Activation and polarization of microglia are involved in neuroinflammation and regulate ischemic stroke-associated brain injury. Protein arginine methyltransferase 8 functions as a regulatory component of hypoxic stress-induced neuroinflammation. The protective effect of protein arginine methyltransferase 8 (PRMT8) against ischemic strokeassociated brain injury through regulation of microglia activation and polarization was investigated. First, PRMT8 was downregulated in middle cerebral artery occlusion (MCAO)-induced mice and oxygen−glucose deprivation/reoxygenation (OGD/R)-induced SH-SY5Y. Injection with AAV-PRMT8 reduced infarct volumes in MCAO-induced mice. Moreover, injection with AAV-PRMT8 promoted neuronal survival and ameliorated histopathological changes in the brains of MCAO-induced mice. The neuronal apoptosis and neuroinflammation in MCAO-induced mice were suppressed by AAV-PRMT8 injection. Second, PRMT8 overexpression increased cell viability and suppressed the cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. Third, injection with AAV-PRMT8 reduced almost 50% of CD86 + M1 microglia and enhanced about 20% of CD206 + M2 microglia. Furthermore, PRMT8 overexpression attenuated OGD/R-induced M1 phenotype polarization of BV2. Lastly, PRMT8 upregulated Lin28a and loss of Lin28a attenuated PRMT8 overexpression-induced increase in cell viability and decrease in cell apoptosis and inflammation of OGD/R-induced SH-SY5Y. In conclusion, PRMT8 promoted M2 phenotype polarization of microglia and suppressed neuronal apoptosis to ameliorate cerebral ischemia/reperfusion injury through upregulation of Lin28a.
In this study, the estrogenic effect of GL-1, a component of the Ganoderma lucidum, was studied, and the possible mechanism was discussed preliminarily. The binding ability of GL-1 to estrogen receptor was calculated by computer-aided simulation. The effects of GL-1 on the proliferation of estrogen sensitive estrogen receptor (ER) (+) MCF-7 cells and estrogen insensitive ER (-) MDA-MB-231 cells were detected by MTT method. The effects of GL-1 on the proliferation of estrogen-induced MCF-7 cells, and the effects of the estrogen receptor inhibitor ICI182780 on the proliferation of GL-1-induced MCF-7 cells were detected by MTT assay. The expression of ERα and ERβ monoclonal antibody were detected by Western blot. The results showed that GL-1 has a good binding ability to estrogen receptor β, and has estrogen-like effect, which might be related to secretion of estrogen and expression of ERβ by binding to ERs.
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