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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

Research Article

Study of the Effect of Palmitic Acid on the Expression of Myostatin mRNA and its Cytotoxic Properties in the Culture of Myoblast Cells and the Possibility of Exogenous Regulation

Author(s): Vladimir G. Kukes, Vladimir A. Furalyov, Albina А. Gazdanova, Olga K. Parfenova*, Dmitry V. Grishin and Nikita G. Sidorov

Volume 20, Issue 6, 2024

Published on: 25 October, 2023

Article ID: e251023222649 Pages: 6

DOI: 10.2174/0115734072273072231017104102

Price: $65

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Abstract

Objective: To study the cytotoxic effect of palmitic acid on myoblasts in vitro and the influence of this toxicant on the expression of myostatin mRNA in myoblast culture.

Methods: To research the protective action against these processes of a compound with antioxidant activity, for which 2-ethyl-6-methyl-3-hydroxypyridine malate (ethoxidol) was chosen.

Results: Our studies have shown that palmitic acid has a noticeable cytostatic effect on myoblasts in vitro, significantly suppressing their proliferation: the rate of MTT recovery in myoblasts treated with palmitate was only 9.6% of that rate in control myoblasts. In experiments, it was shown that palmitic acid slightly activated the expression of myostatin mRNA. At the same time, the protective effect of 2-ethyl-6-methyl-3-hydroxypyridine malate was not so pronounced.

Conclusion: The results of our research indicate that the activation of myostatin synthesis is not one of the main causes of the development of myodystrophy in obese people or people following a high-lipid diet, while the direct cytotoxic effect of palmitic acid on myoblasts is. It is obvious that the use of antioxidants such as ethoxidol has a protective effect on myoblasts in the experiment and may have a certain potential in clinical practice.

