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Cytoprotective Effect of Zinc-Mediated Antioxidant Gene Expression on Cortisol-Induced Cytotoxicity

Cortisol 유발 세포독성에 대한 아연 관련 항산화 유전자 발현 증가에 의한 세포보호 효과

  • Received : 2015.03.17
  • Accepted : 2015.03.31
  • Published : 2015.05.31

Abstract

The protective effect of zinc against cortisol-induced cell injury was examined in rainbow trout gill epithelial cells. Cells exposed to cortisol for 24 h showed increased leakage of lactate dehydrogenase (LDH) as well as decreased cell viability in a dose-dependent manner. Treatment with zinc ($100{\mu}M$ $ZnSO_4$) reduced the severity of both LDH release and cell death as well as protected cells against cortisol-induced caspase-3 activation, indicating reduction of apoptosis. Cortisol-induced cell death, leakage of LDH, and caspase-3 activation were blocked by the glucocorticoid receptor antagonist Mifepristone (RU-486), suggesting that cell injury was cortisol-dependent. In addition, we studied the effect of zinc on the expression of antioxidant genes such as metallothionein A (MTA), metallothionein B (MTB), glutathione-S-transferase (GST), and glucose-6-phosphate dehydrogenase (G6PD) during cortisol-induced cell injury. MTA, MTB, GST, and G6PD mRNA levels increased after treatment with zinc or cortisol, separately or in combination. Higher mRNA levels of MTA, MTB, GST, and G6PD were detected when cells were treated with $100{\mu}M$ $ZnSO_4$ and $1{\mu}M$ cortisol in combination at the same time compared to treatment with zinc or cortisol separately. Cells treated with zinc showed increased intracellular free zinc concentrations, and this response was significantly enhanced in cells treated with cortisol and zinc. In conclusion, zinc treatment inhibited cortisol-induced cytotoxicity and apoptosis through indirect antioxidant action.

