Abstract
Stroke (hypoxia) is one of the leading causes of mortality in the developed countries, and it can induce excessive glutamate release and endoplasmic reticulum (ER) stress. Taurine, as a free amino acid, present in high concentrations in a range of organs in mammals, can provide protection against multiple neurological diseases. Here, we present a study to investigate the potential protective benefits of taurine against ER stress induced by glutamate and hypoxia/reoxygenation in primary cortical neuronal cultures. We found that taurine suppresses the up-regulation of caspase-12 and GADD153/CHOP induced by hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/reoxygenation by reducing the ER stress. Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expression, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation and glutamate through suppressing ATF6 and IRE1 pathways.
Similar content being viewed by others
References
Anelli T, Sitia R (2008) Protein quality control in the early secretory pathway. EMBO J 27:315–327
Azfer A, Niu J, Rogers LM, Adamski FM, Kolattukudy PE (2006) Activation of endoplsmic reticulum stress response during the development of ischemic heart disease. Am J Physiol Heart Circ Physiol 291:H1411–H1420
Birdsall TC (1998) Therapeutic applications of taurine. Altern Med Rev 3:128–136
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 27:37–48
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 66:612–619
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 277:13045–13052
Chen K, Zhang Q, Wang J, Liu F, Mi M, Xu H, Chen F, Zeng K (2009) Taurine protects transformed rat retinal ganglion cells from hypoxia-induced apoptosis by preventing mitochondrial dysfunction. Brain Res 1279:131–138
Cheng C, Fass DM, Reynolds IJ (1999) Emergence of excitotoxicity in cultured forebrain neurons coincides with larger glutamate-stimulated [Ca2+]i increases and NMDA receptor mRNA levels. Brain Res 849:97–108
Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischaemic neuronal death. Annu Rev Neurosci 13:171–182
DeGracia DJ, Montie HL (2004) Cerebral ischemia and the unfolded protein response. J Neurochem 91:1–8
Hansen SH, Andersen ML, Cornett C, Gradinaru R, Grunnet N (2010) A role for taurine in mitochondrial function. J Biomed Sci 17(Suppl 1):S23
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 6:1099–1108
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 5:897–904
Huxtable RJ (1992) The physiological actions of taurine. Physiol Rev 72:101–163
Idrissi AE, Trenkner E (1999) Growth factors and taurine protect against excitotoxicity by stabilizing calcium homeostasis and energy metabolism. J Neurosci 19:9459–9468
Jong CJ, Azuma J, Schaffer S (2011) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids (published on line: June21, 2011)
Kaufman RJ (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13:1211–1233
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 2α kinase, PERK. J Neurochem 77:1418–1421
Ma Y, Hendershot LM (2004) ER chaperone functions during normal and stress conditions. J Chem Neuroanat 28:51–65
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 13:337–346
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 403:98–103
Nemetski SM, Gardner LB (2007) Hypoxic regulation of id-1 and activation of the unfolded protein response are aberrant in neuroblastoma. J Biol Chem 282:240–248
Nicholls D, Attwell D (1990) The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11:462–468
Nilsson GE, Lutz PL (1991) Release of inhibitory neurotransmitters in response to anoxia in turtle brain. Am J Physiol 261:R32–R37
Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11:381–389
Pan C, Giraldo GS, Prentice H, Wu JY (2010a) Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress. J Biomed Sci 17:S17
Pan C, Gupta A, Prentice H, Wu JY (2010b) Protection of taurine and granulocyte colony-stimulating factor against excitotoxicity induced by glutamate in primary cortical neurons. J Biomed Sci 17:S18
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 60:115–122
Paula-Lima AC, Felice GF, Brito-Moreira J, Ferreira TS (2005) Activation of GABAA receptors by taurine and muscimol blocks the neurotoxicity of α-amyloid in rat hippocampal and cortical neurons. Neuropharmacology 49:1140–1148
Pizzo P, Pozzan T (2007) Mitochondria-endoplasmic reticulum choreography: structure and signaling dynamics. Trends Cell Biol 17:511–517
Prostko CR, Brostrom MA, Brostrom CO (1993) Reversible phosphorylation of eukaryotic initiation factor 2 alpha in response to endoplasmic reticular signaling. Mol Cell Biochem 128:255–265
Ron D (2002) Translational control in the endoplasmic reticulum stress response. J Clin Invest 110:1383–1388
Rothman SM, Olney JW (1986) Glutamate and the pathophysiology of hypoxic-ischemic brain damage. Ann Neurol 19:105–111
Schaffer SW, Azuma J, Mozaffari M (2009) Role of antioxidant activity of taurine in diabetes. Can J Physiol Pharmacol 87:91–99
Sturman JA (1993) Taurine in development. Physiol Rev 73:119–147
Szegezdi E, Logue SE, Gorman AM, Samali A (2006) Mediators of endoplasmic reticulum stress-induced apoptosis. EMBO J 7:880–885
Tadros MG, Khalifa AE, Abdel-Naim AB, Arafa HM (2005) Neuroprotective effect of taurine in 3-nitropropionic acid-induced experimental animal model of Huntington’s disease phenotype. Pharmacol Biochem Behav 82:574–582
Tajiri S, Oyadomari S, Yano S, Morioka M, Gotoh T, Hamada JI, Ushio Y, Mori M (2004) Ischemia-induced neuronal cell death is mediated by the endoplasmic reticulum stress pathway involving CHOP. Cell Death Differ 11:403–415
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 41:726–733
Takatani T, Takahashi K, Uozumi Y, Matsuda T, Ito T, Schaffer SW, Fujio Y, Azuma J (2004a) Taurine prevents the ischemia-induced apoptosis in cultured neonatal rat cardiomyocytes through Akt/caspase-9 pathway. Biochem Biophys Res Commun 316(2):484–489
Takatani T, Takahashi K, Uozumi Y, Shikata E, Yamamoto Y, Ito T, Matsuda T, Schaffer SW, Fujio Y, Azuma J (2004b) Taurine inhibits apoptosis by preventing formation of the Apaf-1/caspase-9 apoptosome. Am J Physiol Cell Physiol 287:C949–C953
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 34:169–174
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 17:5708–5717
Yoneda T, Imaizumi K, Oono K, Yui D, Gomi F, Taiichi K, 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 276:13935–13940
Yoshida H, Haze K, Yanagi H, Yura T, Mori K (1998) Identification of the cis-acting endoplasmic reticulum stress response element responsible for transcriptional induction of mammalian glucose-regulated proteins Involvement of basic leucine zipper transcription factors. J Biol Chem 273:33741–33749
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 21:872–884
Acknowledgments
This work was supported partially by grant from Department of Health, James & Esther King Biomedical Research Program, State of Florida (09KW-11).
Conflict of interest
The authors declare that they have no conflict of interests.
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Pan, C., Prentice, H., Price, A.L. et al. Beneficial effect of taurine on hypoxia- and glutamate-induced endoplasmic reticulum stress pathways in primary neuronal culture. Amino Acids 43, 845–855 (2012). https://doi.org/10.1007/s00726-011-1141-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00726-011-1141-6