Glutamate transporters in brain ischemia: to modulate or not?
Abstract
Weronika KRZYŻANOWSKA1, *, Bartosz POMIERNY1, Małgorzata FILIP1, Joanna PERA2
1Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland; 2Department of Neurology, Jagiellonian University, Medical College, Krakow, Poland
In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system xc-) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.
Keywords: glutamate; brain ischemia; excitatory amino acid transporter; cystine/glutamate antiporter; vesicular glutamate transporter; ischemic preconditioning; ceftriaxone
The work of the team is supported by National Science Centre grant No 2011/01/B/NZ4/00783 and by Ministry of Science and Higher Education: K/DSC/000793 and K/DSC/000779, Poland.
* To whom correspondence should be addressed.
E-mail weronika.krzyzanowska@uj.edu.pl
Received 2013-07-29 Accepted 2014-01-13
Keywords:
1Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland; 2Department of Neurology, Jagiellonian University, Medical College, Krakow, Poland
In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system xc-) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.
Keywords: glutamate; brain ischemia; excitatory amino acid transporter; cystine/glutamate antiporter; vesicular glutamate transporter; ischemic preconditioning; ceftriaxone
The work of the team is supported by National Science Centre grant No 2011/01/B/NZ4/00783 and by Ministry of Science and Higher Education: K/DSC/000793 and K/DSC/000779, Poland.
* To whom correspondence should be addressed.
E-mail weronika.krzyzanowska@uj.edu.pl
Received 2013-07-29 Accepted 2014-01-13