title: Exposure to high glutamate concentration activates aerobic glycolysis but inhibits ATP-linked respiration in cultured cortical astrocytes.
abstract: Astrocytes play a key role in removing the synaptically released glutamate from the extracellular space and maintaining the glutamate below neurotoxic level in the brain. However, high concentration of glutamate leads to toxicity in astrocytes, and the underlying mechanisms are unclear. The purpose of this study was to investigate whether energy metabolism disorder, especially impairment of mitochondrial respiration, is involved in the glutamate-induced gliotoxicity. Exposure to 10-mM glutamate for 48 h stimulated glycolysis and respiration in astrocytes. However, the increased oxygen consumption was used for proton leak and non-mitochondrial respiration, but not for oxidative phosphorylation and ATP generation. When the exposure time extended to 72 h, glycolysis was still activated for ATP generation, but the mitochondrial ATP-linked respiration of astrocytes was reduced. The glutamate-induced astrocyte damage can be mimicked by the non-metabolized substrate d-aspartate but reversed by the non-selective glutamate transporter inhibitor TBOA. In addition, the glutamate toxicity can be partially reversed by vitamin E. These findings demonstrate that changes of bioenergetic profile occur in cultured cortical astrocytes exposed to high concentration of glutamate and highlight the role of mitochondria respiration in glutamate-induced gliotoxicity in cortical astrocytes.
authors: Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, College of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors: Yao
authors: Y
authors: Shen
authors: Yueyang
authors: Y
authors: Tian
authors: Xiaojie
authors: X
authors: Shi
authors: Jianbo
authors: J
authors: Yang
authors: Li
authors: L
authors: Ouyang
authors: Jieqiong
authors: J
authors: Gao
authors: Jianxin
authors: J
authors: Lu
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000332:Aerobiosis; D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D019069:Cell Respiration / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology*; D004734:Energy Metabolism / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D006019:Glycolysis; D008928:Mitochondria / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D061251:Primary Cell Culture; D017207:Rats, Sprague-Dawley; D014810:Vitamin E / Q000378:metabolism
chemical_list: C120673:benzyloxyaspartate; D014810:Vitamin E; D001224:Aspartic Acid; D018698:Glutamic Acid; D000255:Adenosine Triphosphate
keywords: astrocyte; gliotoxicity; glutamate; glycolysis; mitochondria respiration