Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Melatonin demonstrates neuroprotective properties in adult models of cerebral ischemia, acting as a potent antioxidant and anti-inflammatory agent. We investigated the effect of melatonin in a 7-d-old rat model of ischemia-reperfusion, leading to both cortical infarct and injury in the underlying white matter observed using MRI and immunohistochemistry. Melatonin was given i.p. as either a single dose before ischemia or a double-dose regimen, combining one before ischemia and one 24 h after reperfusion. At 48 h after injury, neither a significant reduction in cortical infarct volume nor a variation in the number of TUNEL- and nitrotyrosine-positive cells within the ipsilateral lesion was observed in melatonin-treated animals compared with controls. However, a decrease in the density of tomato lectin-positive cells after melatonin treatment was found in the white matter underlying cortical lesion. Furthermore, we showed a marked increase in the myelin basic protein-immunoreactivity in the cingulum and in the density of mature oligodendrocytes (APC-immunoreactive) in both the ipsilateral cingulum and external capsule. These results suggest that melatonin is not able to reduce cortical infarct volume in a neonatal stroke model but strongly reduces inflammation and promotes subsequent myelination in the white matter.
 ...
PMID:Melatonin promotes myelination by decreasing white matter inflammation after neonatal stroke. 2085 66

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.
 ...
PMID:PFKFB3-mediated glycolysis is involved in reactive astrocyte proliferation after oxygen-glucose deprivation/reperfusion and is regulated by Cdh1. 2649 54