ABSTRACT
KDM5B is a histone H3K4me2/3 demethylase. The PHD1 domain of KDM5B is critical for demethylation, but the mechanism underlying the action of this domain is unclear. In this paper, we observed that PHD1KDM5B interacts with unmethylated H3K4me0. Our NMR structure of PHD1KDM5B in complex with H3K4me0 revealed that the binding mode is slightly different from that of other reported PHD fingers. The disruption of this interaction by double mutations on the residues in the interface (L325A/D328A) decreases the H3K4me2/3 demethylation activity of KDM5B in cells by approximately 50% and increases the transcriptional repression of tumor suppressor genes by approximately twofold. These findings imply that PHD1KDM5B may help maintain KDM5B at target genes to mediate the demethylation activities of KDM5B.
Subject(s)
Humans , Binding Sites , Genetics , Crystallography, X-Ray , Gene Expression Regulation , HEK293 Cells , Histones , Chemistry , Metabolism , Jumonji Domain-Containing Histone Demethylases , Chemistry , Genetics , Metabolism , Lysine , Chemistry , Metabolism , Magnetic Resonance Spectroscopy , Methylation , Microscopy, Fluorescence , Models, Molecular , Mutation , Nuclear Proteins , Chemistry , Genetics , Metabolism , Peptides , Chemistry , Genetics , Metabolism , Protein Binding , Protein Structure, Tertiary , Repressor Proteins , Chemistry , Genetics , MetabolismABSTRACT
@#ObjectiveTo explore the effect of Yinaotongluo Capsule on diffuse weighting image and enenery metabolism of ischemia-reperfuing rat.MethodsMagnetic resonance diffusion-weighted imaging(DWI) and 1H and magnetic resonance spectroscopy(MRS) were performed in different brain regions in focal cerebral ischemic-reperfusion injury model rats. ResultsYinaotongluo Capsule could significantly reduce the area and the intensity of infarction of rats by DWI 3 h and 5 d after treatment compared with the model group.The result of 1H MRS examination demonstrated Lac peak was lower and NAA peak higher than that of the model group. ConclusionYinaotongluo Capsule can effectually improve enenery metabolism during cerebral ischemia and reperfuing, so that to reduce the neuronal dysfunction and death in infarcts at the late stage.
ABSTRACT
Objective To study the biochemical alterations in rat brain under chronic cerebral ischemia by means of 1H and 31 P magnetic resonance spectroscopy (MRS) Methods Chronic cerebral ischemia was induced by permanent bilateral commom carotid artery occlusion (2 VO)in the regions of the hippocampal CA1 area and the whole brain. Results In vivo 1H MRS did not reveal any significant change in the concentrations of N acetyl aspartate (NAA) and Lactate (Lac) in the hippocampal CA1 region 31 P MRS in the whole brain showed an elevation of phosphomonoesters (PME). The ratio of PME/(PME+PDE) was 0 54?0 03 in sham group and 0 69?0 02 in 2 VO group ( P