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Expression of glucose transporter GLUT3 by endotoxin in cultured rat astrocytes: the role of nitric oxide
Author(s) -
Cidad Pilar,
GarciaNogales Paula,
Almeida Angeles,
Bolaños Juan P.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00523.x
Subject(s) - glut3 , glucose transporter , glut1 , nitric oxide synthase , glucose transporter type 1 , glucose uptake , nitric oxide , medicine , incubation , endocrinology , astrocyte , biology , lipopolysaccharide , glutamate receptor , trypan blue , biochemistry , apoptosis , insulin , receptor , central nervous system
The induction of nitric oxide (NO) synthase in astrocytes by endotoxin and/or cytokine treatment is associated with increased glucose consumption and glycolysis, but the mechanism whereby this phenomenon occurs remains obscure. In this work, we have addressed this issue and found that incubation of cultured rat astrocytes with lipopolysaccharide (LPS; 1 µg/mL) for 24 h increased the level of constitutively expressed GLUT1 glucose transporter mRNA, and triggered GLUT3 mRNA expression, which was absent in normal astrocytes. The occurrence of GLUT3 protein after LPS treatment was corroborated by western blotting and immunocytochemistry. A 4‐h incubation of astrocytes in the absence of glucose, or under an oxygen‐poor (3%) atmosphere also resulted in GLUT3 mRNA overexpression. Experiments performed with 2‐deoxy‐ d ‐[U‐ 14 C]glucose (at 0.1 m m of d ‐glucose) confirmed that LPS (0.1–10 µg/mL) dose‐dependently increased the rate of glucose uptake (by a factor of 1.6 at 1 µg/mL of LPS), which was paralleled with the increase in NO synthesis. Furthermore, blockade of NO synthase with 2‐amino‐5,6‐dihydro‐6‐methyl‐(4 H )‐1,3‐thiazine (AMT; 50 µ m ) partially (by 45%) prevented the LPS‐mediated increase in glucose uptake. Finally, incubation of astrocytes with the NO donor 1‐[2‐(2‐aminoethyl)‐ N ‐(2‐ammonioethyl)amino]diazen‐1‐ium‐1,2‐diolate (DETA; 100 µ m ) increased by a factor of 1.4 the rate of glucose uptake. We conclude that the increase in GLUT3‐driven glucose uptake in astrocytes would have a neuroprotective role under conditions in which NO formation is combined with hypoglycaemia, such as in brain ischemia.