ArticleMolecular neurobiology2021
Phosphoenolpyruvate Carboxykinase (PCK) in the Brain Gluconeogenic Pathway Contributes to Oxidative and Lactic Injury After Stroke.
Article in Molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 35 citations in OpenAlex.
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- Critical role of translocator protein (TSPO) in neuronal mitochondrial dysfunction and mental stress-exacerbated ischemic injury following stroke.Translational psychiatry · 2025Article
- Transcriptional analysis of cancer cachexia: conserved and unique features across preclinical models and biological sex.American journal of physiology. Cell physiology · 2024Article
- Phosphoenolpyruvate induces endothelial dysfunction and cell senescence through stimulation of metabolic reprogramming.Journal of bioenergetics and biomembranes · 2023Article
- Cerebral Glucose Metabolism and Potential Effects on Endoplasmic Reticulum Stress in Stroke.Aging and disease · 2023Review
- Exercise postconditioning reduces ischemic injury via suppression of cerebral gluconeogenesis in rats.Brain and behavior · 2023Article
- The potential role of T-cell metabolism-related molecules in chronic neuropathic pain after nerve injury: a narrative review.Frontiers in immunology · 2023Review
- Metabolomic analysis and pharmacological validation of the cerebral protective effect of 3,4‑dihydroxybenzaldehyde on cerebral ischemia‑reperfusion injury.Molecular medicine reports · 2023Article
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- Human iPSC-derived cerebral organoids model features of Leigh syndrome and reveal abnormal corticogenesis.Development (Cambridge, England) · 2022Article
- Neuroprotective Effects of Pharmacological Hypothermia on Hyperglycolysis and Gluconeogenesis in Rats after Ischemic Stroke.Biomolecules · 2022Article
- Role of Forkhead Box Protein O1 (FoxO1) in Stroke: A Literature Review.Aging and disease · 2022Review
- Chicoric Acid Prevents Neuroinflammation and Neurodegeneration in a Mouse Parkinson's Disease Model: Immune Response and Transcriptome Profile of the Spleen and Colon.International journal of molecular sciences · 2022Article
- Phosphoenolpyruvate carboxykinase in cell metabolism: Roles and mechanisms beyond gluconeogenesis.Molecular metabolism · 2021Review
- Perspectives on benefit of early and prereperfusion hypothermia by pharmacological approach in stroke.Brain circulationReview
- Retrospective Evaluation of Acid-Base Disorders in Dogs With Hyperlactatemia Using Traditional and Semiquantitative Analysis: 3866 Cases.Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001)Article
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
To demonstrate the role of the rate-limiting and ATP-dependent gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PCK) in oxidative and lactic stress and the effect of phenothiazine on PCK after stroke, a total of 168 adult male Sprague Dawley rats (3 months old, 280-300 g) underwent 2-h intraluminal middle cerebral artery occlusion (MCAO) and reperfusion for 6, 24, 48 h, or 7 days. Phenothiazine (chlorpromazine and promethazine (C+P)) (8 mg/kg) and 3-mercaptopicolinic acid (3-MPA, a PCK inhibitor, 100 μM) were administered at reperfusion onset. The effects of phosphoenolpyruvate, 3-MPA, or PCK knockdown were studied in neuronal cultures subjected to oxygen/glucose deprivation. Reactive oxygen species, lactate, phosphoenolpyruvate (PEP; a gluconeogenic product), mRNA, and protein of total PCK, PCK-1, and PCK-2 increased after MCAO and oxygen-glucose deprivation (OGD). Oxaloacetate (a gluconeogenic substrate) decreased, while PEP and glucose were increased, suggesting reactive gluconeogenesis. These changes were attenuated by phenothiazine, 3-MPA, or PCK shRNA. PCK-1 and -2 existed primarily in neurons, while the effects of ischemic stroke on the PCK expression were seen predominately in astrocytes. Thus, phenothiazine reduced infarction and oxidative/lactic stress by inhibiting PCKs, leading to functional recovery.
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