amount of  CcO was more intense in the first 6 hours of incubation with a microelement, whereas in the next 18 hours, changes in the intracellular content of CcO were less pronounced. The increase in the intensity of the GS fluorescent stain was more active and was observed throughout the entire cultivation period.

Conclusion. From the  results obtained, it  can  be concluded that copper ions in  non-toxic concentrations are  able to  influence key indicators of  cell viability in culture by changing the amount of one of the main energy metabolism enzymes and the enzyme that provides synthesis of the most important low-molecular antioxidant glutathione.

About the Authors

I. S. Trukhan
Irkutsk Scientific Centre of Surgery and Traumatology
Russian Federation

Irina  S. Trukhan – Cand.  Sc. (Biol.), Senior Research Officer at  the  Laboratory of  Cell Technologies and Regenerative Medicine,

Bortsov Revolyutsii str. 1, Irkutsk 664003



N. N. Dremina
Irkutsk Scientific Centre of Surgery and Traumatology
Russian Federation

Natalya N. Dremina – Cand. Sc. (Biol.), Senior Research Officer at the Laboratory of Cell Technologies and Regenerative Medicine,

Bortsov Revolyutsii str. 1, Irkutsk 664003



I. A. Shurygina
Irkutsk Scientific Centre of Surgery and Traumatology
Russian Federation

Irina A. Shurygina – Dr. Sc. (Med.), Professor of the RAS, Deputy Director for Science, 

Bortsov Revolyutsii str. 1, Irkutsk 664003



References

1. Rahimzadeh MR, Kazemi S, Moghadamnia AA. Copper poisoning with emphasis on its clinical manifestations and treatment of intoxication. Adv Public Health. 2024; 6001014. doi: 10.1155/2024/60010142

2. Xue Q, Kang R, Klionsky DJ, Tang D, Liu J, Chen X. Copper metabolism in cell death and autophagy. Autophagy. 2023; 19(8): 2175-2195. doi: 10.1080/15548627.2023.2200554

3. Sailer J, Nagel J, Akdogan B, Jauch AT, Engler J, Knolle PA, et al. Deadly excess copper. Redox Biol. 2024; 75: 103256. doi: 10.1016/j.redox.2024.103256

4. Wungjiranirun M, Sharzehi K. Wilson’s disease. Semin Neurol. 2023; 43(4): 626-633. doi: 10.1055/s-0043-1771465

5. Saporito-Magriñá CM, Musacco-Sebio RN, Andrieux G, Kook L, Orrego MT, Tuttolomondo MV, et al. Copper-induced cell death and the protective role of glutathione: The implication of impaired protein folding rather than oxidative stress. Metallomics. 2018; 10(12): 1743-1754. doi: 10.1039/c8mt00182k

6. Ruiz LM, Libedinsky A, Elorza AA. Role of copper on mitochondrial function and metabolism. Front Mol Biosci. 2021; 8: 711227. doi: 10.3389/fmolb.2021.711227

7. Oe S, Miyagawa K, Honma Y, Harada M. Copper induces hepatocyte injury due to the endoplasmic reticulum stress in cultured cells and patients with Wilson disease. Exp Cell Res. 2016; 347(1): 192-200. doi: 10.1016/j.yexcr.2016.08.003

8. Husain N, Mahmood R. Copper (II) generates ROS and RNS, impairs antioxidant system and damages membrane and DNA in human blood cells. Environ Sci Pollut Res Int. 2019; 26(20): 20654- 20668. doi: 10.1007/s11356-019-05345-1

9. Yang F, Pei R, Zhang Z, Liao J, Yu W, Qiao N, et al Copper induces oxidative stress and apoptosis through mitochondriamediated pathway in chicken hepatocytes. Toxicol In Vitro. 2019; 54: 310-316. doi: 10.1016/j.tiv.2018.10.017

10. Kang Z, Qiao N, Liu G, Chen H, Tang Z, Li Y. Copper-induced apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction in male germ cells. Toxicol In Vitro. 2019; 61: 104639. doi: 10.1016/j.tiv.2019.104639

11. Wang X, Cao H, Fang Y, Bai H, Chen J, Xing C, et al. Activation of endoplasmic reticulum-mitochondria coupling drives copper-induced autophagy in duck renal tubular epithelial cells. Ecotoxicol Environ Saf. 2022; 235: 113438. doi: 10.1016/j.ecoenv.2022.113438

12. Yang F, Liao J, Yu W, Qiao N, Guo J, Han Q, et al. Exposure to copper induces mitochondria-mediated apoptosis by inhibiting mitophagy and the PINK1/parkin pathway in chicken (Gallus gallus) livers. J Hazard Mater. 2021; 408: 124888. doi: 10.1016/j.jhazmat.2020.124888

13. Zhang C, Huang T, Li L. Targeting cuproptosis for cancer therapy: Mechanistic insights and clinical perspectives. J Hematol Oncol. 2024; 17(1): 68. doi: 10.1186/s13045-024-01589-8

14. Kong R, Sun G. Targeting copper metabolism: A promising strategy for cancer treatment. Front Pharmacol. 2023; 14: 1203447. doi: 10.3389/fphar.2023.1203447

