The Effect of 20-Hydroxyecdysone on the Functioning of isolated Mouse Skeletal Muscle Mitochondria

A. A. Semenova; Семенова А. А.; A. D. Igoshkina; Игошкина А. Д.; N. V. Mikina; Микина Н. В.; R. G. Savchenko; Савченко Р. Г.; L. V. Parfenova; Парфенова Л. В.; M. V. Dubinin; Дубинин М. В.

doi:10.31857/S0233475524030067

The Effect of 20-Hydroxyecdysone on the Functioning of isolated Mouse Skeletal Muscle Mitochondria

Authors: Semenova A.A.¹, Igoshkina A.D.¹, Mikina N.V.¹, Savchenko R.G.², Parfenova L.V.², Dubinin M.V.¹
Affiliations:
1. Mari State University
2. Institute of Petrochemistry and Catalysis, Russian Academy of Sciences
Issue: Vol 41, No 3 (2024)
Pages: 233-242
Section: Articles
URL: https://journals.rcsi.science/0233-4755/article/view/260759
DOI: https://doi.org/10.31857/S0233475524030067
EDN: https://elibrary.ru/csbitx
ID: 260759

Cite item

Full Text

Open Access
Restricted Access

Access granted
Restricted Access

Subscription Access

Abstract
Full Text
About the authors
References
Supplementary files
Statistics

Abstract

This work shows the effect of the phytoecdysteroid 20-hydroxyecdysone (20E) on the functioning of mouse skeletal muscle mitochondria. I It has been shown that 20E at a concentration of 100 µM or more suppresses mitochondrial respiration fueled by glutamate and malate (substrates of complex I of the respiratory chain) or succinate (substrate of complex II of the respiratory chain). This effect of 20E is accompanied by a decrease in the membrane potential of organelles and is associated with inhibition of the activity of complex III, the total activity of complexes I+III and II+III of the mitochondrial respiratory chain. We have noted the prooxidant effect of 20E, which manifests itself in an increase in the production of hydrogen peroxide by skeletal muscle mitochondria. In addition, 20E reduces the ability of mitochondria to accumulate calcium ions in the matrix. The paper discusses the mechanisms of the possible toxic effect of 20E on the functioning of skeletal muscle mitochondria.

Keywords

mitochondria, 20-hydroxyecdysone, oxidative phosphorylation, respiratory chain, calcium, reactive oxygen species

