ABSTRACT
Oxidative stress is considered to be related to the onset and/or progression of Alzheimer's disease (AD), but there is insufficient evidence of its role(s). In this study, we evaluated the relationships between the brain redox state and cognitive function using a triple transgenic mouse model of AD (3 × Tg-AD mouse). One group of 3 × Tg-AD mice started to receive an α-tocopherol-supplemented diet at 2 months of age and another group of 3 × Tg-AD mice was fed a normal diet. The levels of α-tocopherol, reduced glutathione, oxidized glutathione, and lipid peroxidation were decreased in the cerebral cortex and hippocampus at 4 months of age in the 3 × Tg-AD mice fed a normal diet. These reductions were abrogated by the supplementation of α-tocopherol in the diet. During Morris water maze testing, the 3 × Tg-AD mice did not exhibit cognitive impairment at 4 months of age, but started to show cognitive dysfunction at 6 months of age, and α-tocopherol supplementation suppressed this dysfunction. Magnetic resonance imaging (MRI) using 3-hydroxymethyl-proxyl as a probe showed decreases in the signal intensity in the brains of 3 × Tg-AD mice at 4 months of age, and this reduction was clearly attenuated by α-tocopherol supplementation. Taken together, these findings suggest that oxidative stress can be associated with the cognitive impairment in 3 × Tg-AD mice. Furthermore, MRI might be a powerful tool to noninvasively evaluate the increases in reactive radicals, especially those occurring during the early stages of AD.
Subject(s)
Alzheimer Disease/pathology , Brain/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Magnetic Resonance Imaging , Oxidative Stress , Alzheimer Disease/diagnosis , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/genetics , Animals , Brain/metabolism , Brain/pathology , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/pathology , Disease Models, Animal , Humans , Lipid Peroxidation , Mice , Mice, Transgenic , RadiographyABSTRACT
Oncogenic transformation of mouse C3H10T1/2 cells induced by X-rays was suppressed in the presence of extract of Rooibos tea, Aspalathus linealis. Transformation was reduced with increased concentration of the extract, so that at an extract concentration of 10%, transformation incidence was similar to the spontaneous level. Suppression was also dependent on treatment time with the extract and was maximal when present during the entire incubation period. In contrast, green tea extract at an equitoxic concentration showed no detectable effect on transformation incidence.
Subject(s)
Anticarcinogenic Agents/pharmacology , Cell Transformation, Neoplastic/drug effects , Tea , Animals , Cells, Cultured , Mice , Plant Extracts/pharmacology , X-RaysABSTRACT
On the basis of three-dimensional information, many amino acid substitutions were introduced in the thermostable neutral protease (NprM) of Bacillus stearothermophilus MK232 by site-directed mutagenesis. When Glu at position 143 (Glu-143), which is one of the proposed active sites, was substituted for by Gln and Asp, the proteolytic activity disappeared. F114A (Phe-114 to Ala), Y110W (Tyr-110 to Trp), and Y211W (Tyr-211 to Trp) mutant enzymes had higher activity (1.3- to 1.6-fold) than the wild-type enzyme. When an autolysis site, Tyr-93, was replaced by Gly and Ser, the remaining activities of those mutant enzymes were higher than that of the wild-type enzyme.
