PFKFB3-mediated glycolysis is involved in reactive astrocyte proliferation after oxygen-glucose deprivation/reperfusion and is regulated by Cdh1
| Autor: | Wenlong Yao, Bo Zhang, Chuanhan Zhang, Jin Qiu, Youyou Lv, Yue Zhang, Chunchun Zhai |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Apc1 Subunit
Anaphase-Promoting Complex-Cyclosome Phosphofructokinase-2 Biology Rats Sprague-Dawley Cellular and Molecular Neuroscience chemistry.chemical_compound medicine Animals Glycolysis Lactic Acid DAPI RNA Small Interfering Cell Proliferation Cell growth Autophagy Cell Biology Transfection Cadherins medicine.disease Cell Hypoxia Rats Proliferating cell nuclear antigen Cell biology Glucose medicine.anatomical_structure chemistry Astrocytes Gene Knockdown Techniques Reperfusion Injury biology.protein Reperfusion injury Astrocyte |
| Zdroj: | Neurochemistry International. 91:26-33 |
| ISSN: | 0197-0186 |
| DOI: | 10.1016/j.neuint.2015.10.006 |
| Popis: | Reactive astrocyte proliferation is involved in many central degenerative diseases. The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase isoform 3 (PFKFB3), an allosteric activator of 6-phosphofructo-1-kinase (PFK1), controls glycolytic flux. Furthermore, APC/C-Cdh1 plays a crucial role in brain metabolism by regulating PFKFB3 expression. Previous studies have defined the roles of PFKFB3-mediated glycolysis in pathological angiogenesis, cell autophagy, and amyloid plaque deposition in proliferating cells. However, the role of PFKFB3 in reactive astrocyte proliferation after cerebral ischemia is unknown. In this study, we cultured rat primary cortical astrocytes and established an oxygen-glucose deprivation/reperfusion (OGD/R) model to mimic cerebral ischemia in vivo. Astrocyte proliferation was measured by western blotting for proliferating cell nuclear antigen (PCNA) and by EdU incorporation. We found that OGD/R up-regulated PFKFB3 and PFK1 expression, which was accompanied by reactive astrocyte proliferation. Knockdown of PFKFB3 by siRNA transfection significantly inhibited reactive astrocyte proliferation and lactate release, an indicator of glycolysis. We found that PFKFB3 and PFK1 expression were down-regulated and lactate release was decreased when OGD/R-induced astrocyte proliferation was inhibited by a Cdh1-expressing lentivirus. Thus, reactive astrocyte proliferation can be effectively suppressed by down-regulation of PFKFB3 through control of glycolytic flux, which is downstream of APC/C-Cdh1. |
| Databáze: | OpenAIRE |
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