Skip to main content
SpringerLink
Log in

Differential Regulation of CuZnSOD Expression in Rat Brain by Acute and/or Chronic Stress

  • Original Paper
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Neuroendocrine stress (NES) causes increase of glucocorticoids and alters physiological levels of reactive oxygen species production in cells, which might involve modifications in the antioxidant defense system. We investigated the hypothesis that acute, chronic, or combined stress alters copper–zinc superoxide dismutase (CuZnSOD) expression pattern at both, mRNA and subcellular protein level in the cerebral cortex and hippocampus of rats and that there may be a relationship between stress-induced corticosterone and CuZnSOD expression. The most effective stress model which led to the most pronounced changes in CuZnSOD expression patterns was also investigated. Our results demonstrated that acute stress immobilization up-regulates mRNA expression of hippocampal CuZnSOD, while cytosolic protein expression of this enzyme was increased in both brain structures. Chronic stress isolation had no effect on either mRNA and protein expression level and caused a lack of significant up-regulation to a novel acute stressors. The presence of this protein in nuclear fractions of both brain structures was also confirmed. The elevated cytosolic CuZnSOD protein levels following acute immobilization might reflect on the defense system against oxidative stress. Chronic isolation compromises CuZnSOD protein expression, which may lead to the inefficient defense against reactive oxygen species (ROS). The stress-triggered CuZnSOD protein expression was not correlated by the corresponding mRNA. The results suggest that different stress models exert a different degree of influence on mRNA and protein level of CuZnSOD in both brain structures as well as serum corticosterone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  • Bowie A, O’Neill LA (2000) Oxidative stress and nuclear factor-kappaB activation: a reassessment of the evidence in the light of recent discoveries. Biochem Pharmacol 59(1):13–23. doi:10.1016/S0006-2952(99)00296-8

    Article  PubMed  CAS  Google Scholar 

  • Chang LY, Slot JW, Geuze HJ, Crapo JD (1988) Molecular immunocytochemistry of CuZn superoxide dismutase in rat hepatocytes. J Cell Biol 107:2169–2179. doi:10.1083/jcb.107.6.2169

    Article  PubMed  CAS  Google Scholar 

  • Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162(1):156–159. doi:10.1016/0003-2697(87)90021-2

    Article  PubMed  CAS  Google Scholar 

  • Chourbaji S, Zacher C, Sanchis-Segura C, Spanagel R, Gass P (2005) Social and structural housing conditions influence the development of a depressive-like phenotype in the learned helplessness paradigm in male mice. Behav Brain Res 164(1):100–106. doi:10.1016/j.bbr.2005.06.003

    Article  PubMed  Google Scholar 

  • Dronjak S, Gavrilović L, Filipović D, Radojčić BM (2004) Immobilization and cold stress affect sympatho-adrenomedular system and pituitary-adrenocortical axis of rats exposed to long-term isolation and crowding. Physiol Behav 81:409–415. doi:10.1016/j.physbeh.2004.01.011

    Article  PubMed  CAS  Google Scholar 

  • Filipović D, Radojčić BM (2005) CuZn superoxide dismutase in the hippocampus and brain cortex of rats exposed to various stress conditions. Ann NY Acad Sci 1048:366–368. doi:10.1196/annals.1342.040

    Article  PubMed  CAS  Google Scholar 

  • Filipović D, Gavrilović L, 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  CAS  Google Scholar 

  • Fridovich I (1995) Superoxide radical and superoxide dismutases. Annu Rev Biochem 64:97–112. doi:10.1146/annurev.bi.64.070195.000525

    Article  PubMed  CAS  Google Scholar 

  • Furukawa Y, O’halloran YT (2006) Posttranslational modifications in Cu, Zn-superoxide dismutase and mutations associated with amyotrophic lateral sclerosis. Antioxid Redox Signal 8(5–6):847–867. doi:10.1089/ars.2006.8.847

    Article  PubMed  CAS  Google Scholar 

  • 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 

  • Garzon J, del Rio J (1981) Hyperactivity induced in rats by long-term 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 

  • Gass P, Reichardt HM, Strekalova T, Henn F, Tronche F (2001) Mice with targeted mutations of glucocorticoid and mineralocorticoid receptors: models for depression and anxiety? Physiol Behav 73(5):811–825. doi:10.1016/S0031-9384(01)00518-2

    Article  PubMed  CAS  Google Scholar 

  • Greenlund J, Deckwerth L, Johnson M Jr (1995) Superoxide dismutase delays neuronal apoptosis: a role for reactive oxygen species in programmed neuronal death. Neuron 14(2):303–315. doi:10.1016/0896-6273(95)90287-2

