Phaseic acid: an endogenous and reversible inhibitor of glutamate receptors in mouse brain

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DOIResolve DOI: https://doi.org/10.1074/jbc.M116.756429
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Name affiliation
  1. National Research Council of Canada. Human Health Therapeutics
  2. National Research Council of Canada. Aquatic and Crop Resource Development
FormatText, Article
Journal titleThe Journal of Biological Chemistry
ISSN0021-9258
1083-351X
Article numberjbc.M116.756429
Subjectphaseic acid; abscisic acid; UPLC/MS/MS; endothelial cells; choroid plexus; cerebrospinal fluid; cerebral ischemia
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 (MCAO) elicited a significant induction in (-)-PA expression in the CSF, 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 (-)-PA level in the brain reduced ischemic brain injury, while reducing (-)-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 reversible inhibiting glutamate receptors during ischemic brain injury.
Publication date
PublisherAmerican Society for Biochemistry and Molecular Biology
LanguageEnglish
Peer reviewedYes
NPARC number23001033
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Record created2016-12-01
Record modified2020-06-02
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