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Influence of B16/F10 melanoma growth variant on calcium levels in mitochondria in various organs of female mice

https://doi.org/10.17709/2409-2231-2021-8-1-2

Abstract

Purpose of the study. To analyze the calcium levels in mitochondria of cells in different organs in standard and stimulated growth of experimental В16/F10 melanoma.
Materials and Methods. The study included female С57ВL/6 mice (n=168). Experimental groups: intact group (n=21), group with a model of chronic neurogenic pain (CNP) (n=21), group M – B16/F10 melanoma (n=63), group M+CNP – mice (n=63) with transplantation of B16/F10 melanoma 3 weeks after CNP model creation. The concentration of calcium in mitochondrial samples was determined by a biochemical method (Abris+, Russia). Results were statistically analyzed using the Statistica 10.0 program.
Results. CNP decreased calcium levels in mitochondria of cells in the brain by 1.4 (р=0.00153) times, liver by 2.6 times and heart by 3.2 times and increased the levels in the skin by 97.1 times. In standard growth of experimental melanoma, levels of calcium in cell mitochondria in most of the studied organs increased at the initial stage of the melanoma growth, and decreased to intact values and lower by the terminal stage. In the mitochondria of tumor cells, calcium levels were stably high at all stages of standard tumor growth. At the initial stage of CNP‑stimulated tumor growth, a decrease in calcium in the mitochondria of the skin by 5.7 times and its accumulation in the mitochondria of the brain by 6.6 times, heart, and kidneys were recorded by 1.5 times. At the terminal stage of stimulated melanoma growth, extremely low calcium values were recorded in the mitochondria of all organs. A stably low level of calcium was registered in the mitochondria of tumor cells at all stages of stimulated melanoma growth.
Conclusions. The growth of experimental B16/F10 melanoma in female mice is accompanied by mitochondrial dysfunction affecting most organs. Stimulation of the growth of experimental melanoma with chronic neurogenic pain, unlike the standard growth variant, changes accumulation of calcium in the mitochondria of cells both in organs and in the tumor itself. The chronic pain syndrome accompanying a malignant process can influence its course with the involvement of mitochondria and the modification of their functions.

About the Authors

O. I. Kit
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Oleg I. Kit – corresponding member of Russian Academy of Sciences, Dr. Sci. (Med.), professor, general director

SPIN: 1728-0329, Scopus AuthorID: 55994103100, ResearcherID: U-2241-2017

63 14 line str., Rostov-on-Don 344037



E. M. Frantsiyants
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Elena M. Frantsiyants – Dr. Sci. (Biol.), professor, deputy director general for science, head of the laboratory for the study of the pathogenesis of malignant tumors

AuthorID: 462868, Scopus AuthorID: 55890047700, ResearcherID: Y-1491-2018

63 14 line str., Rostov-on-Don 344037



I. V. Neskubina
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Irina V. Neskubina – Cand. Sci. (Biol.), senior researcher at the laboratory for the study of the pathogenesis of malignant tumors

SPIN: 3581-8531, AuthorID: 794688

63 14 line str., Rostov-on-Don 344037



E. I. Surikova
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Ekaterina I. Surikova – Cand. Sci. (Biol.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors

SPIN: 2401-4115, AuthorID: 301537

63 14 line str., Rostov-on-Don 344037



I. V. Kaplieva
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Irina V. Kaplieva – Dr. Sci. (Med.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors

SPIN: 5047-1541, AuthorID: 734116

63 14 line str., Rostov-on-Don 344037



V. A. Bandovkina
National Medical Research Centre for Oncology of the Ministry of Health of Russia
Russian Federation

Valeriya A. Bandovkina – Cand. Sci. (Biol.), senior researcher of the laboratory for the study of pathogenesis of malignant tumors

