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Stress-induced alternations in CuZnSOD and MnSOD activity in cellular compartments of rat liver

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Abstract

Exposure to different stressors initiates generation of reactive oxygen species (ROS), which create harmful environment for cellular macromolecules. Superoxide dismutases (SODs) represent the first line of antioxidant defense. Hence, any alternation in their function might be potentially damaging. To better define the role of SODs, we investigated the CuZnSOD activity in cytosolic and the nuclear fraction as well as mitochondrial MnSOD activity in the liver of Wistar male rats after exposure to 2 h of acute immobilization (IM) or cold (4°C) stress, 21 days of chronic social isolation (IS) or their combination (chronic stress followed by acute stress). Serum corticosterone (CORT) was monitored as an indicator of the stress response. Acute IM stress, with elevated CORT level, led to increased hepatic CuZnSOD activity in the nuclear fraction. Chronic isolation stress, where CORT was close to control value, did not change the CuZnSOD activity either in nuclei or in cytosolic fraction, while combined stress IS+Cold led to increased cytosolic CuZnSOD activity. MnSOD activity in mitochondrial fraction was decreased in all treated groups. Data have shown that different stressors have diverse effect on hepatic CuZnSOD and MnSOD activity as well as on serum CORT level. Increased nuclear CuZnSOD activity after acute stress represents physiological response since the named activity protects cells against oxidative stress, while chronic IS stress compromises CuZnSOD function, suggesting an inefficient defense against ROS. Observed decrease of MnSOD activities indicate inadequate elimination of ROS after acute or chronic stress, which is characteristic of the oxidative stress.

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References

  1. McEwen B (2008) Central effects of stress hormones in health and disease: understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583:174–185. doi:10.1016/j.ejphar.2007.11.071

    Article  PubMed  CAS  Google Scholar 

  2. McEwen BS (2004) Protection and damage from acute and chronic stress allostasis and allostatic overload and relevance to the pathophysiology of psychiatric disorders. Ann NY Acad Sci 1032:1–7. doi:10.1196/annals.1314.001

    Article  PubMed  Google Scholar 

  3. McKay LI, Cidlowski JA (2000) Corticosteroids. In: Bast RC, Kufe DW, Pollock RE, Weichselbaum RR, Holland JF, Frei E (eds) Cancer medicine, 5th edn. Decker, London, pp 730–742

    Google Scholar 

  4. Rizza RA, Mandarino LJ, Gerich JE (1982) Cortisol-induced insulin resistance in man: impaired suppression of glucose production and stimulation of glucose utilization due to a postreceptor defect of insulin action. J Clin Endocrinol Metab 54:131–138. doi:10.1210/jcem-54-1-131

    Article  PubMed  CAS  Google Scholar 

  5. Lecocq FR, Mebane D, Madison LL (1964) The acute effect of hydrocortisone on hepatic glucose output and peripheral glucose utilization. J Clin Invest 43:237–246. doi:10.1172/JCI104908

    Article  PubMed  CAS  Google Scholar 

  6. Rolo AP, Palmeira CM (2006) Diabetes and mitochondrial function: role of hyperglycemia and oxidative stress. Toxicol Appl Pharmacol 212:167–178. doi:10.1016/j.taap.2006.01.003

    Article  PubMed  CAS  Google Scholar 

  7. Rosen DR, Siddique T, Patterson D, Figlewicz DA, Sapp P, Hentati A et al (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 362:59–62. doi:10.1038/362059a0

    Article  PubMed  CAS  Google Scholar 

  8. Van Remmen H, Ikeno Y, Hamilton M, Pahlavani M, Wolf N, Thorpe SR et al (2003) Life-long reduction in MnSOD activity results in increased DNA damage and higher incidence of cancer but does not accelerate aging. Physiol Genomics 16:29–37. doi:10.1152/physiolgenomics.00122.2003

    Article  PubMed  Google Scholar 

  9. Elchuri S, Oberley TD, Qi W, Eisenstein RS, Jackson Roberts L, Van Remmen H, Epstein CJ, Huang TT (2005) CuZnSOD deficiency leads to persistent and widespread oxidative damage and hepatocarcinogenesis later in life. Oncogene 24:367–380. doi:10.1038/sj.onc.1208207