15. Dremina NN, Trukhan IS, Say OV, Shurygina IA. Activity of hepatic enzymes of isolated hepatocytes under the influence of copper acetate. International Journal of Biomedicine. 2022; 12(1): 58-62. doi: 10.21103/Article12(1)_OA8

16. Shurygina IA, Trukhan IS, Dremina NN, Say OV, Shurygin MG, Prozorova GF, et al. Evaluation of the safety and toxicity of the original copper nanocomposite based on poly-N-vinylimidazole. Nanomaterials (Basel). 2021; 12(1): 16. doi: 10.3390/nano12010016

17. Chicherin IV, Dashinimaev E, Baleva M, Krasheninnikov I, Levitskii S, Kamenski P. Cytochrome C oxidase on the crossroads of transcriptional regulation and bioenergetics. Front Physiol. 2019; 10: 644. doi: 10.3389/fphys.2019.00644

18. Timón-Gómez A, Nývltová E, Abriata LA, Vila AJ, Hosler J, Barrientos A. Mitochondrial cytochrome C oxidase biogenesis: Recent developments. Semin Cell Dev Biol. 2018; 76: 163-178. doi: 10.1016/j.semcdb.2017.08.055

19. Chen TH, Wang HC, Chang CJ, Lee SY. Mitochondrial glutathione in cellular redox homeostasis and disease manifestation. Int J Mol Sci. 2024; 25(2): 1314. doi: 10.3390/ijms25021314

20. Lu SC. Regulation of glutathione synthesis. Mol Aspects Med. 2009; 30(1-2): 42-59. doi: 10.1016/j.mam.2008.05.005

21. Egbujor MC, Olaniyan OT, Emeruwa CN, Saha S, Saso L, Tucci P. An insight into role of amino acids as antioxidants via NRF2 activation. Amino Acids. 2024; 56(1): 23. doi: 10.1007/s00726-024-03384-8

22. Zeng H, Saari JT, Johnson WT. Copper deficiency decreases complex IV but not complex I, II, III, or V in the mitochondrial respiratory chain in rat heart. JNutr. 2007; 137(1): 14-18. doi: 10.1093/jn/137.1.14

23. Johnson WT, Brown-Borg HM. Cardiac cytochrome C oxidase deficiency occurs during late postnatal development in progeny of copper-deficient rats. Exp Biol Med (Maywood). 2006; 231(2): 172-180. doi: 10.1177/153537020623100207

24. Ruiz LM, Jensen EL, Rossel Y, Puas GI, GonzalezIbanez AM, Bustos RI, et al. Non-cytotoxic copper overload boosts mitochondrial energy metabolism to modulate cell proliferation and differentiation in the human erythroleukemic cell line K562. Mitochondrion. 2016; 29: 18-30. doi: 10.1016/j.mito.2016.04.005

25. Dhar SS, Johar K, Wong-Riley MT. Bigenomic transcriptional regulation of all thirteen cytochrome C oxidase subunit genes by specificity protein 1. Open Biol. 2013; 3(3): 120176. doi: 10.1098/rsob.120176

26. Song MO, Mattie MD, Lee CH, Freedman JH. The role of Nrf1 and Nrf2 in the regulation of copper-responsive transcription. Exp Cell Res. 2014; 322(1): 39-50. doi: 10.1016/j.yexcr.2014.01.013

27. Bouda E, Stapon A, Garcia-Diaz M. Mechanisms of mammalian mitochondrial transcription. Protein Sci. 2019; 28(9): 1594- 1605. doi: 10.1002/pro.3688

28. Xia JL, Wu S, Zhang RY, Zhang CG, He H, Jiang HC, et al. Effects of copper exposure on expression of glutathione-related genes in Acidithiobacillus ferrooxidans. Curr Microbiol. 2011; 62(5): 1460-1466. doi: 10.1007/s00284-011-9881-9

29. Tillquist NM, Thorndyke MP, Thomas TA, Coleman SJ, Engle TE. Impact of cell culture and copper dose on gene expression in bovine liver. Biol Trace Elem Res. 2022; 200(5): 2113-2121. doi: 10.1007/s12011-021-02829-5

30. Mattie MD, Freedman JH. Copper-inducible transcription: Regulation by metal- and oxidative stress-responsive pathways. Am J Physiol Cell Physiol. 2004; 286(2): C293-C301. doi: 10.1152/ajpcell.00293.2003

31. Samet JM, Graves LM, Quay J, Dailey LA, Devlin RB, Ghio AJ, et al. Activation of MAPKs in human bronchial epithelial cells exposed to metals. Am J Physiol Lung Cell Mol Physiol. 1998; 275(3): L551-L558. doi: 10.1152/ajplung.1998.275.3.L551


Review

For citations:


Trukhan I.S., Dremina N.N., Shurygina I.A. The effect of copper acetate on hepatocyte metabolism in vitro. Acta Biomedica Scientifica. 2024;9(6):12-21. (In Russ.) https://doi.org/10.29413/ABS.2024-9.6.2

Views: 283


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2541-9420 (Print)
ISSN 2587-9596 (Online)