Protective and Antioxidative Effects of GM1 Ganglioside in PC12 Cells Exposed to Hydrogen Peroxide are Mediated by Trk Tyrosine Kinase

• Published in: Neurochemical research 2010, Vol.35 (1), p.85-98
• Main Authors: Avrova, Natalia F., Sokolova, Tatyana V., Vlasova, Yulia A., Zakharova, Irina O., Furaev, Victor V., Rychkova, Maria P.
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; Biochemistry; Biomedical and Life Sciences; Biomedicine; Calcium - metabolism; Cell Biology; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors; G(M1) Ganglioside - metabolism; Hydrogen Peroxide - pharmacology; L-Lactate Dehydrogenase - metabolism; Neurochemistry; Neurology; Neurosciences; Original Paper; PC12 Cells; Protein Kinase Inhibitors - pharmacology; Rats; Receptor, trkA - metabolism; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 0364-3190; 1573-6903
• DOI: 10.1007/s11064-009-0033-6

GM1 ganglioside was found to increase the survival of PC12 cells exposed to H 2 O 2 , its action was blocked by Trk tyrosine kinase inhibitor K-252a. Thus, the inhibition of H 2 O 2 cytotoxic action by GM1 constituted 52.8 ± 4.3%, but in the presence of 1.0 μM K-252a it was only 11.7 ± 10.8%, i.e. the effect of GM1 became insignificant. Exposure to GM1 markedly reduced the increased accumulation of reactive oxygen species (ROS) and diminished the inactivation of Na + ,K + -ATPase induced in PC12 cells by H 2 O 2 , but in the presence of K-252a GM1 did not change these metabolic parameters. The inhibitors of extracellular signal-regulated protein kinase, phosphatidyl inositol 3-kinase and protein kinase C decreased the effects of GM1. A combination of these protein kinase inhibitors reduced inhibition of H 2 O 2 cytotoxic action by GM1 to the larger extent than each of the inhibitors and practically abolished the ability of GM1 to decrease H 2 O 2 -induced ROS accumulation. The protective and antioxidative effects of GM1 in PC12 cells exposed to H 2 O 2 appear to be mediated by activation of Trk receptor tyrosine kinase and the protein kinases downstream from this enzyme.