title: Glutamate/glutamine metabolism coupling between astrocytes and glioma cells: neuroprotection and inhibition of glioma growth.
abstract: Glioma glutamate release has been shown to promote the growth of glioma cells and induce neuronal injuries from epilepsy to neuronal death. However, potential counteractions from normal astrocytes against glioma glutamate release have not been fully evaluated. In this study, we investigated the glutamate/glutamine cycling between glioma cells and astrocytes and their impact on neuronal function. Co-cultures of glioma cells with astrocytes (CGA) in direct contact were established under different mix ratio of astrocyte/glioma. Culture medium conditioned in these CGAs were sampled for HPLC measurement, for neuronal ratiometric calcium imaging, and for neuronal survival assay. We found: (1) High levels of glutaminase expression in glioma cells, but not in astrocytes, glutaminase enables glioma cells to release large amount of glutamate in the presence of glutamine. (2) Glutamate levels in CGAs were directly determined by the astrocyte/glioma ratios, indicating a balance between glioma glutamate release and astrocyte glutamate uptake. (3) Culture media from CGAs of higher glioma/astrocyte ratios induced stronger neuronal Ca(2+) response and more severe neuronal death. (4) Co-culturing with astrocytes significantly reduced the growth rate of glioma cells. These results indicate that normal astrocytes in the brain play pivotal roles in glioma growth inhibition and in reducing neuronal injuries from glioma glutamate release. However, as tumor growth, the protective role of astrocytes gradually succumb to glioma cells.
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, China.
authors.forename: Pei-Sen
authors.initials: PS
authors.lastname: Yao
authors.affiliation: The First Clinical Medical College of Fujian Medical University, Fuzhou, China; Department of Neurosurgery, The First Affiliated Hospital of Fujian Medical University, Fuzhou, China. Electronic address: kdzy99988@163.com.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Kang
authors.affiliation: Center for Neuroscience Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Ru-Ying
authors.initials: RY
authors.lastname: Lin
authors.affiliation: Department of Neurology, Fujian Institute of Geriatrics, Union Hospital of Fujian, Fuzhou, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Ye
authors.affiliation: Center for Neuroscience Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Center for Neuroscience Research, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China; Department of Neurology, University of Washington School of Medicine, Seattle, WA, USA. Electronic address: zcye@uw.edu.
authors.forename: Zu-Cheng
authors.initials: ZC
authors.lastname: Ye
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism* / Q000473:pathology*; D002450:Cell Communication; D049109:Cell Proliferation; D002470:Cell Survival; D002478:Cells, Cultured; D005910:Glioma / Q000378:metabolism* / Q000473:pathology*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness
chemical_list: D005973:Glutamine; D018698:Glutamic Acid
keywords: Astrocytes; Glioma; Glutamate; Glutamine