Redox-dependent mechanisms of apoptosis dysregulation in tumor cells under hypoxia

According to modern views formation of hypoxia during tumor progression is accompanied by generation of reactive oxygen species, which act as modulators of apoptosis, and formation of oxidative stress. Glutathione system plays an important role in the maintenance of cellular redox status by means of glutathionylation of ion transporting protein followed by regulation of intracellular signaling. The research aim was to show the role of changes in the redox status of P19 tumor cells in dysregulation of apoptosis during hypoxia. Material and methods. P19 EC cells (mouse embryonal carcinoma) cultured under normoxic and hypoxic conditions served the research material. Assessment of apoptosis, intracellular concentration of reactive oxygen species and calcium ions was performed by flow cytometry. The glutathione system parameters were determined by spectrophotometric assay. Results and discussion. It is shown that under conditions of hypoxia in P19 tumor cells increased production of active oxygen species, mixed disulfides between protein and glutathione and decreased concentration of reduced glutathione, accompanied by formation of oxidative stress and growth of intracellular calcium ion concentration. These changes have augmented the number of cells which undergo apoptosis by mitochondrial pathway.

Orlov D.S. – postgraduate student of the chair for biochemistry and molecular biology with the course of clinical laboratory diagnostics, e-mail: DOC_esperanzo@mail.ru

Ryazantseva N.V. – doctor of medical sciences, leading researcher of laboratory of bioluminescent biotechnology, professor of the chair for biological chemistry with courses of medical, pharmaceutical and toxicological chemistry, e-mail: nv_ryazan@mail.ru

Stepovaya E.A. – doctor of medical sciences, professor of the chair for biochemistry and molecular biology with the course of clinical laboratory diagnostics, e-mail: muir@mail.ru

Nosareva О.L. – candidate of medical sciences, associate professor of the chair for biochemistry and molecular biology with the course of clinical laboratory diagnostics, e-mail: olnosareva@yandex.ru

Shakhristova E.V. – candidate of medical sciences, associate professor of the chair for biochemistry and molecular biology with the course of clinical laboratory diagnostics, head of the laboratory of molecular medicine, e-mail: shaxristova@yandex.ru

Ivanov V.V. – candidate of biological sciences, associate professor of the chair for biochemistry and molecular biology with the course of clinical laboratory diagnostics, head of the laboratory for biological models, e-mail: ivanovvv1953@gmail.com