Oxidative Stress Accompanies HIF1-DependentImpairment of Glucose Metabolism in theHippocampus of Adult Rats That Survived PrenatalSevere Hypoxia

Vetrovoy, O.; Stratilov, V.; Potapova, S.; Tyulkova, E.

Авторы: Vetrovoy O., Stratilov V., Potapova S., Tyulkova E.
Журнал: Developmental Neuroscience
Год издания: 2023
Издательство: S. Karger AG
Местоположение издательства: Switzerland
DOI: 10.1159/000535326
Аннотация: ntroduction: Many socially significant diseases are associated with prenatal developmental disorders. Previously,we showed the pathological role of hypoxia-induciblefactor-1 (HIF1) in post-hypoxic reoxygenation. Thisstudy aimed to investigate the effect of prenatal severehypoxia (PSH) on HIF1α protein expression as well as onHIF1-dependent activity of the pentose phosphatepathway (PPP) and anaerobic glycolysis in the hippocampus (HPC) of offspring that reached adulthood.Methods: PSH was induced during the critical period offetal hippocampal formation on gestation days 14–16 in ahypobaric chamber (180 Torr, 5% oxygen, 3 h). Subsequent studies were conducted on both the HPC of adultcontrol and PSH rats under normal conditions, as well as inresponse to severe hypoxia (SH) or psycho-emotionalstress (“learned helplessness” [LH] model). We evaluated HIF1α protein levels using both immunohistochemistry and Western blotting techniques. The amountof glucose-6-phosphate dehydrogenase (G6PD) was alsodetermined by Western blotting. Colorimetric enzymaticassays were employed to analyze enzymatic activity oflactate dehydrogenase (LDH), the concentration oflactate, NADPH, reduced glutathione (GSHred), and malonicdialdehyde (MDA). Results: We showed that PSH caused astable increase in the content of HIF1α protein in the HPC,which was accompanied by an increase in the efficiency ofanaerobic glycolysis. This was confirmed by increased LDHactivity and lactate concentration. At the same time, theamounts of G6PD, NADPH, and GSHred decreased in the HPCof PSH rats, whereas the concentration of MDA, an oxidativestress marker, exceeded the control values. In a series ofexperiments using the LH or SH stress, it was shown that inthe HPC of control rats, there was an increase in the amountof HIF1α in response to stress, which was also accompaniedby more efficient anaerobic glycolysis and decrease of PPPdependent NADPH production, similar to the intact PSH rats.In PSH rats, emotional stress resulted in higher HIF1α levelswithout affecting glycolysis or PPP. Conclusion: Therefore, theincreased content and activity of the transcription factorHIF1α in the HPC of adult rats exposed to prenatal hypoxialeads to an imbalance between glycolysis and PPP, which isaccompanied by oxidative stress.
Добавил в систему: Ветровой Олег Васильевич

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Oxidative Stress Accompanies HIF1-DependentImpairment of Glucose Metabolism in theHippocampus of Adult Rats That Survived PrenatalSevere Hypoxiaстатья

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