ABSTRACT
The learning and memory impairment of presenilin 2 transgenic mice was mentioned previously. In this study, exposing the presenilin 2 transfected PC12 cells to the 50 microM Abeta(25-35), 30 mM l-glutamate and 50 microM H(2)O(2) resulted in significant increase 8-oxodG and p53 levels of the cells expressing the mutant gene. The increase was also found in the mutant presenilin 2 transgenic mice brains age-dependently in comparison to that in the wild-type presenilin 2-transgenic mice and non-transgenic ones. These findings indicated that mutant presenilin 2 clearly increases oxidative stress and p53 expression, which could be implicated in promoting mutant presenilin 2-induced neurodegeneration in Alzheimer's disease, and the influence of mutant presenilin 2 in Alzheimer's disease may be brain regional and age related effects.
Subject(s)
Alzheimer Disease/metabolism , Neurons/metabolism , Presenilin-2/metabolism , Tumor Suppressor Protein p53/metabolism , Animals , Mutation , Oxidative Stress , PC12 Cells , Presenilin-2/genetics , RatsABSTRACT
Mutation in the presenilin 2 (PS2mt) is known to be one of factors involved in the development of Alzheimer's disease (AD). It was recently revealed that an abnormality of lipid metabolism is a phenomenon occurring in AD. Therefore, the aim of this study was to investigate the potential relationship between the mutation of PS2 and alterations of the lipid profile within the brain. The results showed there increases in the levels of cholesterol, low density lipoprotein and triglyceride, but a decrease in the level of high density lipoprotein in brain tissues expressing mutant PS2. These findings indicated that PS2mt is involved in the abnormalities of the lipid profile, which could cause or result in the development of AD.
Subject(s)
Alzheimer Disease/metabolism , Brain/metabolism , Cholesterol/metabolism , Lipoproteins/metabolism , Mutation/genetics , Presenilin-2/genetics , Age Factors , Alzheimer Disease/genetics , Animals , Cholesterol, HDL/metabolism , Cholesterol, LDL/metabolism , Colorimetry/methods , Lipid Metabolism , Mice , Mice, Transgenic , Triglycerides/metabolismABSTRACT
A presenilin 2 mutation is believed to be involved in the development of Alzheimer's disease. In addition, transgenic mice with a presenilin 2 mutation have been reported to have learning and memory impairments. In this study, exposing PC12 cells expressing mutant presenilin 2 to 50 microM AP25-35, 30 mM L-glutamate and 50 microM H2O2 caused a significant increase in acetylcholine esterase activity. An in vivo study revealed high levels of this enzyme activity in the mutant presenilin 2 transgenic brains compared with the wild type presenilin 2 transgenic and nontransgenic samples. These results suggest that a mutant presenilin 2-induced neurodegeneration in Alzheimer's disease might be involved in the increase in acetylcholinesterase activity. These findings might help in the development of an appropriate therapeutic intervention targeting mutant presenilin 2-induced Alzheimer's disease.
Subject(s)
Acetylcholinesterase/metabolism , Membrane Proteins/physiology , Mutation , Neurons/enzymology , Alzheimer Disease/drug therapy , Alzheimer Disease/enzymology , Alzheimer Disease/etiology , Animals , Brain/enzymology , Membrane Proteins/genetics , Mice , Mice, Transgenic , PC12 Cells , Presenilin-2 , RatsABSTRACT
Decreases in activities of the NF-kappaB, AP-1 and SP-1 transcription factors, which could act as antiapoptotic factors, in the presenilin 2 transfected PC12 cells, either in nontreatment conditions or under apoptotic stimulation, were found in this study. Similar results were also found in mice brain cells carrying presenilin 2, especially in the mutant gene expressed ones. These findings suggested that presenilin 2 may be implicated in neuronal cell death by altering the antiapoptotic activity of the transcription factors.