Full Text

References

Koolman J. 1989. Ecdysone: From chemistry of mode of action. Stuttgart: Thieme Verlag, 482 p.
Toth N., Szabo A., Kacsala P., Heger J., Zador E. 2008. 20-Hydroxyecdysone increases fiber size in a muscle-specific fashion in rat. Phytomedicine. 15 (9), 691–698.
Lafont R., Harmatha J., Marion-Poll F., Dinan L., Wilson I.D. 2002. The ecdysone handbook. 3rd ed. Prague: Cybersales.
Savchenko R.G., Veskina N.A., Odinokov V.N., Benkovskaya G.V., Parfenova L.V. 2022. Ecdysteroids: Isolation, chemical transformations, and biological activity. Phytochem. Rev. 21, 1445–1486. doi: 10.1007/s11101-021-09792-y.
Bathori M., Toth N., Hunyadi A., Marki A., Zador E. 2008. Phytoecdysteroids and anabolic–androgenic steroids – structure and effects on humans. Curr. Med. Chem. 15, 75–91.
Slama K., Lafont R. 1995. Insect hormones – ecdysteroids: Their presence and actions in vertebrates. Eur. J. Entomol. 92, 355–377.
Dinan L., Lafont R. 2006. Effects and applications of arthropod steroid hormones (ecdysteroids) in mammals. J. Endocrinol. 191 (1), 1–8. doi: 10.1677/joe.1.06900.
Slama K., Koudela K., Tenora J., Mathova A. 1996. Insect hormones in vertebrates: Anabolic effects of 20-hydroxyecdysone in Japanese quails. Experientia. 52, 702–706.
Stopka P., Stancl J., Slama K. 1999. Effect of insect hormone, 20-hydroxyecdysone on growth and reproduction in mice. Acta Soc. Zool. Bohemicae. 63, 367–378.
Syrov V.N. 2000. Comparative experimental investigations of the anabolic activity of phytoecdysteroids and steranabols. Pharm. Chem. J. 34, 193–197.
Kratky F., Opletal L., Hejhalek J., Kucharova S. 1997. Effect of 20-hydroxyecdysone on the protein synthesis of pigs. Zivocisna Vyroba. 42, 445–451.
Shuvalov O., Kirdeeva Y., Fefilova E., Netsvetay S., Zorin M., Vlasova Y., Fedorova O., Daks A., Parfenyev S., Barlev N. 2023. 20-Hydroxyecdysone Confers antioxidant and antineoplastic properties in human non-small cell lung cancer cells. Metabolites. 13, 656. https://doi.org/10.3390/metabo13050656
Romaniuk-Drapała A., Lisiak N., Toton E., Matysiak A., Nawrot J., Nowak G., Kaczmarek M., Rybczyńska M., Rubiś B. 2021. Proapoptotic and proautophagic activity of 20-hydroxyecdysone in breast cancer cells in vitro. Chem. Biol. Interact. 342, 109479. doi: 10.1016/j.cbi.2021.109479.
Xia X., Zhang Q., Liu R., Wang Z., Tang N., Liu F., Huang G., Jiang X., Gui G., Wang L., Sun X. 2014. Effects of 20-hydroxyecdysone on improving memory deficits in streptozotocin-induced type 1 diabetes mellitus in rat. Eur. J. Pharmacol. 5, 740, 45–52. doi: 10.1016/j.ejphar.2014.06.026.
Mallek A., Movassat J., Ameddah S., Liu J., Semiane N., Khalkhal A., Dahmani Y. 2018. Experimental diabetes induced by streptozotocin in the desert gerbil, Gerbillus gerbillus, and the effects of short-term 20-hydroxyecdysone administration. Biomed. Pharmacother. 102, 354–361. doi: 10.1016/j.biopha.2018.03.070.
Baev A.Y., Charishnikova O.S., Khasanov F.A., Nebesnaya K.S., Makhmudov A.R., Rakhmedova M.T., Khushbaktova Z.A., Syrov V.N., Levitskaya Y.V. 2022. Ecdysterone prevents negative effect of acute immobilization stress on energy metabolism of rat liver mitochondria. J. Steroid Biochem. Mol. Biol. 219, 106066. doi: 10.1016/j.jsbmb.2022.106066.
Parr M.K., Botre F., Nass A., Hengevoss J., Diel P., Wolber G. 2015. Ecdysteroids: A novel class of anabolic agents? Biol. Sport. 32, 169–173.
Wang J., Green P.S., Simpkins J.W. 2001. Estradiol protects against ATP depletion, mitochondrial membrane potential decline and the generation of reactive oxygen species induced by 3-nitroproprionic acid in SK-N-SH human neuroblastoma cells. J. Neurochem. 77 (3), 804–811. doi: 10.1046/j.1471–4159.2001.00271.x.
Nilsen J., Diaz Brinton R. 2003. Mechanism of estrogen-mediated neuroprotection: Regulation of mitochondrial calcium and Bcl-2 expression. Proc. Natl. Acad. Sci. USA. 100 (5), 2842–2847. doi: 10.1073/pnas.0438041100.
Burstein S.R., Kim H.J., Fels J.A., Qian L., Zhang S., Zhou P., Starkov A.A., Iadecola C., Manfredi G. 2018. Estrogen receptor beta modulates permeability transition in brain mitochondria. Biochim. Biophys. Acta. Bioenerg. 1859 (6), 423–433. doi: 10.1016/j.bbabio.2018.03.006.
Dubinin M.V., Ilzorkina A.I., Salimova E.V., Landage M.S., Khoroshavina E.I., Gudkov S.V., Belosludtsev K.N., Parfenova L.V. 2023. Effect of fusidic acid and some nitrogen-containing derivatives on liposomal and mitochondrial membranes. Membranes (Basel). 13 (10), 835. doi: 10.3390/membranes13100835.
