2022
Volume 22, Number 3/4, pp. 49-51
Nitric oxide-induced cellular stress
J. Bator, J. Varga and J. Szeberenyi
Department of Medical Biology and Central Electron Microscopic Laboratory, University of Pecs Medical School, Pecs, Hungary
Nitric oxide is a mediator of a diverse array of inter- and intracellular signal transduction processes. Nitric oxide exerts its effects via multiple mechanisms: it covalently modifies various target proteins (nitrosylation), thereby changing their activities; it binds to heavy-metal ions that are components of protein complexes; and it activates the cGMP pathway. Higher concentrations of nitric oxide cause nitrosative stress, leading to cell death. We used sodium nitroprusside as a nitric oxide donor to investigate the signaling events of nitrosative stress. Cytotoxic concentrations of sodium nitroprusside activated several pro-apoptotic mechanisms (stimulation of stress kinase pathways mediated by JNK and p38MAPK, phosphorylation and stabilization of p53 protein, and activation of caspases) and inhibited Akt-mediated anti-apoptotic signaling and expression of the Bcl2 protein. Simultaneously, stimulation of the pro-survival ERK pathway was also observed, providing a certain degree of protection. Surprisingly, pretreatment with a lower dose of the nitric oxide donor effectively protected cells from the toxic effect of the higher dose treatment. It was concluded that nitric oxide modulates various signaling pathways. The fate of the cell is determined by the collective impact of these pathways on cell survival.
Keywords: apoptosis, nitrosative stress, PC12 cell line, sodium nitroprusside