Modification of Redox Processes in C6 Glioma Cells by 2-Hexadeсenal, the Product of Sphingolipid Destruction

Abstract—2-Hexadecenal is an unsaturated aldehyde that is formed during the free radical destruction of sphingolipids under oxidative stress and exhibits biological activity by inhibiting proliferation and inducing apoptosis. The results of studying the modifying effect of this aldehyde on the redox processes that occur in rat C6 glioma cells are presented. It has been shown that cultivation of cells with 2-hexadecenal (at concentrations from 3.5 to 35 μmol/L) leads to a significant increase in the yield of menadione-induced superoxide anion radicals; and at higher concentrations, to its decrease. It has been revealed that under the action of 2-hexadecenal on cells, the additional production of ${\text{O}}_2^{\cdot -}$ is completely suppressed in the presence of inhibitors of stress-activated MAP kinases involved in apoptosis triggering, such as JNK, p38, and ERK1/2. The modifying effects of 2-hexadecenal begin to occur at the early stages of its interaction with cells, which is manifested in the increased production of superoxide anion radicals by mitochondria and a decrease in the intracellular level of reduced glutathione. It has been suggested that the modification of the redox state of C6 cells occurs at the initial stage of the intracellular signaling process, in which 2-hexadecenal plays the role of a signaling molecule.