Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain. / Vetrovoy, Oleg; Sarieva, Ksenia; Galkina, Olga; Eschenko, Natalia; Lyanguzov, Andrey; Gluschenko, Tatjana; Tyulkova, Ekaterina; Rybnikova, Elena.
в: Neurochemical Research, Том 44, № 6, 15.06.2019, стр. 1425-1436.Результаты исследований: Научные публикации в периодических изданиях › статья › Рецензирование
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TY - JOUR
T1 - Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain
AU - Vetrovoy, Oleg
AU - Sarieva, Ksenia
AU - Galkina, Olga
AU - Eschenko, Natalia
AU - Lyanguzov, Andrey
AU - Gluschenko, Tatjana
AU - Tyulkova, Ekaterina
AU - Rybnikova, Elena
PY - 2019/6/15
Y1 - 2019/6/15
N2 - Post-conditioning is exposure of an injured organism to the same harmful factors but of milder intensity which mobilizes endogenous protective mechanisms. Recently, we have developed a novel noninvasive post-conditioning (PostC) protocol involving three sequential episodes of mild hypobaric hypoxia which exerts pronounced neuroprotective action. In particular, it prevents development of pathological cascades caused by severe hypobaric hypoxia (SH) such as cellular loss, lipid peroxidation, abnormal neuroendocrine responses and behavioural deficit in experimental animals. Development of these post-hypoxic pathological effects has been associated with the delayed reduction of hypoxia-inducible factor 1 (HIF1) regulatory α-subunit levels in rat hippocampus, whereas PostC up-regulated it. The present study has been aimed at experimental examination of the hypothesis that intrinsic mechanisms underlying the neuroprotective and antioxidant effects of PostC involves HIF1-dependent stimulation of the pentose phosphate pathway (PPP). We have observed that SH leads to a decrease of glucose-6-phosphate dehydrogenase (G6PD) activity in the hippocampus and neocortex of rats as well as to a reduction in NADPH and total glutathione levels. This depletion of the antioxidant defense system together with excessive lipid peroxidation during the reoxygenation phase resulted in increased oxidative stress and massive cellular death observed after SH. In contrast, PostC led to normalization of G6PD activity, stabilization of the NADPH and total glutathione levels and thereby resulted in recovery of the cellular redox state and prevention of neuronal death. Our data suggest that stabilization of the antioxidant system via HIF1-associated PPP regulation represents an important neuroprotective mechanism enabled by PostC.
AB - Post-conditioning is exposure of an injured organism to the same harmful factors but of milder intensity which mobilizes endogenous protective mechanisms. Recently, we have developed a novel noninvasive post-conditioning (PostC) protocol involving three sequential episodes of mild hypobaric hypoxia which exerts pronounced neuroprotective action. In particular, it prevents development of pathological cascades caused by severe hypobaric hypoxia (SH) such as cellular loss, lipid peroxidation, abnormal neuroendocrine responses and behavioural deficit in experimental animals. Development of these post-hypoxic pathological effects has been associated with the delayed reduction of hypoxia-inducible factor 1 (HIF1) regulatory α-subunit levels in rat hippocampus, whereas PostC up-regulated it. The present study has been aimed at experimental examination of the hypothesis that intrinsic mechanisms underlying the neuroprotective and antioxidant effects of PostC involves HIF1-dependent stimulation of the pentose phosphate pathway (PPP). We have observed that SH leads to a decrease of glucose-6-phosphate dehydrogenase (G6PD) activity in the hippocampus and neocortex of rats as well as to a reduction in NADPH and total glutathione levels. This depletion of the antioxidant defense system together with excessive lipid peroxidation during the reoxygenation phase resulted in increased oxidative stress and massive cellular death observed after SH. In contrast, PostC led to normalization of G6PD activity, stabilization of the NADPH and total glutathione levels and thereby resulted in recovery of the cellular redox state and prevention of neuronal death. Our data suggest that stabilization of the antioxidant system via HIF1-associated PPP regulation represents an important neuroprotective mechanism enabled by PostC.
KW - HIF1
KW - Hypoxic post-conditioning
KW - Neuroprotection
KW - Oxidative stress
KW - Pentose phosphate pathway
KW - Severe hypoxia
KW - OXIDATIVE STRESS
KW - SEVERE HYPOBARIC HYPOXIA
KW - REPERFUSION INJURY
KW - ISCHEMIC POSTCONDITIONING PROTECTS
KW - CORTICAL-NEURONS
KW - GLUCOSE-METABOLISM
KW - SIGNALING PATHWAY
KW - HIF-1-ALPHA
KW - EXPRESSION
KW - CEREBRAL ISCHEMIA/REPERFUSION INJURY
UR - http://www.scopus.com/inward/record.url?scp=85056691987&partnerID=8YFLogxK
U2 - 10.1007/s11064-018-2681-x
DO - 10.1007/s11064-018-2681-x
M3 - Article
C2 - 30448928
AN - SCOPUS:85056691987
VL - 44
SP - 1425
EP - 1436
JO - Neurochemical Research
JF - Neurochemical Research
SN - 0364-3190
IS - 6
ER -
ID: 36630429