Abstract
Taurine, as a free amino acid, is found at high levels in many tissues including brain, heart and skeletal muscle and is known to demonstrate neuroprotective effects in a range of disease conditions including stroke and neurodegenerative disease. Using in vitro culture systems we have demonstrated that taurine can elicit protection against endoplasmic reticulum stress (ER stress) from glutamate excitotoxicity or from excessive reactive oxygen species in PC12 cells or rat neuronal cultures. In our current investigation we hypothesized that taurine treatment after stroke in the rat middle cerebral artery occlusion (MCAO) model would render protection against ER stress processes as reflected in decreased levels of expression of ER stress pathway components. We demonstrated that taurine elicited high level protection and inhibited both ATF-6 and IRE-1 ER stress pathway components. As ischemic stroke has a complex pathology it is likely that certain combination treatment approaches targeting multiple disease mechanisms may have excellent potential for efficacy. We have previously employed the partial NMDA antagonist DETC-MeSO to render protection against in vivo ischemic stroke using a rat cerebral ischemia model. Here we tested administration of subcutaneous administration of 0.56 mg/kg DETC-MeSO or 40 mg/kg of taurine separately or as combined treatment after a 120 min cerebral ischemia in the rat MCAO model. Neither drug alone demonstrated protection at the low doses employed. Remarkably however the combination of low dose DETC-MeSO plus low dose taurine conferred a diminished infarct size and an enhanced Neuroscore (reflecting decreased neurological deficit). Analysis of ER stress markers pPERK, peIF-2-alpha and cleaved ATF-6 all showed decreased expression demonstrating that all 3 ER stress pathways were inhibited concurrent with a synergistic protective effect by the post-stroke administration of this DETC-MeSO-taurine combination treatment.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Abbreviations
- DETC-MeSO:
-
S-methyl N,N-diethylthiocarbamate sulfoxide
- ER stress:
-
ER stress
- MCAO:
-
Middle cerebral artery occlusion
References
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(6):1304–1308
Broughton BR, Reutens DC, Sobey CG (2009) Apoptotic mechanisms after cerebral ischemia. Stroke 40(5):e331–e339
Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171–182
DeGracia DJ, Montie HL (2004) Cerebral ischemia and the unfolded protein response. J Neurochem 91(1):1–8
Gharibani PM, Modi J, Pan C, Menzie J, Ma Z, Chen PC, Tao R, Prentice H, Wu JY (2013) 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. Adv Exp Med Biol 776:241–258
Gharibani PM, Modi J, Menzie J, Genova R, Ma Z, Tao R, Prentice H, Wu JY (2014) Mode of action of S-methyl-N, Nhypdiethylthiocarbamate (DETC-MeSO) as a novel therpy for stroke in a rat model. Mol Neurobiol 50(2):655–672
Gharibani P, Modi J, Menzie J, Alexandrescu A, Ma Z, Tao R, Prentice H, Wu JY (2015) Comparison between single and combined post-treatment with S-Methyl-N,N-diethylthiolcarbamate sulfoxide and taurine following transient focal cerebral ischemia in rat brain. Neuroscience 300:460–473
Go AS et al (2014) Heart disease and stroke statistics—2014 update: a report from the American Heart Association. Circulation 129(3):e28–e292
Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6(5):1099–1108
Kiewert C, Mdzinarishvili A, Hartmann J, Bickel U, Klein J (2010) Metabolic and transmitter changes in core and penumbra after middle cerebral artery occlusion in mice. Brain Res 1312:101–107
Kim I, Xu W, Reed JC (2008) Cell death and endoplasmic reticulum stress: disease relevance and therapeutic opportunities. Nat Rev Drug Discov 7(12):1013–1030
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(1):84–89
Kumari N, Prentice H, Wu JY (2013) Taurine and its neuroprotective role. Adv Exp Med Biol 775:19–27
Li F, Omae T, Fisher M (1999) Spontaneous hyperthermia and its mechanism in the intraluminal suture middle cerebral artery occlusion model of rats. Stroke 30(11):2464–2470; discussion 2470–1
Longa EZ. Weinstein PR, Carlson S, Cummins R (1989) Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke 20(1):84–91
McCollum M, Ma Z, Cohen E, Leon R, Tao R, Wu JY, 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(2–3):410–419
Menzie J, Pan C, Prentice H, Wu JY (2014) Taurine and central nervous system disorders. Amino Acids 46(1):31–46
Modi JP, Gharibani PM, Ma Z, Tao R, Menzie J, Prentice H, Wu JY (2014) Protective mechanism of sulindac in an animal model of ischemic stroke. Brain Res 1576:91–99
Mohammad-Gharibani P, Modi J, Menzie J, Genova R, Ma Z, Tao R, Prentice H, Wu JY (2014) Mode of action of S-methyl-N, N-diethylthiocarbamate sulfoxide (DETC-MeSO) as a novel therapy for stroke in a rat model. Mol Neurobiol 50(2):655–672
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(6765):98–103
Nicholls D, Attwell D (1990) The release and uptake of excitatory amino acids. Trends Pharmacol Sci 11(11):462–468
Oja SS, Saransaari P (1996) Taurine as osmoregulator and neuromodulator in the brain. Metab Brain Dis 11(2):153–164
Okamoto K, Kimura H, Sakai Y (1983) Taurine-induced increase of the Cl-conductance of cerebellar Purkinje cell dendrites in vitro. Brain Res 259(2):319–323
Oyadomari S, Mori M (2004) Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ 11(4):381–389
Pan C, Prentice H, Price AL, Wu JY (2012) Beneficial effect of taurine on hypoxia- and glutamate-induced endoplasmic reticulum stress pathways in primary neuronal culture. Amino Acids 43(2):845–855
Reddy RK, Mao C, Baumeister P, Austin RC, Kaufman RJ, Lee AS (2003) Endoplasmic reticulum chaperone protein GRP78 protects cells from apoptosis induced by topoisomerase inhibitors: role of ATP binding site in suppression of caspase-7 activation. J Biol Chem 278(23):20915–20924
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(5):1419–1429
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(50):33741–33749
Acknowledgements
This work was supported by grant 09KW-11, Department of Health, State of Florida.
Author information
Authors and Affiliations
Corresponding authors
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Science+Business Media B.V.
About this paper
Cite this paper
Prentice, H. et al. (2017). Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model. In: Lee, DH., Schaffer, S.W., Park, E., Kim, H.W. (eds) Taurine 10. Advances in Experimental Medicine and Biology, vol 975. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-1079-2_17
Download citation
DOI: https://doi.org/10.1007/978-94-024-1079-2_17
Publisher Name: Springer, Dordrecht
Print ISBN: 978-94-024-1077-8
Online ISBN: 978-94-024-1079-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)