2. Academic Validation
  3. Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain

Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain

  • J Biol Chem. 2016 Dec 30;291(53):27007-27022. doi: 10.1074/jbc.M116.756429.
Sheng Tao Hou 1 2 3,  Susan X Jiang 2,  L Irina Zaharia 4,  Xiumei Han 4,  Chantel L Benson 4,  Jacqueline Slinn 2,  Suzanne R Abrams 4
Affiliations

Affiliations

  • 1 From the Brain Research Centre and Department of Biology, Southern University of Science and Technology, 1088 Xueyuan Boulevard, Nanshan District, Shenzhen, 518055 Guangdong Province, China, hou.st@sustc.edu.cn.
  • 2 Experimental NeuroTherapeutics, Human Health Therapeutics Portfolio, National Research Council Canada, 1200 Montreal Road, Building M54, Ottawa K1A 0R6, Ontario, Canada.
  • 3 the Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Ontario K1H 8M5, Canada.
  • 4 Aquatic and Crop Resource Development, National Research Council Canada, 110 Gymnasium Place, Saskatoon, Saskatchewan S7N 0W9, Canada, and.
PMID: 27864367 DOI: 10.1074/jbc.M116.756429
Abstract

Phaseic acid (PA) is a Phytohormone regulating important physiological functions in higher Plants. Here, we show the presence of naturally occurring (-)-PA in mouse and rat brains. (-)-PA is exclusively present in the choroid plexus and the cerebral vascular endothelial cells. Purified (-)-PA has no toxicity and protects cultured cortical neurons against glutamate toxicity through reversible inhibition of glutamate receptors. Focal occlusion of the middle cerebral artery elicited a significant induction in (-)-PA expression in the cerebrospinal fluid but not in the peripheral blood. Importantly, (-)-PA induction only occurred in the penumbra area, indicting a protective role of PA in the brain. Indeed, elevating the (-)-PA level in the brain reduced ischemic brain injury, whereas reducing the (-)-PA level using a monoclonal antibody against (-)-PA increased ischemic injury. Collectively, these studies showed for the first time that (-)-PA is an endogenous neuroprotective molecule capable of reversibly inhibiting glutamate receptors during ischemic brain injury.

Keywords

UPLC/MS/MS; abscisic acid (ABA); cerebral ischemia; choroid plexus; endothelial cells; neurochemistry; neurological disease; neuroprotection; phaseic acid; stroke.

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