The Effect of S-Nitrosoglutathione on the Amount and Activity of Erythroid Nuclear Factor Nrf2 in Human Hepatocellular Carcinoma Cells

S-nitrosoglutathione (GSNO) is an endogenous donor of nitric oxide (NO), which, at the same time, can act both as a signaling molecule and a toxic agent, forming active forms of nitrogen. The purpose of this work was to study the mechanism of NO participation in the regulation of erythroid nuclear factor 2 (Nrf2) functioning, which is a redox-sensitive transcription factor. It was shown that when GSNO was exposed to human hepatocellular carcinoma cells (HepG2), the level of intracellular NO increased dose-dependently during incubation for 24 and 72 hours. The maximum increase of NO level at 100 mM concentration led to decrease of the amount of non-protein SH groups, to maximum increase of 3-nitrothyrosine and bityrosine levels, which contributed to the decline of cell viability. The NO donor — S-nitrosoglutation activated Nrf2 during exposure for 24 hours, most likely due to nitrosylation of Keap1 protein, and at 72 hours not only activated Nrf2, but also led to an increase in its amount. This process was carried out through NO-cGMP signaling pathway. Activation of Nrf2 is a key factor in protecting cells from the toxic effects of nitrosative stress products.