Abstract
Control of p53 by histone methylation is closely related in the neuronal apoptosis following ischemic stroke. In mammalian cells, demethylation of methylated lysine residue of histones is catalyzed by Jumonji domain-containing proteins (JMJD) family. Among them, JMJD3 is reported to be a hypoxic target gene and expressed in all cell types of brain including neurons. However, the role of JMJD3 on process of neuronal apoptosis after ischemic stroke is still largely unknown. PCR, immunostaining and Western blotting results indicated that JMJD3 expression was upregulated in cultured neurons upon oxygen–glucose deprivation (OGD) injury. Jmjd3−/− neurons exhibited inhibited cell apoptosis and tolerance to the OGD injury. Chromatin immunoprecipitation and promoter reporter assays showed that the underlying mechanism was through transcriptional activation of p53, thus altering the downstream Bax and Caspase-3 genes. Silencing Jmjd3 improved neurological deficit and reduced infarct volume following ischemic injury in vivo. The present study suggested that JMJD3 was a critical promoter of neuronal apoptosis by regulating the expression of Bax and Caspase-3, and inhibition of JMJD3 might provide a new therapeutic intervention for treating cerebral ischemia.
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