    Article  PubMed  CAS  Google Scholar 

  10. Kim HT, Kim YH, Nam JW, Lee HJ, Rho HM, Jung G (1994) Study of 5′-flanking region of human Cu/Zn superoxide dismutase. Biochem Biophys Res Commun 201:1526–1533. doi:10.1006/bbrc.1994.1877

    Article  PubMed  CAS  Google Scholar 

  11. Valentine J, Nick H (1994) Glucocorticoids repress basal and stimulated manganese superoxide dismutase levels in rat intestinal epithelial cells. Gastroenterology 107:1662–1670

    PubMed  CAS  Google Scholar 

  12. McIntosh LJ, Hong KE, Sapolsky RM (1998) Glucocorticoids may alter antioxidant enzyme capacity in the brain: baseline studies. Brain Res 791:209–214. doi:10.1016/S0006-8993(98)00115-2

    Article  PubMed  CAS  Google Scholar 

  13. Zafir A, Banu N (2009) Modulation of in vivo oxidative status by exogenous corticosterone and restraint stress in rats. Stress 12:167–177. doi:10.1080/10253890802234168

    Article  PubMed  CAS  Google Scholar 

  14. Zaidi SMR, Al-Qirim TM, Banu N (2005) Effects of antioxidant vitamins on glutathione depletion and lipid peroxidation induced by restraint stress in the rat liver. Drugs R D 6:157–165

    Article  PubMed  CAS  Google Scholar 

  15. Kaushik S, Kaur J (2003) Chronic cold exposure affects the antioxidant defense system in various rat tissues. Clin Chim Acta 333:69–77. doi:10.1016/S0009-8981(03)00171-2

    Article  PubMed  CAS  Google Scholar 

  16. Kayatekin B, Gonenc S, Acikgoz O, Uysal N, Dayi A (2002) Effects of sprint exercise on oxidative stress in skeletal muscle and liver. Eur J Appl Physiol 87:141–144. doi:10.1007/s00421-002-0607-3

    Article  PubMed  CAS  Google Scholar 

  17. Ji LL, Stratman FW, Lardy HA (1988) Antioxidant enzyme systems in rat liver and skeletal muscle: influences of selenium deficiency, chronic training, and acute exercise. Arch Biochem Biophys 263:150–160. doi:10.1016/0003-9861(88)90623-6

    Article  PubMed  CAS  Google Scholar 

  18. Sahin E, Gumuslu S (2007) Immobilization stress in rat tissues: alterations in protein oxidation, lipid peroxidation and antioxidant defense system. Comp Biochem Physiol 144:342–347. doi:10.1016/j.cbpc.2006.10.009

    Google Scholar 

  19. Sahin E, Gumuslu S (2007) Stress-dependent induction of protein oxidation, lipid peroxidation and anti-oxidants in peripheral tissues of rats: comparison of three stress models (immobilization, cold and immobilization-cold). Clin Exp Pharmacol Physiol 34:425–431. doi:10.1111/j.1440-1681.2007.04584.x

    Article  PubMed  CAS  Google Scholar 

  20. Sahin E, Gumuslu S (2004) Cold-stress-induced modulation of antioxidant defence: role of stressed conditions in tissue injury followed by protein oxidation and lipid peroxidation. Int J Biometeorol 48:165–171. doi:10.1007/s00484-004-0205-7

    Article  PubMed  CAS  Google Scholar 

  21. Pajović SB, Pejić S, Stojiljković V, Gavrilović Lj, Dronjak S, Kanazir DT (2006) Alterations in hippocampal antioxidant enzyme activities and sympatho-adrenomedullary system of rats in response to different stress models. Physiol Res 55:453–460

    PubMed  Google Scholar 

  22. Filipović D, Mandić LM, Kanazir D, Pajović SB (2010) Acute and/or chronic stress models modulate CuZnSOD and MnSOD protein expression in rat liver. Mol Cell Biochem 338:167–174. doi:10.1007/s11010-009-0350-8

