ArticleJournal of molecular neuroscience : MN2020
Pharmacological HIF1 Inhibition Eliminates Downregulation of the Pentose Phosphate Pathway and Prevents Neuronal Apoptosis in Rat Hippocampus Caused by Severe Hypoxia.
Article in Journal of molecular neuroscience : MN, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 33 citations in OpenAlex.
- Impact of hypoxia on the hippocampus: A review.Medicine · 2025Review
- Energy Metabolism Behavior and Response to Microenvironmental Factors of the Experimental Cancer Cell Models Differ from that of Actual Human Tumors.Mini reviews in medicinal chemistry · 2025Review
- Comparative Analysis of the Effects of Maternal Hypoxia and Placental Ischemia on HIF1-Dependent Metabolism and the Glucocorticoid System in the Embryonic and Newborn Rat Brain.International journal of molecular sciences · 2024Article
- Neuroadaptive Biochemical Mechanisms of Remote Ischemic Conditioning.International journal of molecular sciences · 2023Review
- HIF-1α promotes astrocytic production of macrophage migration inhibitory factor following spinal cord injury.CNS neuroscience & therapeutics · 2023Article
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- Roxadustat: Do we know all the answers?Biomolecules & biomedicine · 2023Review
- Protective effects on acute hypoxic-ischemic brain damage in mfat-1 transgenic mice by alleviating neuroinflammation.Journal of biomedical research · 2021Article
- Hypoxia-inducible transcription factor-1α inhibition by topotecan protects against lipopolysaccharide-induced inflammation and apoptosis of cardiomyocytes.Biomedical engineering online · 2021Article
- Pulmonary arterial hypertension induces the release of circulating extracellular vesicles with oxidative content and alters redox and mitochondrial homeostasis in the brains of rats.Hypertension research : official journal of the Japanese Society of Hypertension · 2021Article
- Brain Energy Deficit as a Source of Oxidative Stress in Migraine: A Molecular Basis for Migraine Susceptibility.Neurochemical research · 2021Review
- Glucocorticoid-Dependent Mechanisms of Brain Tolerance to Hypoxia.International journal of molecular sciences · 2021Review
- MicroRNA-489-3p plays a significant role in congenital hypothyroidism through regulating neuronal cell apoptosis via targeting translationally controlled tumor protein 1.Experimental and therapeutic medicine · 2021Article
- Yap-Hippo Signaling Activates Mitochondrial Protection and Sustains Breast Cancer Viability under Hypoxic Stress.Journal of oncology · 2021Article
- Hypoxia-Inducible Factor (HIF) in Ischemic Stroke and Neurodegenerative Disease.Frontiers in cell and developmental biology · 2021Review
- The New CIC Mutation Associates with Mental Retardation and Severity of Seizure in Turkish Child with a Rare Class I Glucose-6-Phosphate Dehydrogenase Deficiency.Journal of molecular neuroscience : MN · 2020Article
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9 authors at 4 institutions in 2 countries.
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Abstract
The pentose phosphate pathway (PPP) of glucose metabolism in the brain serves as a primary source of NADPH which in turn plays a crucial role in multiple cellular processes, including maintenance of redox homeostasis and antioxidant defense. In our model of protective mild hypobaric hypoxia in rats (3MHH), an inverse correlation between hypoxia-inducible factor-1 (HIF1) activity and mRNA levels of glucose-6-phosphate dehydrogenase (G6PD), the key enzyme of PPP, was observed. In the present study, it was demonstrated that severe hypobaric hypoxia (SH) induced short-term upregulation of HIF1 alpha-subunit (HIF1α) in the hippocampal CA1 subfield and decreased the activity of G6PD. The levels of NADPH were also reduced, promoting oxidative stress, triggering apoptosis, and neuronal loss. Injection of a HIF1 inhibitor (HIF1i), topotecan hydrochloride (5 mg/kg, i.p.), before SH prevented the upregulation of HIF1α and normalized G6PD activity. In addition, HIF1i injection caused an increase in NADPH levels, normalization of total glutathione levels and of the cellular redox status as well as suppression of free-radical and apoptotic processes. These results demonstrate a new molecular mechanism of post-hypoxic cerebral pathology development which involves HIF1-dependent PPP depletion and support a recently suggested injurious role of HIF1 activation in the acute phase of cerebral hypoxia/ischemia. Application of PPP stimulators in early post-hypoxic/ischemic period might represent a promising neuroprotective strategy. Graphical abstract HIF1-dependent down-regulation of the pentose phosphate pathway contributes to the hypoxia-induced oxidative stress and neuronal apoptosis in the rat hippocampus.
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