Modulation of Na(+)-dependent glutamate transporter of murine astrocytes by inflammatory mediators.
Sodium-dependent glutamate transporters of astrocytes have been reported to maintain extracellular concentration of glutamate below toxic level in the central nervous system and to be concerned with neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS) and Alzheimer's disease (AD). In this study, the effects of inflammatory mediators including prostaglandin (PG) E2, interleukin (IL)-1beta and IL-6 on Na(+)-dependent L-glutamate transport of astrocytes were analyzed using primary murine astrocytes. The exposure of astrocytes to PGE2 for 24 h elicited a dose-dependent increase of L-glutamate uptake. Neither IL-beta nor IL-6 alone had any effect on L-glutamate uptake. However, IL-1beta enhanced the PGE2-induced increase of L-glutamate uptake. IL-6 suppressed the increase of L-glutamate uptake induced by PGE2. Kinetic analysis of L-glutamate uptake showed that PGE2 and PGE2 with IL-1beta increased V(max) value with no significant effect on Km value for Na(+)-dependent L-glutamate uptake. IL-6 suppressed the PGE2-induced V(max) value. These results suggest that IL-1beta, IL-6 and PGE2 modulate glutamate transport of astrocytes and play a role in the pathogenesis of neurodegenerative disorders such as ALS and AD.
Department of Neurology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu 807-8555, Japan.
Kazumasa
K
Okada
Uki
U
Yamashita
Sadatoshi
S
Tsuji
D027322:Amino Acid Transport System X-AG / Q000032:analysis*; D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000378:metabolism*; D002478:Cells, Cultured; D015232:Dinoprostone / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H
D027322:Amino Acid Transport System X-AG; D007375:Interleukin-1; D015850:Interleukin-6; D018698:Glutamic Acid; D015232:Dinoprostone