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 Canada. Human Health Therapeutics
  2. National Research Council Canada. Aquatic and Crop Resource Development
FormatText
TypeArticle
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 modified2020-03-16
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