α-Tocopherol at Nanomolar Concentration Protects Cortical Neurons against Oxidative Stress.

The aim of the present work is to study the mechanism of the α-tocopherol (α-T) protective action at nanomolar and micromolar concentrations against H₂O₂-induced brain cortical neuron death. The mechanism of α-T action on neurons at its nanomolar concentrations characteristic for brain extracellular space has not been practically studied yet. Preincubation with nanomolar and micromolar α-T for 18 h was found to increase the viability of cortical neurons exposed to H₂O₂; α-T effect was concentration-dependent in the nanomolar range.

GM1 ganglioside activates ERK1/2 and Akt downstream of Trk tyrosine kinase and protects PC12 cells against hydrogen peroxide toxicity.

Ganglioside GM1 at micro- and nanomolar concentrations was shown to increase the viability of pheochromocytoma PC12 cells exposed to hydrogen peroxide and diminish the accumulation of reactive oxygen species and oxidative inactivation of Na(+),K(+)-ATPase, the effects of micromolar GM1 being more pronounced than those of nanomolar GM1. These effects of GM1 were abolished by Trk receptor tyrosine kinase inhibitor and diminished by MEK1/2, phosphoinositide 3-kinase and protein kinase C inhibitors. Hydrogen peroxide activates Trk tyrosine kinase; Akt and ERK1/2 are activated downstream of this protein kinase.

α-Tocopherol at nanomolar concentration protects PC12 cells from hydrogen peroxide-induced death and modulates protein kinase activities.

The aim of this work was to compare protective and anti-apoptotic effects of α-tocopherol at nanomolar and micromolar concentrations against 0.2 mM H(2)O(2)-induced toxicity in the PC12 neuronal cell line and to reveal protein kinases that contribute to α-tocopherol protective action. The protection by 100 nM α-tocopherol against H(2)O(2)-induced PC12 cell death was pronounced if the time of pre-incubation with α-tocopherol was 3-18 h.

Protective and antioxidative effects of GM1 ganglioside in PC12 cells exposed to hydrogen peroxide are mediated by Trk tyrosine kinase.

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.