SPIN: 8806-2641, AuthorID: 696989

63 14 line str., Rostov-on-Don 344037



References

1. Bustos G, Cruz P, Lovy A, Cárdenas C. Endoplasmic Reticulum-Mitochondria Calcium Communication and the Regulation of Mitochondrial Metabolism in Cancer: A Novel Potential Target. Front Oncol. 2017;7:199. https://doi.org/10.3389/fonc.2017.00199

2. Paupe V, Prudent J. New insights into the role of mitochondrial calcium homeostasis in cell migration. Biochemical and biophysical research communications. 2018 May 27;500(1):75–86. https://doi.org/10.1016/j.bbrc.2017.05.039

3. Bonora M, Morganti C, Morciano G, Pedriali G, Lebiedzinska-Arciszewska M, Aquila G, et al. Mitochondrial permeability transition involves dissociation of F1FO ATP synthase dimers and C-ring conformation. EMBO Rep. 2017 Jul;18(7):1077–1089. https://doi.org/10.15252/embr.201643602

4. Morciano G, Marchi S, Morganti C, Sbano L, Bittremieux M, Kerkhofs M, et al. Role of Mitochondria-Associated ER Membranes in Calcium Regulation in Cancer-Specific Settings. Neoplasia. 2018 May;20(5):510–523. https://doi.org/10.1016/j.neo.2018.03.005

5. Wu W, Lin C, Wu K, Jiang L, Wang X, Li W, et al. FUNDC1 regulates mitochondrial dynamics at the ER-mitochondrial contact site under hypoxic conditions. EMBO J. 2016 Jul 1;35(13):1368–1384. https://doi.org/10.15252/embj.201593102

6. Yoboue ED, Rimessi A, Anelli T, Pinton P, Sitia R. Regulation of Calcium Fluxes by GPX8, a Type-II Transmembrane Peroxidase Enriched at the Mitochondria-Associated Endoplasmic Reticulum Membrane. Antioxid Redox Signal. 2017 Sep 20;27(9):583–595. https://doi.org/10.1089/ars.2016.6866

7. Rowland AA, Voeltz GK. Endoplasmic reticulum-mitochondria contacts: function of the junction. Nat Rev Mol Cell Biol. 2012 Oct;13(10):607–625. https://doi.org/10.1038/nrm3440

8. Wang X, Schwarz TL. The mechanism of Ca2+ -dependent regulation of kinesin-mediated mitochondrial motility. Cell. 2009 Jan 9;136(1):163–174. https://doi.org/10.1016/j.cell.2008.11.046

9. Booth DM, Enyedi B, Geiszt M, Várnai P, Hajnóczky G. Redox Nanodomains Are Induced by and Control Calcium Signaling at the ER-Mitochondrial Interface. Mol Cell. 2016 Jul 21;63(2):240–248. https://doi.org/10.1016/j.molcel.2016.05.040

10. Gutierrez T, Simmen T. Endoplasmic reticulum chaperones tweak the mitochondrial calcium rheostat to control metabolism and cell death. Cell Calcium. 2018 Mar;70:64–75. https://doi.org/10.1016/j.ceca.2017.05.015

11. Sassano ML, van Vliet AR, Agostinis P. Mitochondria-Associated Membranes As Networking Platforms and Regulators of Cancer Cell Fate. Front Oncol. 2017;7:174. https://doi.org/10.3389/fonc.2017.00174

12. Ivanova H, Kerkhofs M, La Rovere RM, Bultynck G. Endoplasmic Reticulum-Mitochondrial Ca2+ Fluxes Underlying Cancer Cell Survival. Front Oncol. 2017;7:70. https://doi.org/10.3389/fonc.2017.00070

13. Kit OI, Frantsiyants EM, Kotieva IM, Kaplieva IV, Trepitaki LK, Bandovkina VA, et al. Some mechanisms of increasing malignancy of B16/F10 melanoma in female mice with chronic pain. Russian Journal of Pain. 2017;2(53):14–20. (In Russian).

14. Egorova MV, Afanasiev SA. Isolation of mitochondria from cells and tissues of animals and human: modern methodical approaches. Siberian Medical Journal. 2011;26(1-1):22–28. (In Russian).

