EFFECTS OF RADICAL OXYGEN SPECIES AND NO: FORMATION OF INTRACELLULAR HYPOXIA AND ACTIVATION OF MATRIX METALLOPROTEINASES IN TUMOR TISSUES

Burlaka A.P.*1, Sidorik E.P.2, Ganusevich І.І.3, Osinsky S.P.1

Summary. Aim: To establish the association between the radical oxygen species (ROS) and NO levels in the tumor cells mitochondria, between cell hypoxia development and activation of matrix metalloproteinases–2 and -9. Materials and Methods: Electron paramagnetic resonance (EPR) at room temperature and at the temperature of liquid nitrogen (77° K), spin traps technology, enzymography in polyacrylamide gel were applied. Results: Redox-centers in the respiration cascade of mitochondria have been revealed, multiple oxidative damage of which in breast and liver cancer tissues of experimental animals as well as in tumor tissue from patients with gastric cancer promote the development of cell hypoxia. Involvement of ROS and NO in activation of latent forms of matrix metalloproteinases in gastric tumor tissues has been shown. Conclusion: We hypothesize that superoxide radical-anions participate in development of cell hypoxia in tumors and surrounding normal tissues inducing activation of latent forms of matrix metalloproteinases.

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