References

  1. Chung MJ, Walker PA, Brown RW, Hogstrand C. 2005. ZINC-mediated gene expression offers protection against $H_2O_2$-induced cytotoxicity. Toxicol Appl Pharmacol 205: 225-236. https://doi.org/10.1016/j.taap.2004.10.008
  2. Chung MJ, Walker PA, Hogstrand C. 2006. Dietary phenolic antioxidants, caffeic acid and Trolox, protect rainbow trout gill cells from nitric oxide-induced apoptosis. Aquat Toxicol 80: 321-328. https://doi.org/10.1016/j.aquatox.2006.09.009
  3. Chung MJ, Hogstrand C, Lee SJ. 2006. Cytotoxicity of nitric oxide is alleviated by zinc-mediated expression of antioxidant genes. Exp Biol Med 231: 1555-1563. https://doi.org/10.1177/153537020623100916
  4. Bury NR, Chung MJ, Sturm A, Walker PA, Hogstrand C. 2008. Cortisol stimulates the zinc signaling pathway and expression of metallothioneins and ZnT1 in rainbow trout gill epithelial cells. Am J Physiol Regul Integr Comp Physiol 294: R623-R629.
  5. Cherian MG, Jayasurya A, Bay BH. 2003. Metallothioneins in human tumors and potential roles in carcinogenesis. Mutat Res 533: 201-209. https://doi.org/10.1016/j.mrfmmm.2003.07.013
  6. Bae YJ, Kim MH, Yeon JY. 2012. Evaluation of dietary zinc, copper, manganese and selenium intake in female university students. Korean J Community Nutr 17: 146-155. https://doi.org/10.5720/kjcn.2012.17.2.146
  7. Kim MG, Kim YS, Kim YS, Lee SB, Ryu KS, Yoon MH, Lee JB. 2014. A study on the content of minerals in fortified food. J Fd Hyg Safety 29: 99-104. https://doi.org/10.13103/JFHS.2014.29.2.099
  8. Son YW, Choi YS. 2012. Protection of Chenopodium album var. centrorubrum extract by oxidative effect in cultured human skin fibroblasts damaged by cadmium. J Korean Soc People Plants Environ 15: 155-161.
  9. Limberaki E, Eleftheriou P, Gasparis G, Karalekos E, Kostoglou V, Petrou C. 2011. Cortisol levels and serum antioxidant status following chemotherapy. Health 3: 512-517. https://doi.org/10.4236/health.2011.38085
  10. Stark J1, Tulassay Z, Lengyel G, Szombath D, Szekacs B, Adler I, Marczell I, Nagy-Repas P, Dinya E, Racz K, Bekesi G. 2013. Increased total scavenger capacity in rats fed corticosterone and cortisol on lipid-rich diet. Acta Physiol Hung 100: 84-88. https://doi.org/10.1556/APhysiol.99.2012.001
  11. Johanssen S, Allolio B. 2007. Mifepristone (RU 486) in Cushing's syndrome. Eur J Endocrinol 157: 561-569. https://doi.org/10.1530/EJE-07-0458
  12. Pagniello KB, Bols NC, Lee LEJ. 2002. Effect of corticosteroids on viability and proliferation of the rainbow trout monocyte/macrophage cell line, RTS11. Fish Shellfish Immunol 13: 199-214. https://doi.org/10.1006/fsim.2001.0395
  13. Brandao-Neto J, de Mendonca BB, Shuhama T, Marchini JS, Pimenta WP, Tornero MT. 1990. Zinc acutely and temporarily inhibits adrenal cortisol secretion in humans. A preliminary report. Biol Trace Elem Res 24: 83-89. https://doi.org/10.1007/BF02789143
  14. Elenkov IJ, Chrousos GP. 2002. Stress hormones, proinflammatory and antiinflammatory cytokines, and autoimmunity. Ann N Y Acad Sci 966: 290-303. https://doi.org/10.1111/j.1749-6632.2002.tb04229.x
  15. Amsterdam A, Tajima K, Sasson R. 2002. Cell-specific regulation of apoptosis by glucocorticoids: implication to their anti-inflammatory action. Biochem Pharmacol 64: 843-850. https://doi.org/10.1016/S0006-2952(02)01147-4
  16. Byun YJ, Eun CS. 2014. Psychological stress in chronic intestinal diseases. Hanyang Med Rev 34: 66-71. https://doi.org/10.7599/hmr.2014.34.2.66
  17. Holsboer F. 2001. Stress, hypercortisolism and corticosteroid receptors in depression: implications for therapy. J Affect Disord 62: 77-91. https://doi.org/10.1016/S0165-0327(00)00352-9
  18. Jeon JH, Kim SH. 2012. Depression, stress and how they are related with health behaviors and metabolic syndrome among woman over 40 years. J Korean Soc Matern Child Health 16: 263-273. https://doi.org/10.21896/jksmch.2012.16.2.263
  19. Jin SI, Kim HJ, Jeong JH, Jin DE, Choi SG, Heo HJ. 2014. Nutritional composition and cytoprotective effect of Moringa oleifera Lam. Korean J Food Sci Technol 46: 609-615. https://doi.org/10.9721/KJFST.2014.46.5.609
  20. Kim MJ, Park E. 2012. Antioxidant and antigenotoxic effect of Schizandra chinensis B. extracted with water at various temperatures. Cancer Prev Res 17: 128-140.
  21. Jeong YJ, Kang KJ. 2011. Effect of Angelica keiskei extract on apoptosis of MDA-MB-231 human breast cancer cells. J Korean Soc Food Sci Nutr 40: 1654-1661. https://doi.org/10.3746/jkfn.2011.40.12.1654
  22. Choi HN, Chung MJ, Park JK, Park YI. 2013. Neuroprotective effects of N-acetylglucosamine against hydrogen peroxide-induced apoptosis in human neuronal SK-N-SH cells by inhibiting the activation of caspase-3, PARP, and p38. Food Sci Biotechnol 22: 853-858. https://doi.org/10.1007/s10068-013-0155-0
  23. Kim SH, Choi HJ, Oh HT, Chung MJ, Cui CB, Ham SS. 2008. Cytoprotective effect by antioxidant activity of Codonopsis lanceolata and Platycodon grandiflorum ethyl acetate fraction in human HepG2 cells. Korean J Food Sci Technol 40: 696-701.
  24. Kim SH, Chung MJ, Jang HD, Ham SS. 2010. Antioxidative activities of the Codonopsis lanceolata extract in vitro and in vivo. J Korean Soc Food Sci Nutr 39: 193-202. https://doi.org/10.3746/jkfn.2010.39.2.193
  25. Choi HJ, Kim SH, Oh HT, Chung MJ, Cui CB, Ham SS. 2008. Effects of Adenophora triphylla ethylacetate extract on mRNA levels of antioxidant enzymes in human HepG2 cells. J Korean Soc Food Sci Nutr 37: 1238-1243. https://doi.org/10.3746/jkfn.2008.37.10.1238