[Role of tyrosine kinase of Trk-receptors in realization of antioxidant effect of ganglioside GM1 in PC12 cells].
Ganglioside GM1 has been shown to increase viability of PC12 cells at their induction of oxidative stress by hydrogen peroxide. However, in the presence of inhibitor of tyroxine kinase Trk-receptors K-252a this GM1 effect decreases or virtually disappears. To understand mechanism of the protective effect, there was studied action of H2O2, GM1, and inhibitor K-252a on formation of reactive oxygen species (ROS). It has been shown that ganglioside GM1 decreases significantly the H2O2-induced ROS accumulation in PC12 cells; however, in the presence of inhibitory of tyrosine kinase of Trk-receptors, this GM1 effect is not revealed. It has been found that inhibitors of each of protein kinases present at the signal realization stages following the stages of activation of tyrosine kinase Trk-receptors--Erk 1/2, PI3-kinases, and PKC, decreased the GM1 ability to reduce the H2O2-induced ROS accumulation, while in the combined use of inhibitors of these three protein kinases, the GM1 effect was completely absent. Thus, the ganglioside GM1 antioxidant effect on PC12 is mediated by activation of tyrosine kinase Trk-receptors and protein kinases perceiving signal from this enzyme.
Vlasova
Iu A
IuA
Zakharova
I O
IO
Sokolova
T V
TV
Furaev
V V
VV
Rychkova
M P
MP
Avrova
N F
NF
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D026121:Indole Alkaloids / Q000494:pharmacology; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
D000975:Antioxidants; D002227:Carbazoles; D004791:Enzyme Inhibitors; D026121:Indole Alkaloids; D016877:Oxidants; D005677:G(M1) Ganglioside; C049985:staurosporine aglycone; D006861:Hydrogen Peroxide; D019869:Phosphatidylinositol 3-Kinases; D020794:Receptor Protein-Tyrosine Kinases; D011493:Protein Kinase C; D048052:Mitogen-Activated Protein Kinase 3