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Taurine 8 pp 241-258 | Cite as

The Mechanism of Taurine Protection Against Endoplasmic Reticulum Stress in an Animal Stroke Model of Cerebral Artery Occlusion and Stroke-Related Conditions in Primary Neuronal Cell Culture

Conference paper
First Online:
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 776)

Abstract

Taurine is an inhibitory neurotransmitter and is one of the most abundant amino acids present in the mammalian nervous system. Taurine has been shown to provide protection against neurological diseases, such as Huntington’s disease, Alzheimer’s disease, and stroke. Ischemic stroke is one of the leading causes of death and disability in the world. It is generally believed that ischemia-induced brain injury is largely due to excessive release of glutamate resulting in excitotoxicity and cell death. Despite extensive research, there are still no effective interventions for stroke. Recently, we have shown that taurine can provide effective protection against endoplasmic reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as an in vitro model of stroke as well as the in vivo model of rat focal middle cerebral artery occlusion (MCAO). Our data showed that when primary neuronal cultures were first subjected to hypoxic conditions (0.3%, 24 h) followed by reoxygenation (21%, 24–48 h), the cell viability was greatly reduced. In the animal model of stroke (MCAO), we found that 2 h ischemia followed by 4 days reperfusion resulted in an infarct of 47.42 ± 9.86% in sections 6 mm from the frontal pole. Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6 mm to 26.76 ± 6.91% in the MCAO model. Furthermore, levels of the ER stress protein markers GRP78, caspase-12, CHOP, and p-IRE-1 which were markedly increased in both the in vitro and in vivo models significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full-length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these models.

Keywords

Endoplasmic Reticulum Stress Middle Cerebral Artery Occlusion Infarct Volume Primary Neuronal Culture Local Cerebral Blood Flow 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

