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Inhibition of 2-OxoglutarateDehydrogenase as a Chemical Model of Acute Hypobaric Hypoxiaстатья
Статья опубликована в высокорейтинговом журнале
Статья опубликована в журнале из списка Web of Science и/или Scopus- Авторы: Graf A., Ksenofontov A., Bunik V.
- Журнал: Frontiers in Medicine
- Том: 8
- Год издания: 2021
- Первая страница: 1
- Последняя страница: 10
- Номер статьи: 751639
- DOI: 10.3389/fmed.2021.751639
- Аннотация: Both hypoxia and inhibition of 2-oxoglutarate dehydrogenase complex (OGDHC) areknown to change cellular amino acid pools, but the quantitative comparison of themetabolic and physiological outcomes has not been done. We hypothesize that OGDHCinhibition models metabolic changes caused by hypoxia, as both perturb the respiratorychain function, limiting either the NADH (OGDHC inhibition) or oxygen (hypoxia) supply.In the current study, we quantify the changes in the amino acid metabolism afterOGDHC inhibition in the highly sensitive to hypoxia cerebellum and compare themto the earlier characterized changes after acute hypobaric hypoxia. In addition, theassociated physiological effects are characterized and compared. A specific OGDHCinhibitor succinyl phosphonate (SP) is shown to act similar to hypoxia, increasing levelsof many amino acids in the cerebellum of non-pregnant rats, without affecting thosein the pregnant rats. Compared with hypoxia, stronger effects of SP in non-pregnantrats are observed on the levels of cerebellar amino acids, electrocardiography (ECG),and freezing time. In pregnant rats, hypoxia affects ECG and behavior more than SP,although none of the stressors significantly change the levels of cerebellar amino acids.The biochemical differences underlying the different physiological actions of SP andhypoxia are revealed by correlation analysis of the studied parameters. The negativecorrelations of cerebellar amino acids with OGDHC and/or tryptophan, shown to ariseafter the action of SP and hypoxia, discriminate the overall metabolic action of thestressors. More negative correlations are induced in the non-pregnant rats by hypoxia,and in the pregnant rats by SP. Thus, our findings indicate that the OGDHC inhibitionmimics the action of acute hypobaric hypoxia on the cerebellar amino acid levels, but abetter prediction of the physiological outcomes requires assessment of integral networkchanges,suchasincreasesinthenegativecorrelationsamongtheaminoacids,OGDHC,and/or tryptophan.
- Добавил в систему: Ксенофонтов Александр Леонидович