title: Modulation of astrocytic glutamine synthetase expression and cell viability by histamine in cultured cortical astrocytes exposed to OGD insults.
abstract: Histamine, a neurotransmitter or neuromodulator has been demonstrated to be neuroprotective in cerebral ischemia. However, few reports concern its function on astrocytes during cerebral ischemia. The purpose of this study was to investigate the effects of histamine on astrocytic cell damage and glutamate signaling, especially on glutamine synthetase (GS) expression in primary cultured cortical astrocytes exposed to oxygen-glucose deprivation (OGD) insult. OGD for 6h caused a severe damage of astrocytic mitochondrial function, and decreased GS expression and then increased the extracellular glutamate level. Pretreatment with histamine significantly prevented the cell damage and rescued the expression of GS in a concentration-dependent manner. The protective effect of histamine on astrocytic cell damage could be partly reversed either by H1 receptor antagonist pyrilamine or H2 receptor antagonist cimetidine. However, the regulatory effect of histamine on GS expression was antagonized only by pyrilamine. In addition, bisindolylmaleimide II, a broad-spectrum inhibitor of PKC, reversed the regulatory action of histamine on GS expression. These results indicate that histamine can effectively protect against OGD-induced cell damage in astrocytes through H1 and H2 receptors, and its regulatory effect on astrocytic GS expression may be due to the activation of H1 receptor and PKC pathway. Histamine may be an endogenous protective factor and calls for its further study as a regulator of astrocyte function during ischemic stroke.
authors.affiliation: Zhejiang Provincial Key Laboratory for Model Organisms, Key Laboratory of Laboratory Medicine, Ministry of Education, School of Life Sciences, Wenzhou Medical College, Wenzhou 325035, PR China.
authors.forename: Xiao-Fen
authors.initials: XF
authors.lastname: Wang
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hu
authors.forename: Hai-Jing
authors.initials: HJ
authors.lastname: Yan
authors.forename: Li
authors.initials: L
authors.lastname: Tan
authors.forename: Jie-Qiong
authors.initials: JQ
authors.lastname: Gao
authors.forename: Yue-Yang
authors.initials: YY
authors.lastname: Tian
authors.forename: Xiao-Jie
authors.initials: XJ
authors.lastname: Shi
authors.forename: Wei-Wei
authors.initials: WW
authors.lastname: Hou
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yao
authors.initials: Y
authors.lastname: Shen
authors.forename: Zhong
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006632:Histamine; D005974:Glutamate-Ammonia Ligase; D005947:Glucose; D010100:Oxygen
keywords: Astrocyte; Glutamate; Glutamine synthetase; Histamine; Protein kinase C