[Effects of oxidative stress inducers, neurotoxins, and ganglioside GM1 on Na+, K+-ATPase in PC12 and brain synaptosomes].
To elucidate mechanism of ganglioside neuroprotection, it is important to study their metabolic effects, specifically of action on Na+, K+ -ATPase. It has been shown that under effect of oxidative stress inductors and neurotoxins an oxidative inactivation of this enzyme takes place in PC12 cells and brain cortex synaptosomes, this inactivation being able to be prevented or decreased by ganglioside GM1. Thus, for instance, 24 h after action of 1 mM H2O2, activity of Na+, K+ -ATPase in PC12 cells decreased more than twice. However, in the case of preincubation of the cells with ganglioside GM1 prior to the H2O2 action this enzyme activity did not differ statistically significantly from control. Ganglioside GM1 also was able to increase significantly the enzyme activity decreased by action on the PC12 cells of amyloid beta-peptide (AP) causing lesion of neurons in Alzheimer's disease and at low H202 concentrations. Experiments on brain cortex synaptosomes have established that not only antioxidants--alpha-tocopherol and superoxide dismutase--but also ganglioside GM1 prevent the glutamateproduced Na+, K+ -ATPase oxidative inactivation. The obtained data agree with a suggestion that the ganglioside neuroprotective effect at action on nerve cells of such toxins as Abeta, glutamate or reactive oxygen species is due to their ability to inhibit the free-radical reactions.
Zakharova
I O
IO
Sokolova
T V
TV
Furaev
V V
VV
Rychkova
M P
MP
Avrova
N F
NF
D016229:Amyloid beta-Peptides / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D004789:Enzyme Activation; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000494:pharmacology; D013574:Synaptosomes / Q000187:drug effects* / Q000378:metabolism; D024502:alpha-Tocopherol / Q000494:pharmacology
D016229:Amyloid beta-Peptides; D000975:Antioxidants; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D005677:G(M1) Ganglioside; D018698:Glutamic Acid; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000254:Sodium-Potassium-Exchanging ATPase; D024502:alpha-Tocopherol