The cystine-glutamate exchanger (xCT, Slc7a11) is expressed in significant concentrations in a subpopulation of astrocytes in the mouse brain

Autor: Ann Massie, Virgine Veronique Follin-Arbelet, Yun Zhou, Sigrid Ottestad-Hansen, Hideyo Sato, Qiu Xiang Hu, Niels C. Danbolt, Eduard Bentea
Přispěvatelé: Faculty of Sciences and Bioengineering Sciences, Pharmaceutical and Pharmacological Sciences, Faculty of Medicine and Pharmacy
Rok vydání: 2018
Předmět:
0301 basic medicine
Male
Astrocytes/cytology
Amino Acid Transport System y+
glia
Excitatory Amino Acid Transporter 2/metabolism
Central nervous system
Blotting
Western
Excitotoxicity
Microfilament Proteins/metabolism
Biology
SLC7A11
medicine.disease_cause
astrocyte heterogeneity
tanycytes
03 medical and health sciences
Cellular and Molecular Neuroscience
Amino Acid Transport System y+/genetics
0302 clinical medicine
Calcium-Binding Proteins/metabolism
Glutamine synthetase
Excitatory Amino Acid Transporter 3/metabolism
medicine
Animals
Circumventricular organs
Mice
Knockout
Microglia
Calcium-Binding Proteins
Microfilament Proteins
Glutamate receptor
Brain
system xc−
Immunohistochemistry
Cell biology
Mice
Inbred C57BL
030104 developmental biology
medicine.anatomical_structure
Excitatory Amino Acid Transporter 3
Neurology
Excitatory Amino Acid Transporter 2
Brain/cytology
Astrocytes
biology.protein
Female
glutamate transporter
030217 neurology & neurosurgery
Astrocyte
ISSN: 0894-1491
Popis: The cystine-glutamate exchanger (xCT) promotes glutathione synthesis by catalyzing cystine uptake and glutamate release. The released glutamate may modulate normal neural signaling and contribute to excitotoxicity in pathological situations. Uncertainty, however, remains as neither the expression levels nor the distribution of xCT have been unambiguously determined. In fact, xCT has been reported in astrocytes, neurons, oligodendrocytes and microglia, but most of the information derives from cell cultures. Here, we show by immunohistochemistry and by Western blotting that xCT is widely expressed in the central nervous system of both sexes. The labeling specificity was validated using tissue from xCT knockout mice as controls. Astrocytes were selectively labeled, but showed greatly varying labeling intensities. This astroglial heterogeneity resulted in an astrocyte domain-like labeling pattern. Strong xCT labeling was also found in the leptomeninges, along some blood vessels, in selected circumventricular organs and in a subpopulation of tanycytes residing the lateral walls of the ventral third ventricle. Neurons, oligodendrocytes and resting microglia, as well as reactive microglia induced by glutamine synthetase deficiency, were unlabeled. The concentration of xCT protein in hippocampus was compared with that of the EAAT3 glutamate transporter by immunoblotting using a chimeric xCT-EAAT3 protein to normalize xCT and EAAT3 labeling intensities. The immunoblots suggested an xCT/EAAT3 ratio close to one (0.75 ± 0.07; average ± SEM; n = 4) in adult C57BL6 mice. CONCLUSIONS: xCT is present in select blood/brain/CSF interface areas and in an astrocyte subpopulation, in sufficient quantities to support the notion that system xc- provides physiologically relevant transport activity.
Databáze: OpenAIRE
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