Dubinin M.V., Nedopekina D.A., Ilzorkina A.I., Semenova A.A., Sharapov V.A., Davletshin E.V., Mikina N.V., Belsky Y.P., Spivak A.Y., Akatov V.S., Belosludtseva N.V., Liu J., Belosludtsev K.N. 2023. Conjugation of triterpenic acids of ursane and oleanane types with mitochondria-targeting cation F16 synergistically enhanced their cytotoxicity against tumor cells. Membranes (Basel). 13 (6), 563. doi: 10.3390/membranes13060563.
Dubinin M.V., Semenova A.A., Ilzorkina A.I., Mikheeva I.B., Yashin V.A., Penkov N.V., Vydrina V.A., Ishmuratov G.Y., Sharapov V.A., Khoroshavina E.I., Gudkov S.V., Belosludtsev K.N. 2020. Effect of betulin and betulonic acid on isolated rat liver mitochondria and liposomes. Biochim. Biophys. Acta. Biomembr. 1862 (10), 183383. doi: 10.1016/j.bbamem.2020.183383.
Dubinin M.V., Talanov E.Y., Tenkov K.S., Starinets V.S., Mikheeva I.B., Sharapov M.G., Belosludtsev K.N. 2020. Duchenne muscular dystrophy is associated with the inhibition of calcium uniport in mitochondria and an increased sensitivity of the organelles to the calcium-induced permeability transition. Biochim. Biophys. Acta. Mol. Basis Dis. 1866 (5), 165674. doi: 10.1016/j.bbadis.2020.165674.
Dubinin M.V., Svinin A.O., Vedernikov A.A., Starinets V.S., Tenkov K.S., Belosludtsev K.N., Samartsev V.N. 2019. Effect of hypothermia on the functional activity of liver mitochondria of grass snake (Natrix natrix): Inhibition of succinate-fueled respiration and K⁺ transport, ROS-induced activation of mitochondrial permeability transition. J. Bioenerg. Biomembr. 51 (3), 219–229.
Chance B., Williams G.R. 1955. Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J. Biol. Chem. 217 (1), 383–393.
Spinazzi M., Casarin A., Pertegato V., Salviati L., Angelini C. 2012. Assessment of mitochondrial respiratory chain enzymatic activities on tissues and cultured cells. Nat. Protoc. 7 (6), 1235–1246. https://doi.org/10.1038/nprot.2012.058.
Dubinin M.V., Sharapov V.A., Ilzorkina A.I., Efimov S.V., Klochkov V.V., Gudkov S.V., Belosludtsev K.N. 2022. Comparison of structural properties of cyclosporin A and its analogue alisporivir and their effects on mitochondrial bioenergetics and membrane behavior. Biochim. Biophys. Acta Biomembr. 864 (9), 183972.
Dubinin M.V., Talanov E.Y., Tenkov K.S., Starinets V.S., Mikheeva I.B., Belosludtsev K.N. 2020. Transport of Ca²⁺ and Ca²⁺-dependent permeability transition in heart mitochondria in the early stages of Duchenne muscular dystrophy. Biochim. Biophys. Acta. Bioenergetics. 1861 (10), 148250.
Lafont R., Dinan L. 2003. Practical uses for ecdysteroids in mammals including humans: An update. J. Insect. Sci. 3, 7. doi: 10.1093/jis/3.1.7.
Андреев А.Ю., Кушнарева Ю.Е., Мерфи Э.Н., Старков А.А. 2015 Митохондриальный метаболизм активных форм кислорода: десять лет спустя (обзор). Биохимия. 80 (5), 612–630.
Щулькин А.В., Якушева Е.Н., Давыдов В.В., Дармограй В.Н. 2012. Исследование прямой антиоксидантной активности фитоэкдистерона in vitro. Рос. мед.-биол. вестн. им. акад. И.П. Павлова. 1, 51–57.
Kuzmenko А.I., Niki E., Noguchi Н. 2001. New functions of 20-hydroxyecdysone in lipid peroxidation. J. Oleo Sci. 50 (6), 497–506.
Cai Y.J., Dai J.Q., Fang J.G., Ma L.P., Hou L.F., Yang L., Liu Z.L. 2002. Antioxidative and free radical scavenging effects of ecdysteroids from Serratula strangulata. Can. J. Physiol. Pharmacol. 80 (12), 1187–1194. doi: 10.1139/y02–152.
Sahach V.F., Korkach Iu.P., Kotsiuruba A.V., Rudyk O.V., Vavilova H.L. 2008. Mitochondrial permeability transition pore opening inhibition by ecdysterone in heart mitochondria of aging rats. J. Phys. 54 (4), 3–10.
Das N., Mishra S.K., Bishayee A., Ali E.S., Bis-hayee A. 2021. The phytochemical, biological, and medicinal attributes of phytoecdysteroids: An updated review. Acta. Pharm. Sin. B. 11 (7), 1740–1766. doi: 10.1016/j.apsb.2020.10.012.
Li Y.B., Li X.R., Yang T., Wang J.X., Zhao X.F. 2016. The steroid hormone 20-hydroxyecdysone promotes switching from autophagy to apoptosis by increasing intracellular calcium levels. Insect. Biochem. Mol. Biol. 79, 73–86. doi: 10.1016/j.ibmb.2016.10.004.
Дубинин М.В., Белослудцев К.Н. 2019. Таксономические особенности механизмов специфического транспорта Ca²⁺ в митохондриях. Биол. мембраны. 36 (4), 231–241. doi: 10.1134/S0233475519040030.
Белослудцев К.Н., Дубинин М.В., Белослудцева Н.В., Миронова Г.Д. 2019. Транспорт ионов Ca²⁺ митохондриями: механизмы, молекулярные структуры и значение для клетки. Биохимия. 84 (6), 759–775.
Rasola A., Bernardi P. 2011. Mitochondrial permeability transition in Ca²⁺-dependent apoptosis and necrosis. Cell Calcium. 50, 222–233.