ER

Endoplasmic reticulum

MCAO

Middle cerebral artery occlusion

GRP78

Glucose-regulated protein 78

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References

  1. Anelli T, Sitia R (2008) Protein quality control in the early secretory pathway. EMBO J 27:315–327PubMedCrossRefGoogle Scholar
  2. Ashwal S, Tone B, Tian HR, Cole DJ, Pearce WJ (1998) Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion. Stroke 29:1037–1046, discussion 1047PubMedCrossRefGoogle Scholar
  3. Azfer A, Niu J, Rogers LM, Adamski FM, Kolattukudy PE (2006) Activation of endoplasmic reticulum stress response during the development of ischemic heart disease. Am J Physiol Heart Circ Physiol 291:H1411–H1420PubMedCrossRefGoogle Scholar
  4. Balkan J, Kanbağli O, Hatipoğlu A, Kücük M, Cevikbaş U, Aykaç-Toker G, Uysal M (2002) Improving effect of dietary taurine supplementation on the oxidative stress and lipid levels in the plasma, liver and aorta of rabbits fed on a high-cholesterol diet. Biosci Biotechnol Biochem 66:1755–1758PubMedCrossRefGoogle Scholar
  5. Bederson JB, Pitts LH, Germano SM, Nishimura MC, Davis RL, Bartkowski HM (1986) Evaluation of 2,3,5-triphenyltetrazolium chloride as a stain for detection and quantification of experimental cerebral infarction in rats. Stroke 17:1304–1308PubMedCrossRefGoogle Scholar
  6. Benedek A, Móricz K, Jurányi Z, Gigler G, Lévay G, Hársing LG, Mátyus P, Szénási G, Albert M (2006) Use of TTC staining for the evaluation of tissue injury in the early phases of reperfusion after focal cerebral ischemia in rats. Brain Res 1116:159–165PubMedCrossRefGoogle Scholar
  7. Birdsall TC (1998) Therapeutic applications of taurine. Altern Med Rev 3:128–136PubMedGoogle Scholar
  8. Chang L, Xu J, Yu F, Zhao J, Tang X, Tang C (2004) Taurine protected myocardial mitochondria injury induced by hyperhomocysteinemia in rats. Amino Acids 27:37–48PubMedCrossRefGoogle Scholar
  9. Chen WQ, Jin H, Nguyen M, Carr J, Lee YJ, Hsu CC, Faiman MD, Schloss JV, Wu JY (2001) Role of taurine in regulation of intracellular calcium level and neuroprotective function in cultured neurons. J Neurosci Res 66:612–619PubMedCrossRefGoogle Scholar
  10. Chen X, Shen J, Prywes R (2002) The luminal domain of ATF6 senses endoplasmic reticulum (ER) stress and causes translocation of ATF6 from the ER to the Golgi. J Biol Chem 277:13045–13052PubMedCrossRefGoogle Scholar
  11. Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171–182PubMedCrossRefGoogle Scholar
  12. DeGracia DJ, Montie HL (2004) Cerebral ischemia and the unfolded protein response. J Neurochem 91:1–8PubMedCrossRefGoogle Scholar
  13. El Idrissi A (2008) Taurine increases mitochondrial buffering of calcium: role in neuroprotection. Amino Acids 34:321–328PubMedCrossRefGoogle Scholar
  14. El Idrissi A, Trenkner E (1999) Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci 19:9459–9468PubMedGoogle Scholar
  15. El Idrissi A, Trenkner E (2004) Taurine as a modulator of excitatory and inhibitory neurotransmission. Neurochem Res 29:189–197PubMedCrossRefGoogle Scholar
  16. Foos TM, Wu J-Y (2002) The role of taurine in the central nervous system and the modulation of intracellular calcium homeostasis. Neurochem Res 27:21–26PubMedCrossRefGoogle Scholar
  17. Gao G, Dou QP (2000) N-terminal cleavage of bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes bcl-2-independent cytochrome C release and apoptotic cell death. J Cell Biochem 80:53–72PubMedCrossRefGoogle Scholar
  18. Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D (2000a) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6:1099–1108PubMedCrossRefGoogle Scholar
  19. Harding HP, Zhang Y, Bertolotti A, Zeng H, Ron D (2000b) Perk is essential for translational regulation and cell survival during the unfolded protein response. Mol Cell 5:897–904PubMedCrossRefGoogle Scholar
  20. Hartung T (1998) Anti-inflammatory effects of granulocyte colony-stimulating factor. Curr Opin Hematol 5:221–225PubMedCrossRefGoogle Scholar
  21. Hussy N, Deleuze C, Pantaloni A, Desarménien MG, Moos F (1997) Agonist action of taurine on glycine receptors in rat supraoptic magnocellular neurones: possible role in osmoregulation. J Physiol 502(Pt 3):609–621PubMedCrossRefGoogle Scholar
  22. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163PubMedGoogle Scholar
  23. Jong CJ, Azuma J, Schaffer S (2011) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232PubMedCrossRefGoogle Scholar
  24. Juin P (1998) Induction of a caspase-3-like activity by calcium in normal cytosolic extracts triggers nuclear apoptosis in a cell-free system. J Biol Chem 273:17559–17564PubMedCrossRefGoogle Scholar
