The Effect of Hypoxia Preconditioning on DNA Methyltransferase and PP1γ in Hippocampus of Hypoxia Preconditioned Mice

Abstract

Abstract

Zhang, Shu, Yanbo Zhang, Shuyuan Jiang, You Liu, Lihua Huang, Tao Zhang, Guowei Lu, Kerui Gong, Xunming Ji, and Guo Shao. The effect of hypoxia preconditioning on DNA methyltransferase and PP1γ in hippocampus of hypoxia preconditioned mice. High Alt Med Biol 15:483–490, 2014.—It is well known that hypoxia preconditioning can increase hypoxic tolerance by changing the expressions of some genes in the brain. DNA methylation is important for regulating gene expression and is catalyzed by DNA methyltransferase (DNMT), an enzyme that is abundant in the brain. However, the impact of hypoxia preconditioning on DNA methylation remains unknown. In the current study, mice were randomly divided into three groups: blank control group with no exposure to hypoxia (H0), the hypoxia control group exposed to hypoxia once (H1), and the hypoxia preconditioning group exposed to 4 runs of hypoxia (H4). The mRNA and protein levels of three kinds of DNMTs and the activity of total DMNT were measured. Protein phosphatase 1(PP1)γ, which critically regulates neuroprotective pathways in brain, was measured in mRNA and protein activity and promoter methylation. DNMT1 was unchanged in H1 and H4, while DNMT3A and DNMT3B were decreased in H4. The mRNA and protein levels of PP1γ were decreased in H4. However, there was no detectable change in the level of DNA methylation of the promoter of PP1γ (-321 bp to 95 bp). These findings suggest that DNA methylation may have a role in hypoxia neuroprotection, and the change of PP1γ, which did not depend on the change of its promoter (-321 bp to 95bp) DNA methylation, may be involved in neuroprotection.