Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments
| Autor: | Yoshikane Izawa, Norihiro Suzuki, Shinichi Takahashi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Glycation End Products
Advanced Time Factors medicine.medical_treatment [14C]deoxyglucose 2-deoxy-d-[1-14C]glucose PERK double-stranded-RNA-dependent protein kinase-like endoplasmic reticulum kinase medicine.disease_cause Ara-C cytosine arabinoside ER (endoplasmic reticulum) stress Pentose Phosphate Pathway Rats Sprague-Dawley pentose phosphate pathway (PPP) chemistry.chemical_compound Pregnancy CMRglc cerebral metabolic rate of glucose DAPI 4′ 6-diamino-2-phenylindole Phosphorylation Cells Cultured Heat-Shock Proteins sulforaphane 1-isothiocyanato-(4R S)-(methylsulfinyl)butane Cerebral Cortex Neurons chemistry.chemical_classification DMEM Dulbecco's modified Eagle's medium General Neuroscience Glutathione PLL poly-l-lysine DBSS Dulbecco's balanced salt solution diabetes mellitus Female 6-AN 6-aminonicotinamide MCB monochlorobimane Oligopeptides Oxidation-Reduction Research Article Calcium Isotopes medicine.medical_specialty S1 NF-E2-Related Factor 2 glucose metabolism PPP pentose phosphate pathway S8 Deoxyglucose Protein Sorting Signals Pentose phosphate pathway Biology Carbohydrate metabolism Nrf2 nuclear factor-erythroid 2 p45 subunit-related factor 2 S5 lcsh:RC321-571 ER endoplasmic reticulum astrocyte H2DCFDA 2′ 7′-dichlorodihydrofluorescein diacetate ROS reactive oxygen species Internal medicine Diabetes mellitus medicine Animals G6PDH glyceraldehyde-6-phosphate dehydrogenase lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry CMRoxy cerebral metabolic rate of oxygen Analysis of Variance Reactive oxygen species BiP immunoglobulin heavy-chain-binding protein Dose-Response Relationship Drug Lysine Endoplasmic reticulum Insulin Hydrogen Peroxide Embryo Mammalian medicine.disease Keap1 Kelch-like enoyl-CoA hydratase-associated protein 1 Rats Glucose Endocrinology AGE advanced glycation end-product Animals Newborn chemistry Astrocytes Neurology (clinical) PFA paraformaldehyde Reactive Oxygen Species Kelch-like enoyl-CoA hydratase-associated protein 1 (Keap1)/nuclear factor-erythroid 2 p45 subunit-related factor 2 (Nrf2) Oxidative stress |
| Zdroj: | ASN Neuro, Vol 4 (2012) ASN NEURO |
| ISSN: | 1759-9091 1759-0914 |
| Popis: | ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke. |
| Databáze: | OpenAIRE |
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