title: Increased glutamine synthetase but normal EAAT2 expression in platelets of ALS patients.
abstract: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease and glutamate excitotoxicity has been implicated in its pathogenesis. Platelets contain a glutamate uptake system and express components of the glutamate-glutamine cycle, such as the predominant glial excitatory amino acid transporter 2 (EAAT2). In several neurological diseases platelets have proven to be systemic markers for the disease. We compared properties of key components of the glutamate-glutamine cycle in blood platelets of ALS patients and healthy controls. Platelets were analyzed for (3)H-glutamate uptake in the presence or absence of thrombin and for EAAT2 and glutamine synthetase protein expression by Western blotting. Platelets of ALS patients showed a 37% increase in expression of glutamine synthetase, but normal expression of glutamate transporter EAAT2. Glutamate uptake in resting or thrombin-stimulated platelets did not differ significantly between platelets from ALS patients and controls. Thrombin-stimulation resulted in about a seven-fold increase in glutamate uptake. Our data suggest that glutamine synthetase may be a peripheral marker of ALS and encourage further investigation into the role of this enzyme in ALS.
authors.affiliation: Rudolf Magnus Institute of Neuroscience, Department of Pharmacology and Anatomy, University Medical Center, Utrecht, The Netherlands.
authors.forename: I W M
authors.initials: IW
authors.lastname: Bos
authors.forename: G
authors.initials: G
authors.lastname: Hoogland
authors.forename: C F
authors.initials: CF
authors.lastname: Meine Jansen
authors.forename: G van
authors.initials: Gv
authors.lastname: Willigen
authors.forename: H A
authors.initials: HA
authors.lastname: Spierenburg
authors.forename: L H
authors.initials: LH
authors.lastname: van den Berg
authors.forename: P N E
authors.initials: PN
authors.lastname: de Graan
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D016022:Case-Control Studies; D027342:Excitatory Amino Acid Transporter 2 / Q000097:blood*; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged
chemical_list: D027342:Excitatory Amino Acid Transporter 2; D005974:Glutamate-Ammonia Ligase