[Neurotoxic activity of serum and cerebrospinal fluid of amyotrophic lateral sclerosis patients against some enzymes of glutamate metabolism].
One of the hypotheses in amyotrophic lateral sclerosis (ALS) indicates on excitatory amino acids as the cause of neuronal death. Changes in their concentration in the tissues and body fluids may be the consequence of a defect in their transport, as well as abnormal activities of glutamate metabolizing enzymes. Abnormal synthesis/degradation of these enzymes and/or influence of activators/inhibitors should be taken into account. The activity of enzymes of glutamate metabolism of rat spinal cord in vitro in the presence of serum and cerebrospinal fluid (CSF) of 20 patients with ALS and 20 healthy controls was tested. In the presence of serum of the ALS patients glutaminase was significantly stimulated, instead of being inhibited; the inhibition of GABA aminotransferase, glutamate decaboxylase and aspartate aminotransferase was less evident than in the controls, glutamate dehydrogenase lost its activity more than in control conditions, the inhibition of glutamine synthetase was comparable to that when normal serum was applied. The activity of the enzymes in the presence of CSF of ALS patients was generally similar to that of normal CSF, except of glutaminase which was stimulated and GABA aminotransferase, which was inhibited stronger than in the presence of normal CSF. This study indicates, that changes in glutamate concentration in tissues and body fluids in ALS may be caused, at least partly, by abnormalities in the activity of glutamate metabolism enzymes, which are in turn induced by neurotoxic agents present in body fluids of ALS patients.
Niebroj-Dobosz
I
I
Katedra i Klinika Neurologii AM w Warszawie.
Janik
P
P
Mickielewicz
A
A
Jamrozik
Z
Z
Kwieciński
H
H
D000612:4-Aminobutyrate Transaminase / Q000378:metabolism; D000328:Adult; D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D004798:Enzymes / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*; D005260:Female; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005969:Glutamate Dehydrogenase / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009498:Neurotoxins / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
D004798:Enzymes; D009498:Neurotoxins; D005969:Glutamate Dehydrogenase; D001219:Aspartate Aminotransferases; D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D005974:Glutamate-Ammonia Ligase