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
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DOI：
10.1074/jbc.m116.756429
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发表时间：
2016-12-30
影响因子：
4.8
通讯作者：
Abrams, Suzanne R.
中科院分区：
文献类型：
--
作者：
Hou, Sheng Tao;Jiang, Susan X.;Abrams, Suzanne R.
菜豆酸（Phaseic acid，PA）是一种植物激素，在高等植物中具有重要的生理功能.在这里，我们展示了小鼠和大鼠大脑中天然存在的（-）-PA。（-）-PA仅存在于脉络丛和脑血管内皮细胞中。纯化的（-）-PA无毒性，通过可逆性抑制谷氨酸受体保护培养的皮层神经元免受谷氨酸毒性。局灶性大脑中动脉闭塞引起脑脊液中（-）-PA表达的显着诱导，但在外周血中没有。重要的是，（-）-PA诱导只发生在半影区，表明PA在脑中的保护作用。事实上，升高脑中的（-）-PA水平减少缺血性脑损伤，而使用针对（-）-PA的单克隆抗体降低（-）-PA水平增加缺血性损伤。总的来说，这些研究首次表明，（-）-PA是一种内源性神经保护分子，能够可逆地抑制缺血性脑损伤过程中的谷氨酸受体。
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.