Graphical Abstract

[1]
Carta, G.; Murru, E.; Banni, S.; Manca, C. Palmitic acid: Physiological role, metabolism and nutritional implications. Front. Physiol., 2017, 8, 902.
[http://dx.doi.org/10.3389/fphys.2017.00902] [PMID: 29167646]
[2]
Foley, S.; Miller, E.; Braziel, S.; Lee, S. Molecular organization in mixed SOPC and SDPC model membranes: Water permeability studies of polyunsaturated lipid bilayers. Biochim. Biophys. Acta Biomembr., 2020, 1862(9), 183365.
[http://dx.doi.org/10.1016/j.bbamem.2020.183365] [PMID: 32454009]
[3]
Mironova, G.D.; Pavlov, E.V. Mitochondrial Cyclosporine A-Independent Palmitate/Ca2+ - Induced Permeability Transition Pore (PA-mPT Pore) and Its Role in Mitochondrial Function and Protection against Calcium Overload and Glutamate Toxicity. Cells, 2021, 10, 125.
[4]
Wang, N.; Ma, H.; Li, J.; Meng, C.; Zou, J.; Wang, H.; Liu, K.; Liu, M.; Xiao, X.; Zhang, H.; Wang, K. HSF1 functions as a key defender against palmitic acid-induced ferroptosis in cardiomyocytes. J. Mol. Cell. Cardiol., 2021, 150, 65-76.
[http://dx.doi.org/10.1016/j.yjmcc.2020.10.010] [PMID: 33098823]
[5]
Fan, Z.; Xiao, Q. Impaired autophagic flux contributes to muscle atrophy in obesity by affecting muscle degradation and regeneration. Biochem. Biophys. Res. Commun., 2020, 525(2), 462-468.
[http://dx.doi.org/10.1016/j.bbrc.2020.02.110] [PMID: 32102751]
[6]
Guo, A.; Li, K.; Xiao, Q. Sarcopenic obesity: Myokines as potential diagnostic biomarkers and therapeutic targets? Exp. Gerontol., 2020, 139, 111022.
[http://dx.doi.org/10.1016/j.exger.2020.111022] [PMID: 32707318]
[7]
Furalyov, V.A.; Kukes, V.G.; Gazdanova, A.A. A study of cytotoxic effect of the uremic toxin indoxyl sulfate on myoblasts in vitro, the expression of myostatin mRNA in myoblast cell culture, and the possibility of exogenous regulation. Nephrology and Dialysis, 2021, 23(2), 219-224.
[http://dx.doi.org/10.28996/2618-9801-2021-2-219-224]
[8]
Furalyov, V.A. Kukes, V.G.; Gazdanova, A.A.; Parfenova, O.K.; Sidorov, N.G.; Kurkin, R.V. Study of the protective properties of 2-ethyl-6-methyl-3-hydroxypyridine malate in the model of in vitro-induced oxidative stress in myoblast cell culture. Curr. Bioact. Compd., 2023, 19(6), e221122211123.
[http://dx.doi.org/10.2174/1573407219666221122122346]
[9]
Denizot, F.; Lang, R. Rapid colorimetric assay for cell growth and survival. J. Immunol. Methods, 1986, 89(2), 271-277.
[http://dx.doi.org/10.1016/0022-1759(86)90368-6] [PMID: 3486233]
[10]
Artaza, J.N.; Bhasin, S.; Magee, T.R.; Reisz-Porszasz, S.; Shen, R.; Groome, N.P.; Fareez, M.M.; Gonzalez-Cadavid, N.F. Myostatin inhibits myogenesis and promotes adipogenesis in C3H 10T(1/2) mesenchymal multipotent cells. Endocrinology, 2005, 146(8), 3547-3557.
[http://dx.doi.org/10.1210/en.2005-0362] [PMID: 15878958]
[11]
Lee, H.; Lim, J.Y.; Choi, S.J. Oleate prevents palmitate-induced atrophy via modulation of mitochondrial ros production in skeletal myotubes. Oxid. Med. Cell. Longev., 2017, 2017, 1-11.
[http://dx.doi.org/10.1155/2017/2739721] [PMID: 28947926]
[12]
Wu, K.M.; Hsu, Y.M.; Ying, M.C.; Tsai, F.J.; Tsai, C.H.; Chung, J.G.; Yang, J.S.; Tang, C.H.; Cheng, L.Y.; Su, P.H.; Viswanadha, V.P.; Kuo, W.W.; Huang, C.Y. High-density lipoprotein ameliorates palmitic acid-induced lipotoxicity and oxidative dysfunction in H9c2 cardiomyoblast cells via ROS suppression. Nutr. Metab. , 2019, 16(1), 36.
[http://dx.doi.org/10.1186/s12986-019-0356-5] [PMID: 31149020]
[13]
Wende, A.R.; Abel, E.D. Lipotoxicity in the heart. Biochim. Biophys. Acta Mol. Cell Biol. Lipids, 2010, 1801(3), 311-319.
[http://dx.doi.org/10.1016/j.bbalip.2009.09.023] [PMID: 19818871]
[14]
Benáková, Š.; Holendová, B.; Plecitá-Hlavatá, L. Redox homeostasis in pancreatic β-cells: From development to failure. Antioxidants, 2021, 10(4), 526.
[http://dx.doi.org/10.3390/antiox10040526] [PMID: 33801681]
[15]
Yu, G.; Luo, H.; Zhang, N.; Wang, Y.; Li, Y.; Huang, H.; Liu, Y.; Hu, Y.; Liu, H.; Zhang, J.; Tang, Y.; Huang, Y. Loss of p53 sensitizes cells to palmitic acid-induced apoptosis by reactive oxygen species accumulation. Int. J. Mol. Sci., 2019, 20(24), 6268.
[http://dx.doi.org/10.3390/ijms20246268] [PMID: 31842349]
[16]
Kong, J.Y.; Rabkin, S.W. Lovastatin does not accentuate but is rather additive to palmitate-induced apoptosis in cardiomyocytes. Prostaglandins Leukot. Essent. Fatty Acids, 2002, 67(5), 293-302.
[http://dx.doi.org/10.1054/plef.2002.0432] [PMID: 12445488]
[17]
