Phaseic Acid, an Endogenous and Reversible Inhibitor of Glutamate Receptors in Mouse Brain
| Autor: | Chantel L. Benson, Xiumei Han, Suzanne R. Abrams, L. Irina Zaharia, Sheng T. Hou, Susan X. Jiang, Jacqueline Slinn |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Glutamic Acid UPLC/MS/MS Endogeny Biology Pharmacology Biochemistry Neuroprotection cerebrospinal fluid cerebral ischemia Brain Ischemia Rats Sprague-Dawley abscisic acid Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cerebrospinal fluid Neurobiology Animals phaseic acid Molecular Biology Cells Cultured choroid plexus Penumbra Glutamate receptor Brain Infarction Middle Cerebral Artery Cell Biology Anatomy endothelial cells Rats Mice Inbred C57BL Neuroprotective Agents 030104 developmental biology Phaseic acid Receptors Glutamate chemistry Toxicity Choroid plexus Sesquiterpenes 030217 neurology & neurosurgery |
| Zdroj: | Journal of Biological Chemistry. 291:27007-27022 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m116.756429 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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