    Article  PubMed  Google Scholar 

  23. Garzon J, del Rio J (1981) Hyperactivity induced in rats by longterm isolation: further studies on a new animal model for the detection of antidepressants. Eur J Pharmacol 74:287–294. doi:10.1016/0014-2999(81)90047-9

    Article  PubMed  CAS  Google Scholar 

  24. Kvetnansky R, Mikulaj L (1970) Adrenal and urinary catecholamines in rat during adaptation to repeated immobilization stress. Endocrinology 87:738–743. doi:10.1210/endo-87-4-738

    Article  PubMed  CAS  Google Scholar 

  25. Chauveau J, Moule Y, Rouiller C (1956) Isolation of pure and unaltered liver nuclei morphology and biochemical composition. Exp Cell Res 11:317–321

    Article  PubMed  CAS  Google Scholar 

  26. Lowry OH, Rosebrough NJ, Farr AJ, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  27. Ulrich-Lai YM, Figueiredo HF, Ostrander MM, Choi DC, Engeland WC, Herman JP (2006) Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner. Am J Physiol Endocrinol Metab 291:E965–E973. doi:10.1152/ajpendo.00070.2006

    Article  PubMed  CAS  Google Scholar 

  28. Mackin P, Young AH (2004) The role of cortisol and depression: exploring new opportunities for treatments. Psychiatr Times 21:6

    Google Scholar 

  29. Miyashita T, Yamaguchi T, Motoyama K, Unno K, Nakano Y, Shimo K (2006) Social stress increases biopyrrins, oxidative metabolites of bilirubin, in mouse urine. Biochem Biophys Res Commun 349:775–780. doi:10.1016/j.bbrc.2006.08.098

    Article  PubMed  CAS  Google Scholar 

  30. Kvetnansky R, McCarty R (2000) Immobilization stress. In: Fink G (ed) Encyclopedia of stress, vol 2. Academic Press, San Diego, pp 503–506

  31. Scott LV, Dinan TG (1998) Vasopressin and the regulation of hypothalamic–pituitary–adrenal axis function: implications for the pathophysiology of depression. Life Sci 62:1985–1998. doi:10.1016/S0024-3205(98)00027-7

    Article  PubMed  CAS  Google Scholar 

  32. Goldstein DS, Pacak K, Kopin IJ (1996) Nonspecificity versus primitive specificity of stress responses. In: McCarty R, Aguilera G, Sabban E, Kvetnansky R (eds) Stress: molecular genetic and neurobiological advances, vol 1. Gordon and Breach, New York, pp 3–20

  33. Bravo C, Vargas-Suarez M, Rodriguez-Enriquez S, Loza-Tavera H, Moreno-Sanchez R (2001) Metabolic changes induced by cold stress in rat liver mitochondria. J Bioenerg Biomembr 33:289–301. doi:10.1023/A:1010655223028

    Article  PubMed  CAS  Google Scholar 

  34. Blagojević DP (2007) Antioxidant systems in supporting environmental and programmed adaptations to low temperatures. Cryo Lett 28:137–150

    Google Scholar 

  35. Pigeolet E, Corbisier P, Houbion A, Lambert D, Michiels C, Raes M, Zachary M, Remacle J (1990) Glutathione peroxidase, superoxide dismutase, and catalase inactivation by peroxides and oxygen derived free radicals. Mech Ageing Dev 51:283–297. doi:10.1016/0047-6374(90)90078-T

    Article  PubMed  CAS  Google Scholar 

  36. Williams MD, Van Remmen H, Conrad CC, Huang TT, Epstein CJ, Richardson A (1998) Increased oxidative damage is correlated to altered mitochondrial function in heterozygous manganese superoxide dismutase knockout mice. J Biol Chem 273:28510–28515. doi:10.1074/jbc.273.43.28510

