Inhibition of glutamate-induced intensification of free radical reactions by gangliosides: possible role in their protective effect in rat cerebellar granule cells and brain synaptosomes.
The neurotoxic effect of exposure of rat cerebellar granule cells to glutamate (100 microM) is to a large extent prevented by incubation of neurons not only with micromolar, but even with nanomolar concentrations of gangliosides GM1, GD1b, and GT1b. GM1 was also shown to decrease significantly the per cent of dead neurons in culture after induction of lipid peroxidation. Exposure to glutamate was found to cause a significant decrease of the activity of Na+, K+-ATP-ase in rat brain cortex synaptosomes, but superoxide dismutase, alpha-tocopherol, or 10-100 nM GM1 practically prevented its action. Other data showing the ability of gangliosides to inhibit the intensification of free radical reactions by glutamate (based on the estimation of methemoglobin formation, SH group content, etc.) have been obtained. The results suggest that gangliosides are able to decrease the glutamate-induced activation of free radical reactions in nerve cells. This effect appears to contribute to their protective action against glutamate neurotoxicity.
Avrova
N F
NF
Department of Comparative Neurochemistry, Institute of Evolutionary Physiology and Biochemistry of Russian Academy of Sciences, Saint-Petersburg. avrova@ief.spb.su
Victorov
I V
IV
Tyurin
V A
VA
Zakharova
I O
IO
Sokolova
T V
TV
Andreeva
N A
NA
Stelmaschuk
E V
EV
Tyurina
Y Y
YY
Gonchar
V S
VS
D000818:Animals; D001205:Ascorbic Acid / Q000378:metabolism; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003594:Cytoplasmic Granules / Q000187:drug effects* / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000502:physiology*; D018698:Glutamic Acid / Q000633:toxicity*; D015227:Lipid Peroxidation; D009569:Nitric Oxide; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology
D017382:Reactive Oxygen Species; D013438:Sulfhydryl Compounds; D014810:Vitamin E; D009569:Nitric Oxide; D005677:G(M1) Ganglioside; D018698:Glutamic Acid; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D001205:Ascorbic Acid