NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of th...NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as well as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.展开更多
Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetyla...Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the Gl-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.展开更多
基金supported by the National Natural Science Foundationof China,No.30800312 and 30970368the Specialized Research Fund for the Doctoral Program of Higher Education,No.20070269026+1 种基金the Fundamental Research Fund for the Central Universities,No.78210020Innovation Program of Shanghai Municipal Education Commission,No.10ZZ35
文摘NR2B subunits are involved in regulating aging, in particular, age-related learning and memory deficits. We examined 19-month-old NR2B transgenic mice and their littermate controls. First, we detected expression of the NR2B subunit gene, Grin2b, in the neocortex of transgenic mice using real-time PCR. Next, we used microarrays to examine differences in neocortical gene expression. Pathway and signal-net analyses identified multiple pathways altered in the transgenic mice, in-cluding the P53, Jak-STAT, Wnt, and Notch pathways, as well as regulation of the actin cytoskeleton and neuroactive ligand-receptor interactions. Further signal-net analysis highlighted the P53 and insulin-like growth factor pathways as key regulatory pathways. Our results provide new insight into understanding the molecular mechanisms of NR2B regulated age-related memory storage, normal organismal aging and age-related disease.
基金supported by the grant from the National High-tech R&D Program(863 Program)(No.2007AA02Z163)the National Natural Science Foundation of China(No. 31000574)the Fundamental Research Fund for the Central Universities(No.78210042)
文摘Butyrate has been recently identified as a natural ligand of the G-protein-coupled receptor 41 （GPR41）. In addition, it is an inhibitor of histone deacetylase （HDAC）. Butyrate treatment results in the hyperacetylation of histones, with resultant multiple biological effects including inhibition of proliferation, induction of cell cycle arrest, and apoptosis, in a variety of cultured mammalian cells. However, it is not clear whether GPR41 is actively involved in the above-mentioned processes. In this study, we generated a stable cell line expressing the hGPR41 receptor in order to investigate the involvement of GPR41 on butyrate-induced biochemical and physiologic processes. We found that GPR41 activation may be a compensatory mechanism to counter the increase in histone H3 acetylation levels induced by butyrate treatment. Moreover, GPR41 had an inhibitory effect on the anti-proliferative, pro-apoptotic effects of butyrate. GPR41 expression induced cell cycle arrest at the Gl-stage, while its activation by butyrate can cause more cells to pass the G1 checkpoint. These results indicated that GPR41 was associated with histone acetylation and might be involved in the acetylation-related regulation of cell processes including proliferation, apoptosis, and the cell cycle.
