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Title:
Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain | Neurochemical Research
Description:
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 Ξ±-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.
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Keywords {π}
article, pubmed, google, scholar, cas, postconditioning, brain, hypoxia, ischemic, hypoxic, rat, cerebral, pathway, res, rats, zhao, ischemia, central, wang, injury, zhang, research, phosphate, rybnikova, severe, hif, vetrovoy, mechanisms, hypobaric, neurosci, stroke, neurochem, pentose, effects, antioxidant, focal, neuroprotection, neuroprotective, glutathione, oxidative, stress, liu, mol, expression, data, protection, delayed, samoilov, chen, protects,
Topics {βοΈ}
extracellular-signal-regulated kinase signaling month download article/chapter hypoxia inducible factor-1a post-hypoxic pathological effects phosphoinositide-3-kinase/akt pathway regulatory Ξ±-subunit levels mek/erk pathways contribute pi3k-akt signaling pathway noninvasive post-conditioning hypoxia-inducible factor-1alpha ischemic postconditioning-induced neuroprotection mitochondria-controlled signaling mechanisms focal cerebral ischemia/reperfusion saint-petersburg state university pentose phosphate pathway pentose-phosphate pathway full article pdf reporting animal research post-conditioning glutathione-dependent antioxidant system pentose phosphate pathways mild hypobaric hypoxia pathological cascades caused american heart association general neurochemical techniques privacy choices/manage cookies increased oxidative stress ischemia/reperfusion injury ischemia-reperfusion injury hypoxia-inducible factor 1 apoptosis-related proteins pi3k-akt pathway pi3k/akt pathway glucose-6-phosphate dehydrogenase delayed postconditioning protects propofol-induced postconditioning global cerebral ischemia local ethical committee akt/gsk3beta signaling hypoxic preconditioning induces severe hypobaric hypoxia pyruvate dehydrogenase kinase hippocampal field ca1 global brain ischemia hypobaric hypoxic postconditioning hypoxic/ischemic postconditioning focal cerebral ischemia delayed hypoxic postconditioning rat hippocampus caused cellular redox state
Questions {β}
- Scartabelli T, Gerace E, Landucci E, Moroni F, Pellegrini-Giampietro D (2008) Neuroprotection by group I mGlu receptors in a rat hippocampal slice model of cerebral ischemia is associated with the PI3K-Akt signaling pathway: a novel postconditioning strategy?
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headline:Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain
description: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 Ξ±-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.
datePublished:2018-11-17T00:00:00Z
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Severe hypoxia
Hypoxic post-conditioning
HIF1
Pentose phosphate pathway
Oxidative stress
Neuroprotection
Neurosciences
Neurochemistry
Biochemistry
general
Cell Biology
Neurology
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headline:Neuroprotective Mechanism of Hypoxic Post-conditioning Involves HIF1-Associated Regulation of the Pentose Phosphate Pathway in Rat Brain
description: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 Ξ±-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.
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HIF1
Pentose phosphate pathway
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