    Article  PubMed  CAS  Google Scholar 

  37. Li Y, Huang TT, Carlson EJ, Melov S, Ursell PC, Olson JL, Noble LJ, Yoshimura MP, Berger C, Chan PH, Wallace DC, Epstein CJ (1995) Dilated cardiomyopathy and neonatal lethality in mutant mice lacking manganese superoxide dismutase. Nat Genet 11:376–381. doi:10.1038/ng1295-376

    Article  PubMed  CAS  Google Scholar 

  38. Furukawa Y, O’halloran YT (2006) Posttranslational modifications in Cu, Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis. Antioxid Redox Signal 8:847–867. doi:10.1089/ars.2006.8.847

    Article  PubMed  CAS  Google Scholar 

  39. Michiels C, Raes M, Toussaint O, Remacle J (1994) Importance of Se-glutathione peroxidase, catalase, and Cu/Zn-SOD for cell survival against oxidative stress. Free Radic Biol Med 17:235–248. doi:10.1016/0891-5849(94)90079-5

    Article  PubMed  CAS  Google Scholar 

  40. Olivenza R, Moro M, Lizasoain I, Lorenzo P, Fernandez AP, Rodrigo J, Bosca L, Leza JC (2000) Chronic stress induces the expression of inducible nitric oxide synthase in rat brain cortex. J Neurochem 74:785–791. doi:10.1046/j.1471-4159.2000.740785.x

    Article  PubMed  CAS  Google Scholar 

  41. Gamallo A, Villanua A, Trancho G, Fraile A (1986) Stress adaptation and adrenal activity in isolated and crowded rats. Physiol Behav 36:217–221. doi:10.1016/0031-9384(86)90006-5

    Article  PubMed  CAS  Google Scholar 

  42. Malkesman O, Maayan R, Weizman A, Weller A (2006) Aggressive behavior and HPA axis hormones after social isolation in adult rats of two different genetic animal models for depression. Behav Brain Res 175:408–414. doi:10.1016/j.bbr.2006.09.017

    Article  PubMed  CAS  Google Scholar 

  43. Holson RR, Scallet AC, Ali SF, Turner BB (1991) Isolation stress revisited: isolation-rearing effects depend on animal care methods. Physiol Behav 49:1107–1118. doi:10.1016/0031-9384(91)90338-O

    Article  PubMed  CAS  Google Scholar 

  44. Sanchez MM, Aguado F, Sanchez-Toscano F, Saphier D (1998) Neuroendocrine and immunocytochemical demonstrations of decreased hypothalamo–pituitary–adrenal axis responsiveness to restraint stress after long-term social isolation. Endocrinology 139:579–587. doi:10.1210/en.139.2.579

    Article  PubMed  CAS  Google Scholar 

  45. Boveris A, Cadenas E (2000) Mitochondrial production of hydrogen peroxide regulation by nitric oxide and the role of ubisemiquinone. IUBMB Life 50:245–250. doi:10.1080/713803732

    Article  PubMed  CAS  Google Scholar 

  46. Lawler JM, Song W (2002) Specificity of antioxidant enzyme inhibition in skeletal muscle to reactive nitrogen species donors. Biochem Biophys Res Commun 294:1093–1100. doi:10.1016/S0006-291X(02)00602-2

    Article  PubMed  CAS  Google Scholar 

  47. Filipović D, Gavrilović Lj, Dronjak S, Radojčić BM (2005) Brain glucocorticoid receptor and heat shock protein 70 in rats exposed to chronic, acute or combined stress. Neuropsychobiology 51:107–114. doi:10.1159/000084168

    Article  PubMed  Google Scholar 

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Acknowledgment

This study was supported by the Ministry of Science and Technological Development of the Republic of Serbia, Grant no. 173023.

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  1. Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Science “Vinča”, University of Belgrade, P.O. Box 522, Belgrade, Serbia

    Jelena Zlatković & Dragana Filipović

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  1. Jelena Zlatković
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Correspondence to Jelena Zlatković.

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Zlatković, J., Filipović, D. Stress-induced alternations in CuZnSOD and MnSOD activity in cellular compartments of rat liver. Mol Cell Biochem 357, 143–150 (2011). https://doi.org/10.1007/s11010-011-0884-4

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