  25. Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13:1211–1233PubMedCrossRefGoogle Scholar
  26. Kramer M, Dang J, Baertling F, Denecke B, Clarner T, Kirsch C, Beyer C, Kipp M (2010) TTC staining of damaged brain areas after MCA occlusion in the rat does not constrict quantitative gene and protein analyses. J Neurosci Methods 187:84–89PubMedCrossRefGoogle Scholar
  27. Kumar R, Azam S, Sullivan JM, Owen C, Cavener DR, Zhang P, Ron D, Harding HP, Chen JJ, Han A, White BC, Krause GS, DeGracia DJ (2001) Brain ischemia and reperfusion activates the eukaryotic initiation factor 2alpha kinase, PERK. J Neurochem 77:1418–1421PubMedCrossRefGoogle Scholar
  28. Lousada PR (2004) Taurine prevents the neurotoxicity of -amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders. FASEB J 18:511–518CrossRefGoogle Scholar
  29. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79:1431–1568PubMedGoogle Scholar
  30. Lipton S, Paul R (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622PubMedCrossRefGoogle Scholar
  31. Lo EH, Pierce AR, Matsumoto K, Kano T, Evans CJ, Newcomb R (1998) Alterations in K  +  evoked profiles of neurotransmitter and neuromodulator amino acids after focal ischemia-reperfusion. Neuroscience 83:449–458PubMedCrossRefGoogle Scholar
  32. Longa EZ, Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20:84–91PubMedCrossRefGoogle Scholar
  33. Ma Y, Hendershot LM (2004) ER chaperone functions during normal and stress conditions. J Chem Neuroanat 28:51–65PubMedCrossRefGoogle Scholar
  34. Mattson MP (2003) Excitotoxic and excitoprotective mechanisms: abundant targets for the prevention and treatment of neurodegenerative disorders. Neuromolecular Med 3:65–94PubMedCrossRefGoogle Scholar
  35. McCollum M, Ma Z, Cohen E, Leon R, Tao R, Wu J-Y, Maharaj D, Wei J (2010) Post-MPTP treatment with granulocyte colony-stimulating factor improves nigrostriatal function in the mouse model of Parkinson’s disease. Mol Neurobiol 41:410–419PubMedCrossRefGoogle Scholar
  36. Michalk DV, Wingenfeld P, Licht C (1997) Protection against cell damage due to hypoxia and reoxygenation: the role of taurine and the involved mechanisms. Amino Acids 13:337–346CrossRefGoogle Scholar
  37. Moran J, Salazar P, Pasantes-Morales H (1987) Effect of tocopherol and taurine on membrane fluidity of retinal rod outer segments. Exp Eye Res 45:769–776PubMedCrossRefGoogle Scholar
  38. Nakagawa T, Zhu H, Morishima N, Li E, Xu J, Yankner BA, Yuan J (2000) Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-beta. Nature 403:98–103PubMedCrossRefGoogle Scholar
  39. Nakka VP, Gusain A, Mehta SL, Raghubir R (2008) Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities. Mol Neurobiol 37:7–38PubMedCrossRefGoogle Scholar
  40. Nemetski SM, Gardner LB (2007) Hypoxic regulation of Id-1 and activation of the unfolded protein response are aberrant in neuroblastoma. J Biol Chem 282:240–248PubMedCrossRefGoogle Scholar
  41. Nicholls D, Attwell D (1990) The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:462–468PubMedCrossRefGoogle Scholar
  42. Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389PubMedCrossRefGoogle Scholar
  43. O’Donnell ME, Lam TI, Tran LQ, Foroutan S, Anderson SE (2006) Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion. J Cereb Blood Flow Metab 26:1234–1249PubMedCrossRefGoogle Scholar
  44. Pan C, Giraldo GS, Prentice H, Wu J-Y (2010) Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress. J Biomed Sci 17(Suppl 1):S17PubMedCrossRefGoogle Scholar
  45. Pan C, Prentice H, Price AL, Wu J-Y (2011) Beneficial effect of taurine on hypoxia- and glutamate-induced endoplasmic reticulum stress pathways in primary neuronal culture. Amino Acids 2012(43):845–855Google Scholar
  46. Pasantes-Morales H, Arzate ME (1981) Effect of taurine on seizures induced by 4-aminopyridine. J Neurosci Res 6:465–474PubMedCrossRefGoogle Scholar
  47. Paschen W, Gissel C, Linden T, Althausen S, Doutheil J (1998) Activation of gadd153 expression through transient cerebral ischemia: evidence that ischemia causes endoplasmic reticulum dysfunction. Brain Res Mol Brain Res 60:115–122PubMedCrossRefGoogle Scholar
  48. Rich PR, Mischis LA, Purton S, Wiskich JT (2001) The sites of interaction of triphenyltetrazolium chloride with mitochondrial respiratory chains. FEMS Microbiol Lett 202:181–187PubMedCrossRefGoogle Scholar
  49. Saransaari P, Oja SS (2000) Taurine and neural cell damage. Amino Acids 19:509–526PubMedCrossRefGoogle Scholar
  50. Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99PubMedCrossRefGoogle Scholar
  51. Schäbitz W-R, Kollmar R, Schwaninger M, Juettler E, Bardutzky J, Schölzke MN, Sommer C, Schwab S (2003) Neuroprotective effect of granulocyte colony-stimulating factor after focal cerebral ischemia. Stroke 34:745–751PubMedCrossRefGoogle Scholar
