Glutamate affects the CYP1B1- and CYP2U1-mediated hydroxylation of arachidonic acid metabolism via astrocytic mGlu5 receptor. (May 2019)

• Record Type: Journal Article
• Authors: Yu, Xuming; Wu, Juan; Hu, Mingbai; Wu, Jinhua; Zhu, Quanfei; Yang, Zheqiong; Xie, Xianfei; Feng, Yu-Qi; Yue, Jiang
• Is Part Of: International journal of biochemistry & cell biology. Volume 110(2019)
• Page Start: 111
• Page End: 121
• Publication Date: 2019-05
• Subjects: AA arachidonic acid -- EETs epoxyeicosatrienoic acids -- HETEs hydroxyeicosatetraenoic acids -- CYP cytochrome P450 -- CREB cAMP response element-binding protein -- mGlu5 receptor metabotropic glutamate receptor subtype 5 -- MAPK mitogen-activated protein kinases -- MPEP 2-methyl-6-(phenylethynyl)-pyridine -- DAPI 4, 6-diamidino-2-phenylindole -- IOD integrated option density -- ChIP chromatin immunoprecipitation -- ACN Analytical grade acetonitrile -- EtOAc ethyl acetate -- BHT 2, 6-di-tert-butyl-4-methylphenol -- L-AA L(+)-ascorbicacid -- FA formic acid -- CMPI 2-chloro-1-methylpyridinium iodide -- TEA triethylamine -- DMED 2-dimethylaminoethylamine -- CSD cortical spreading depression -- LSD least significance difference; Cytochrome P450 -- Brain -- Hydroxyicosatetraenoic acid -- Glutamate; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2019.03.001
• Languages: English
• ISSNs: 1357-2725

Abstract

Highlights: Astrocytic CYP1B1 and CYP2U1 are induced by glutamate via mGlu5 receptor. Glutamate increases the CREB-mediated activation of CYP1B1 and CYP2U1 promoters. Glutamate alters CYP-mediated production of HETEs from arachidonic acid in rat brain. Abstract: The extrahepatic CYP enzymes, CYP1B1 and CYP2U1, have been predominantly found in both astrocytes and brain microvessels. We investigated the alteration in the production of hydroxyeicosatetraenoic acids (HETEs) from arachidonic acid (AA) mainly via CYP1B1 and CYP2U1 by glutamate. CYP1B1 and CYP2U1 mRNA levels were dose-dependently induced by glutamate in human U251 glioma cells and hCMEC/D3 blood-brain barrier cells. The increases in the CYP1B1 and CYP2U1 mRNA levels and the binding of CREB to CYP1B1 and CYP2U1 promoters following glutamate treatment were attenuated by mGlu5 receptor antagonist. The mRNA levels of CYP1B1 and CYP2U1 were increased in the cortex, hippocampus, and cerebellum from adult rats that received a subcutaneous injection of monosodium l -glutamate at 1, 3, 5, and 7 days of age; meanwhile, the protein levels of CYP1B1 and CYP2U1 in the astrocytes were induced by glutamate. Glutamate treatment significantly increased the production of 5-HETE, 8-HETE, 11-HETE, and 20-HETE in the cortex and cerebellum. These data suggested that the neuron-astrocyte reciprocal signaling can change the CYP-mediated AA metabolism (e.g. EETs and HETEs) in astrocytes via its specific receptor.