ИСТИНА

In the brain pentose phosphate pathway (PPP) of glucose metabolism serves as an only source of NADPH which is essential for effective antioxidant defense and prevention of oxidative stress. The key enzyme of this pathway is glucose-6-phosphate dehydrogenase (G6PD). Current work is dedicated to testing the hypothesis about involvement of PPP in implementation of the adaptive brain reactions to hypoxia/reoxygenation and to estimate the role of hypoxia-inducible factor 1 (HIF1) in regulation of PPP and PPP-dependent processes. In mild hypobaric hypoxia (MHH) model there is negative correlation between the amount of HIF1 (immunohistochemical assay) and the level of G6PD mRNA (RT PCR). In model of severe hypobaric hypoxia (SH) the short-term overexpression of HIF1a regulatory subunit is accompanied with decreased activity of G6PD and amount of NADPH (enzymatic colorimetric assays) in CA1 subfield of rat hippocampus. This results in oxidative stress and apoptotic cellular death (TUNEL method). The injection of HIF1 inhibitor topotecan before SH normalizes cellular RedOx status, decreases oxidative damage of macromolecules (Schiff base fluorescent assay) and prevents SH-mediated apoptosis. Current data broaden knowledge about posthypoxic pathology mechanisms. The treatment with HIF1 inhibitors in short-term period after ischemic stroke can be an effective neuroprotective strategy. Scientific research was performed at the Research park of St. Petersburg State University (Observatory of Environmental Safety Center and Center for Molecular and Cell Technologies). The work has been supported by RFBR grants no. 16-34-00027 and 16-04-00987.