  52. Schäbitz WR, Li F, Irie K, Sandage BW, Locke KW, Fisher M (1999) Synergistic effects of a combination of low-dose basic fibroblast growth factor and citicoline after temporary experimental focal ischemia. Stroke 30:427–431, discussion 431-2PubMedCrossRefGoogle Scholar
  53. Schäbitz WR, Sommer C, Zoder W, Kiessling M, Schwaninger M, Schwab S (2000) Intravenous brain-derived neurotrophic factor reduces infarct size and counterregulates Bax and Bcl-2 expression after temporary focal cerebral ischemia. Stroke 31:2212–2217PubMedCrossRefGoogle Scholar
  54. Sun M, Gu Y, Zhao Y, Xu C (2011) Protective functions of taurine against experimental stroke through depressing mitochondria-mediated cell death in rats. Amino Acids 40:1419–1429PubMedCrossRefGoogle Scholar
  55. Sun M, Xu C (2008) Neuroprotective mechanism of taurine due to up-regulating calpastatin and down-regulating calpain and caspase-3 during focal cerebral ischemia. Cell Mol Neurobiol 28:593–611PubMedCrossRefGoogle Scholar
  56. Swanson RA, Morton MT, Tsao-Wu G, Savalos RA, Davidson C, Sharp FR (1990) A semiautomated method for measuring brain infarct volume. J Cereb Blood Flow Metab 10:290–293PubMedCrossRefGoogle Scholar
  57. Szegezdi E, Logue SE, Gorman AM, Samali A (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO Rep 7:880–885PubMedCrossRefGoogle Scholar
  58. Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HMM (2005) Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington’s disease phenotype. Pharmacol Biochem Behav 82:574–582PubMedCrossRefGoogle Scholar
  59. Takahashi K, Ohyabu Y, Takahashi K, Solodushko V, Takatani T, Itoh T, Schaffer SW, Azuma J (2003) Taurine renders the cell resistant to ischemia-induced injury in cultured neonatal rat cardiomyocytes. J Cardiovasc Pharmacol 41:726–733PubMedCrossRefGoogle Scholar
  60. Taranukhin AG, Taranukhina EY, Saransaari P, Djatchkova IM, Pelto-Huikko M, Oja SS (2008) Taurine reduces caspase-8 and caspase-9 expression induced by ischemia in the mouse hypothalamic nuclei. Amino Acids 34:169–174PubMedCrossRefGoogle Scholar
  61. Urquhart N, Perry TL, Hansen S, Kennedy J (1974) Passage of taurine into adult mammalian brain. J Neurochem 22:871–872PubMedCrossRefGoogle Scholar
  62. Wade JV, Olson JP, Samson FE, Nelson SR, Pazdernik TL (1988) A possible role for taurine in osmoregulation within the brain. J Neurochem 51:740–745PubMedCrossRefGoogle Scholar
  63. Wang G-H, Jiang Z-L, Fan X-J, Zhang L, Li X, Ke K-F (2007) Neuroprotective effect of taurine against focal cerebral ischemia in rats possibly mediated by activation of both GABAA and glycine receptors. Neuropharmacology 52:1199–1209PubMedCrossRefGoogle Scholar
  64. Wang XZ, Harding HP, Zhang Y, Jolicoeur EM, Kuroda M, Ron D (1998) Cloning of mammalian Ire1 reveals diversity in the ER stress responses. EMBO J 17:5708–5717PubMedCrossRefGoogle Scholar
  65. Weant KA, Baker SN (2012) New windows, same old house: an update on acute stroke management. Adv Emerg Nurs J 34:112–121PubMedGoogle Scholar
  66. Wu J-Y, Prentice H (2010) Role of taurine in the central nervous system. J Biomed Sci 17(Suppl 1):S1PubMedCrossRefGoogle Scholar
  67. Wu J-Y, Wu H, Jin Y, Wei J, Sha D, Prentice H, Lee H-H, Lin C-H, Lee Y-H, Yang L-L (2009) Mechanism of neuroprotective function of taurine. Adv Exp Med Biol 643:169–179PubMedCrossRefGoogle Scholar
  68. Wu JY, Tang XW, Tsai WH (1992) Taurine receptor: kinetic analysis and pharmacological studies. Adv Exp Med Biol 315:263–268PubMedCrossRefGoogle Scholar
  69. Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Katayama T, Tohyama M (2001) Activation of caspase-12, an endoplastic reticulum (ER) resident caspase, through tumor necrosis factor receptor-associated factor 2-dependent mechanism in response to the ER stress. J Biol Chem 276:13935–13940PubMedGoogle Scholar
  70. Yung HW, Korolchuk S, Tolkovsky AM, Charnock-Jones DS, Burton GJ (2007) Endoplasmic reticulum stress exacerbates ischemia-reperfusion-induced apoptosis through attenuation of Akt protein synthesis in human choriocarcinoma cells. FASEB J 21:872–884PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Biomedical Sciences, Charles E. Schmidt College of MedicineFlorida Atlantic UniversityBoca RatonUSA
  2. 2.Centre of Complex Systems and Brain SciencesFlorida Atlantic UniversityBoca RatonUSA
  3. 3.Department of Neurology and Sleep Center, Shung Ho HospitalTaipei Medical UniversityTaipeiTaiwan
  4. 4.Program in Integrative BiologyFlorida Atlantic UniversityBoca RatonUSA

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