Dexamethasone leads to Zn2+ accumulation and increased unbound Zn2+ in C2C12 muscle and 3T3-L1 adipose cells
- PMID: 36716229
- DOI: 10.1002/jcb.30376
Dexamethasone leads to Zn2+ accumulation and increased unbound Zn2+ in C2C12 muscle and 3T3-L1 adipose cells
Abstract
Skeletal muscle atrophy is associated with increases in circulating glucocorticoid levels and insulin resistance. Zinc accumulates in atrophic muscle, but the relationship between atrophy, insulin resistance, and Zn2+ homeostasis remains unclear. In this study, the effect of the glucocorticoid dexamethasone (DEX) on insulin and Zn2+ homeostasis was explored. Treatment of differentiated C2C12 skeletal myotubes and 3T3-L1 adipocytes with DEX significantly increased mRNA expression of the metal-binding proteins Mt1 and 2 and altered energy storage as shown by the increased size of lipid droplets in 3T3-L1 cells. In C2C12 cells the total cellular Zn2+ was higher after DEX treatment, and in both C2C12 and 3T3-L1 adipocytes, free unbound Zn2+ was increased. Insulin treatment led to a gradual increase in free Zn2+ in C2C12 cells, and no significant change in DEX-treated cells such that concentrations were similar 10 min after insulin treatment. These data demonstrate that DEX disturbs Zn2+ homeostasis in muscle and fat cells. Further study of the molecular pathways involved to identify novel therapeutic targets for treatment of skeletal muscle atrophy is warranted.
Keywords: dexamethasone; glucocorticoids; insulin; zinc.
© 2023 The Authors. Journal of Cellular Biochemistry published by Wiley Periodicals LLC.
References
REFERENCES
-
- Schakman O, Kalista S, Barbé C, Loumaye A, Thissen JP. Glucocorticoid-induced skeletal muscle atrophy. Int J Biochem Cell Biol. 2013;45(10):2163-2172. doi:10.1016/j.biocel.2013.05.036
-
- Siren PMA, Siren MJ. Systemic zinc redistribution and dyshomeostasis in cancer cachexia. J Cachexia Sarcopenia Muscle. 2010;1(1):23-33. doi:10.1007/s13539-010-0009-z
-
- Bodine SC, Furlow JD. Glucocorticoids and skeletal muscle. Adv Exp Med Biol. 2015;872:145-176. doi:10.1007/978-1-4939-2895-8_7
-
- Geer EB, Islam J, Buettner C. Mechanisms of glucocorticoid-induced insulin resistance. Endocrinol Metab Clin North Am. 2014;43(1):75-102. doi:10.1016/j.ecl.2013.10.005
-
- Baracos VE. Hypercatabolism and hypermetabolism in wasting states. Curr Opin Clin Nutr Metab Care. 2002;5(3):237-239.
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