    Article  PubMed  CAS  Google Scholar 

  • Holson RR, Scallet AC, 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 

  • Huggle S, Hunsaker JC 3rd, Coyne CM, Sparks DL (1996) Oxidative stress in sudden infant death syndrome. J Child Neurol 11(6):433–438. doi:10.1177/088307389601100603

    Article  PubMed  CAS  Google Scholar 

  • Johnson SA, Fournier NM, Kalynchuk LE (2006) Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor. Behav Brain Res 168(2):280–288. doi:10.1016/j.bbr.2005.11.019

    Article  PubMed  CAS  Google Scholar 

  • 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(3):1526–1533. doi:10.1006/bbrc.1994.1877

    Article  PubMed  CAS  Google Scholar 

  • Kvetnansky R, Mikulaj L (1970) Adrenal and urinary catecholamines in rat during adaptation to repeated immobilization stress. Endocrinology 87:738–743

    PubMed  CAS  Google Scholar 

  • Liu J, Wang X, Mori A (1994) Immobilization stress-induced antioxidant defense changes in rat plasma: effect of treatment with reduced glutathione. Int J Biochem 26(4):511–517. doi:10.1016/0020-711X(94)90008-6

    Article  PubMed  CAS  Google Scholar 

  • Liu J, Wang X, Shigenaga MK, Yeo HC, Mori A, Ames BN (1996) Immobilization stress causes oxidative damage to lipid, protein, and DNA in the brain of rats. FASEB J 10:1532–1538

    PubMed  CAS  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AJ, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    PubMed  CAS  Google Scholar 

  • Lynch RE, Fridovich I (1978) Permeation of erythrocyte stroma by superoxide radical. J Biol Chem 253:4697–4699

    PubMed  CAS  Google Scholar 

  • Madan AP, DeFranco DB (1993) Bidirectional transport of glucocorticoid receptors across the nuclear envelope. Proc Natl Acad Sci USA 15:3588–3592. doi:10.1073/pnas.90.8.3588

    Article  Google Scholar 

  • Madrigal JL, Olivenza R, Moro MA, Lizasoain I, Lorenzo P, Rodrigo J, Leza JC (2001) Glutathione depletion, lipid peroxidation and mitochondrial dysfunction are induced by chronic stress in rat brain. Neuropsychopharmacology 24:420–429. doi:10.1016/S0893-133X(00)00208-6

    Article  PubMed  CAS  Google Scholar 

  • Makino Y, Okamoto K, Yoshikawa N, Aoshima M, Hirota K, Yodoi J, Umesono K, Makino I, Tanaka H (1996) Thioredoxin: a redox-regulating cellular cofactor for glucocorticoid hormone action cross talk between endocrine control of stress response and cellular antioxidant defense system. J Clin Invest 98(11):2469–2477. doi:10.1172/JCI119065

    Article  PubMed  CAS  Google Scholar 

  • 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(2):408–414. doi:10.1016/j.bbr.2006.09.017

    Article  PubMed  CAS  Google Scholar 

  • Mangiavacchi S, Masi F, Scheggi S, Leggio B, De Montis MG, Gambarana C (2001) Long-term behavioral and neurochemical effects of chronic stress exposure in rats. J Neurochem 79(6):1113–1121. doi:10.1046/j.1471-4159.2001.00665.x

    Article  PubMed  CAS  Google Scholar 

  • Markesbery R (1997) Oxidative stress hypothesis in Alzheimer’s disease. Free Radic Biol Med 23:134–147. doi:10.1016/S0891-5849(96)00629-6

    Article  PubMed  CAS  Google Scholar 

  • McCord JM, Fridovich I (1969) Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem 244:6049–6055

    PubMed  CAS  Google Scholar 

  • McIntosh LJ, Hong KE, Sapolsky RM (1998a) 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 

  • McIntosh LJ, Cortopassi KM, Sapolsky RM (1998b) Glucocorticoids may alter antioxidant enzyme capacity in the brain: kainic acid studies. Brain Res 791:215–222. doi:10.1016/S0006-8993(98)00104-8

    Article  PubMed  CAS  Google Scholar 

  • McKay LI, Cidlowski JA (2000) Corticosteroids. In: Holland JF, Frei E, Bast RC, Kufe DW, Pollock RE, Weichselbaum RR (eds) Cancer medicine, vol 54, 5th edn. Decker BC, Inc, London, pp 730–742

    Google Scholar 

  • Meyer M, Schreck R, Baeuerle PA (1993) H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J 12(5):2005–2015

