Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model

Howard Prentice, Payam Mohammadgharibani, Zhiyuan Ma, Anamaria Alexandrescu, Rafaella Genova, Po Chih Chen, Jigar Modi, Janet Menzie, Chunliu Pan, Rui Tao, Jang Yen Wu

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)193-205
Number of pages13
JournalAdvances in experimental medicine and biology
Volume975
DOIs
StatePublished - Jan 1 2017
Externally publishedYes

Fingerprint

Taurine
Endoplasmic Reticulum Stress
Rats
Stroke
Middle Cerebral Artery Infarction
Brain Ischemia
Neurodegenerative diseases
PC12 Cells
Neuroprotective Agents
Pathology
N-Methylaspartate
Neurodegenerative Diseases
Muscle
Glutamic Acid
Reactive Oxygen Species
Brain
Myocardium
Skeletal Muscle
Tissue
Amino Acids

Keywords

  • Apoptosis
  • Endoplasmic reticulum stress
  • Stroke
  • Taurine
  • • DETC-MeSO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model. / Prentice, Howard; Mohammadgharibani, Payam; Ma, Zhiyuan; Alexandrescu, Anamaria; Genova, Rafaella; Chen, Po Chih; Modi, Jigar; Menzie, Janet; Pan, Chunliu; Tao, Rui; Wu, Jang Yen.

In: Advances in experimental medicine and biology, Vol. 975, 01.01.2017, p. 193-205.

Research output: Contribution to journalArticle

Prentice, Howard ; Mohammadgharibani, Payam ; Ma, Zhiyuan ; Alexandrescu, Anamaria ; Genova, Rafaella ; Chen, Po Chih ; Modi, Jigar ; Menzie, Janet ; Pan, Chunliu ; Tao, Rui ; Wu, Jang Yen. / Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model. In: Advances in experimental medicine and biology. 2017 ; Vol. 975. pp. 193-205.
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AU - Genova, Rafaella

AU - Chen, Po Chih

AU - Modi, Jigar

AU - Menzie, Janet

AU - Pan, Chunliu

AU - Tao, Rui

AU - Wu, Jang Yen

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