15. Umemoto T, Hashimoto M, Matsumura T, Nakamura-Ishizu A, Suda T. Ca2+-mitochondria axis drives cell division in hematopoietic stem cells. J Exp Med. 2018 Aug 6;215(8):2097–2113. https://doi.org/10.1084/jem.20180421

16. Favero G, Bonomini F, Franco C, Rezzani R. Mitochondrial Dysfunction in Skeletal Muscle of a Fibromyalgia Model: The Potential Benefits of Melatonin. Int J Mol Sci. 2019 Feb 11;20(3):765. https://doi.org/10.3390/ijms20030765

17. Da Silva MF, Natali AJ, da Silva E, Gomes GJ, Teodoro BG, Cunha DNQ, et al. Attenuation of Ca2+ homeostasis, oxidative stress, and mitochondrial dysfunctions in diabetic rat heart: insulin therapy or aerobic exercise? J Appl Physiol (1985). 2015 Jul 15;119(2):148–156. https://doi.org/10.1152/japplphysiol.00915.2014

18. Diaz-Juarez J, Suarez J, Cividini F, Scott BT, Diemer T, Dai A, et al. Expression of the mitochondrial calcium uniporter in cardiac myocytes improves impaired mitochondrial calcium handling and metabolism in simulated hyperglycemia. Am J Physiol Cell Physiol. 2016 Dec 1;311(6):C1005–1013. https://doi.org/10.1152/ajpcell.00236.2016

19. Belosludtsev KN, Dubinin MV, Belosludtseva NV, Mironova GD. Mitochondrial Ca2+Transport: Mechanisms, Molecular Structures, and Role in Cells. Biochemistry (Mosc). 2019 Jun;84(6):593–607. https://doi.org/10.1134/S0006297919060026

20. Briston T, Selwood DL, Szabadkai G, Duchen MR. Mitochondrial Permeability Transition: A Molecular Lesion with Multiple Drug Targets. Trends Pharmacol Sci. 2019 Jan;40(1):50– 70. https://doi.org/10.1016/j.tips.2018.11.004

21. Belosludtsev KN, Belosludtseva NV, Agafonov AV, Astashev ME, Kazakov AS, Saris N-EL, et al. Ca(2+)-dependent permeabilization of mitochondria and liposomes by palmitic and oleic acids: a comparative study. Biochim Biophys Acta. 2014 Oct;1838(10):2600–2606. https://doi.org/10.1016/j.bbamem.2014.06.017

22. Mironova GD, Saris N-EL, Belosludtseva NV, Agafonov AV, Elantsev AB, Belosludtsev KN. Involvement of palmitate/Ca2+(Sr2+)-induced pore in the cycling of ions across the mitochondrial membrane. Biochim Biophys Acta. 2015 Feb;1848(2):488–495. https://doi.org/10.1016/j.bbamem.2014.10.027

23. Paillard M, Csordás G, Szanda G, Golenár T, Debattisti V, Bartok A, et al. Tissue-Specific Mitochondrial Decoding of Cytoplasmic Ca2+ Signals Is Controlled by the Stoichiometry of MICU1/2 and MCU. Cell Rep. 2017 Mar 7;18(10):2291–2300. https://doi.org/10.1016/j.celrep.2017.02.032

24. Santulli G, Xie W, Reiken SR, Marks AR. Mitochondrial calcium overload is a key determinant in heart failure. Proc Natl Acad Sci U S A. 2015 Sep 8;112(36):11389–11394. https://doi.org/10.1073/pnas.1513047112


Review

For citations:


Kit O.I., Frantsiyants E.M., Neskubina I.V., Surikova E.I., Kaplieva I.V., Bandovkina V.A. Influence of B16/F10 melanoma growth variant on calcium levels in mitochondria in various organs of female mice. Research and Practical Medicine Journal. 2021;8(1):20-29. (In Russ.) https://doi.org/10.17709/2409-2231-2021-8-1-2

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