Belosludtsev, K.N.; Dubinin, M.V.; Belosludtseva, N.V.; Mironova, G.D. Mitochondrial CA2+ transport: Mechanisms, molecular structures, and role in cells. Biochemistry, 2019, 84(6), 593-607.
[http://dx.doi.org/10.1134/S0006297919060026] [PMID: 31238859]
[18]
Belosludtsev, K.N.; Trudovishnikov, A.S.; Belosludtseva, N.V.; Agafonov, A.V.; Mironova, G.D. Palmitic acid induces the opening of a Ca2+-dependent pore in the plasma membrane of red blood cells: The possible role of the pore in erythrocyte lysis. J. Membr. Biol., 2010, 237(1), 13-19.
[http://dx.doi.org/10.1007/s00232-010-9302-1] [PMID: 20835705]
[19]
Deng, B.; Zhang, F.; Wen, J.; Ye, S.; Wang, L.; Yang, Y.; Gong, P.; Jiang, S. The function of myostatin in the regulation of fat mass in mammals. Nutr. Metab. , 2017, 14(1), 29.
[http://dx.doi.org/10.1186/s12986-017-0179-1] [PMID: 28344633]
[20]
Chandra, K.; Jain, V.; Jain, S.K. Plasma non-esterified fatty acids (NEFA) in type 2 diabetes mellitus: Evidence on pathophysiology. J Diabetes Clin Res., 2021, 3(2), 46-50.
[21]
Liu, X.; Zeng, X.; Chen, X.; Luo, R.; Li, L.; Wang, C.; Liu, J.; Cheng, J.; Lu, Y.; Chen, Y. Oleic acid protects insulin-secreting INS-1E cells against palmitic acid-induced lipotoxicity along with an amelioration of ER stress. Endocrine, 2019, 64(3), 512-524.
[http://dx.doi.org/10.1007/s12020-019-01867-3] [PMID: 30778898]
[22]
Ogawa, Y.; Imajo, K.; Honda, Y.; Kessoku, T.; Tomeno, W.; Kato, S.; Fujita, K.; Yoneda, M.; Saito, S.; Saigusa, Y.; Hyogo, H.; Sumida, Y.; Itoh, Y.; Eguchi, K.; Yamanaka, T.; Wada, K.; Nakajima, A. Palmitate-induced lipotoxicity is crucial for the pathogenesis of nonalcoholic fatty liver disease in cooperation with gut-derived endotoxin. Sci. Rep., 2018, 8(1), 11365.
[http://dx.doi.org/10.1038/s41598-018-29735-6] [PMID: 30054551]
[23]
Ruiz, M.; Henricsson, M.; Borén, J.; Pilon, M. Palmitic acid causes increased dihydroceramide levels when desaturase expression is directly silenced or indirectly lowered by silencing AdipoR2. Lipids Health Dis., 2021, 20(1), 173.
[http://dx.doi.org/10.1186/s12944-021-01600-y] [PMID: 34839823]
[24]
Sarnyai, F.; Donkó, M.B.; Mátyási, J.; Gór-Nagy, Z.; Marczi, I.; Simon-Szabó, L.; Zámbó, V.; Somogyi, A.; Csizmadia, T. Lőw, P.; Szelényi, P.; Kereszturi, É.; Tóth, B.; Csala, M. Cellular toxicity of dietary trans fatty acids and its correlation with ceramide and diglyceride accumulation. Food Chem. Toxicol., 2019, 124, 324-335.
[http://dx.doi.org/10.1016/j.fct.2018.12.022] [PMID: 30572061]
[25]
Jęśko, H.; Stępień, A.; Lukiw, W.J.; Strosznajder, R.P. The cross-talk between sphingolipids and insulin-like growth factor signaling: Significance for aging and neurodegeneration. Mol. Neurobiol., 2019, 56(5), 3501-3521.
[http://dx.doi.org/10.1007/s12035-018-1286-3] [PMID: 30140974]
[26]
Inokuchi, J.; Kanoh, H. Pathophysiological Significance of GM3 Ganglioside Molecular Species With a Particular Attention to the Metabolic Syndrome Focusing on Toll-Like Receptor 4 Binding. Front. Mol. Biosci., 2022, 9, 918346.
[http://dx.doi.org/10.3389/fmolb.2022.918346] [PMID: 35712350]
[27]
Hyde, R.; Hajduch, E.; Powell, D.J.; Taylor, P.M.; Hundal, H.S. Ceramide down-regulates System A amino acid transport and protein synthesis in rat skeletal muscle cells. FASEB J., 2005, 19(3), 1-24.
[http://dx.doi.org/10.1096/fj.04-2284fje] [PMID: 15611152]
[28]
Kukes, V.G.; Parfenova, O.K.; Romanov, B.K.; Prokofiev, A.B.; Parfenova, E.V.; Sidorov, N.G.; Gazdanova, A.A.; Pavlova, L.I.; Zozina, V.I.; Andreev, A.D.; Aleksandrova, T.V.; Chernova, S.V.; Ramenskaya, G.V. The mechanism of action of ethoxidol on oxidative stress indicesin heart failure and hypotension. Sovrem. Tekhnologii Med., 2020, 12(2), 67-72.
[http://dx.doi.org/10.17691/stm2020.12.2.08] [PMID: 34513055]
[29]
Kukes, V.G. The mechanism of action of follistatin-like protein-1 (FSTL-1). The Bulletin of the Scientific Centre for Expert Evaluation of Medicinal Products, 2019, 9(4), 256-260.
[http://dx.doi.org/10.30895/1991-2919-2019-9-4-256-260]
[30]
Parfenova, E.V.; Zubkova, E.S.; Boldyreva, M.A.; Tsokolaeva, Z.I.; Olefir, Yu.V.; Romanov, B.K.; Prokofiev, A.B.; Kukes, V.G.; Goroshko, O.A.; Aleksandrova, T.V.; Gazdanova, A.A.; Parfenova, O.K.; Sidorov, N.G.; Andreev, A.D. Study of the influence of etoxidol on expression of follistatin-like protein-1 (FSTL -1) in myocardium after experimental infarction in rats. Biomedicinskayahimiya., 2020, 66(3), 250-256.
[http://dx.doi.org/10.18097/pbmc20206603250]

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