    PubMed  CAS  Google Scholar 

  • 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(3):235–248. doi:10.1016/0891-5849(94)90079-5

    Article  PubMed  CAS  Google Scholar 

  • Mikawa S, Kinouchi H, Kamii H, Gobbel GT, Chen SF, Carlson E, Epstein CJ, Chan PH (1996) Attenuation of acute and chronic damage following traumatic brain injury in copper, zinc-superoxide dismutase transgenic mice. J Neurosurg 85(5):885–891

    Article  PubMed  CAS  Google Scholar 

  • Noshita N, Sugawara T, Hayashi T, Lewén A, Omar G, Chan PH (2002) Copper/zinc superoxide dismutase attenuates neuronal cell death by preventing extracellular signal-regulated kinase activation after transient focal cerebral ischemia in mice. J Neurosci 22(18):7923–7930

    PubMed  CAS  Google Scholar 

  • Pacak K, Palkovits M, Yadid G, Kvetnansky R, Kopin IJ, Goldstein DS (1998) Heterogeneous neurochemical responses to different stressors: a test of Selye’s doctrine of nonspecificity. Am J Physiol 275(4 Pt 2):R1247–R1255

    PubMed  CAS  Google Scholar 

  • Pajović SB, Pejić S, Stojiljković V, Gavrilović L, 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(4):453–460

    PubMed  Google Scholar 

  • Rae TD, Schmidt PJ, Pufahl RA, Culotta VC, O’Halloran TV (1999) Undetectable intracellular free copper: the requirement of a copper chaperone for superoxide dismutase. Science 284:805–808. doi:10.1126/science.284.5415.805

    Article  PubMed  CAS  Google Scholar 

  • Rich EL, Romero LM (2005) Exposure to chronic stress downregulates corticosterone responses to acute stressors. Am J Physiol Regul Integr Comp Physiol 288(6):R1628–R1636. doi:10.1152/ajpregu.00484.2004

    PubMed  CAS  Google Scholar 

  • Sahin E, Gümüşlü S (2004) Alterations in brain antioxidant status, protein oxidation and lipid peroxidation in response to different stress models. Behav Brain Res 155(2):241–248. doi:10.1016/j.bbr.2004.04.022

    Article  PubMed  CAS  Google Scholar 

  • Sanchez M, 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(2):579–587. doi:10.1210/en.139.2.579

    Article  PubMed  CAS  Google Scholar 

  • Schmidt KN, Amstad P, Cerutti P, Baeuerle PA (1995) The roles of hydrogen peroxide and superoxide as messengers in the activation of transcription factor NF-kappa B. Chem Biol 2:13–22. doi:10.1016/1074-5521(95)90076-4

    Article  PubMed  CAS  Google Scholar 

  • Slot JW, Geuze HJ, Freeman BA, Crapo JD (1986) Intracellular localization of the copper-zinc and manganese superoxide dismutases in rat liver parenchymal cells. Lab Invest 55:363–371

    PubMed  CAS  Google Scholar 

  • Smythies J (2000) Redox aspect of signaling by catecholamines and their metabolites. Antioxid Redox Signal 2:575–583. doi:10.1089/15230860050192332

    Article  PubMed  CAS  Google Scholar 

  • Spencer RL, Kalman BA, Cotter CS, Deak T (2000) Discrimination between changes in glucocorticoid receptor expression and activation in rat brain using western blot analysis. Brain Res 868(2):275–286. doi:10.1016/S0006-8993(00)02341-6

    Article  PubMed  CAS  Google Scholar 

  • Wilson DO, Johnson P (2000) Exercise modulates antioxidant enzyme gene expression in rat myocardium and liver. J Appl Physiol 88(5):1791–1796

    PubMed  CAS  Google Scholar 

Download references

Acknowledgment

This work was supported by the Ministry of Sciences of the Republic of Serbia, Grant 143044B.

Author information

Authors and Affiliations

  1. Laboratory of Molecular Biology and Endocrinology, Institute of Nuclear Sciences Vinča, P. O. Box 522-090, 11000, Belgrade, Serbia

    Dragana Filipović & Snežana B. Pajović

Authors
  1. Dragana Filipović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Snežana B. Pajović
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dragana Filipović.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Filipović, D., Pajović, S.B. Differential Regulation of CuZnSOD Expression in Rat Brain by Acute and/or Chronic Stress. Cell Mol Neurobiol 29, 673–681 (2009). https://doi.org/10.1007/s10571-009-9375-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-009-9375-5

Keywords

Search

Navigation